Differential Regulation of Clusterin Isoforms by the Androgen Receptor

Clusterin (CLU) was initially reported as an androgen-repressed gene which is now shown to be an androgen-regulated ATP-independent cytoprotective molecular chaperone. CLU binds to a wide variety of client proteins to potently inhibit stress-induced protein aggregation and chaperone or stabilise conformations of proteins at times of cell stress. CLU is an enigmatic protein, being ascribed both pro- and anti-apoptotic roles. Recent evidence has shown that both secreted (sCLU) and nuclear (nCLU) isoforms can be produced, and that protein function is dependent on the sub-cellular localisation. We and others have shown that sCLU is cytoprotective, while nCLU is pro-apoptotic. It now seems likely that the apparently dichotomous functions of CLU result from the expression of different but related CLU isoforms and splice variants, and that cell survival depends in part on the relative expression of pro- versus anti-apoptotic CLU proteins. In cancer cells, increased sCLU expression is associated with increased resistance to apoptotic triggers and treatment resistance. CLU is a stress-induced protein upregulated after apoptotic triggers like androgen ablation and chemotherapy. Treatment strategies targeting stress-associated increases in sCLU expression enhance treatment-induced apoptosis and delay the emergence of androgen independence. Differential regulation of CLU isoforms and splice variants by androgens may be a pathway whereby cancer cells develop treatment resistance and evade apoptosis.

Enhanced geoproof : improved geographic assurance for data in the cloud

The geographic location of cloud data storage centres is an important issue for many organisations and individuals due to various regulations that require data and operations to reside in specific geographic locations. Thus, cloud users may want to be sure that their stored data have not been relocated into unknown geographic regions that may compromise the security of their stored data. Albeshri et al. (2012) combined proof of storage (POS) protocols with distance-bounding protocols to address this problem. However, their scheme involves unnecessary delay when utilising typical POS schemes due to computational overhead at the server side. The aim of this paper is to improve the basic GeoProof protocol by reducing the computation overhead at the server side. We show how this can maintain the same level of security while achieving more accurate geographic assurance.

An efficient proactive route maintenance process for reliable data transmissions in sensor networks

For industrial wireless sensor networks, maintaining the routing path for a high packet delivery ratio is one of the key objectives in network operations. It is important to both provide the high data delivery rate at the sink node and guarantee a timely delivery of the data packet at the sink node. Most proactive routing protocols for sensor networks are based on simple periodic updates to distribute the routing information. A faulty link causes packet loss and retransmission at the source until periodic route update packets are issued and the link has been identified as broken. We propose a new proactive route maintenance process where periodic update is backed-up with a secondary layer of local updates repeating with shorter periods for timely discovery of broken links. Proposed route maintenance scheme improves reliability of the network by decreasing the packet loss due to delayed identification of broken links. We show by simulation that proposed mechanism behaves better than the existing popular routing protocols (AODV, AOMDV and DSDV) in terms of end-to-end delay, routing overhead, packet reception ratio.

First aid treatment of burn injuries

The recommendations for the first aid treatment of burn injuries have previously been based upon conflicting published studies and as a result the recommendations have been vague with respect to optimal first aid treatment modality, temperature, duration and delay after which treatment is still effective. The public have also continued to use treatments such as ice and alternative therapies, however there is little evidence to support their use. Recently there have been several studies conducted by burn researchers in Australia which have enabled the recommendations to be clarified. First aid should consist of cool running water (2-15°C), applied for 20 minutes duration, as soon as possible but for up to 3 hours after the burn injury has occurred. Ice should not be used and alternative therapies should only be used to relieve pain as an adjunct to cold water treatment. Optimal first aid treatment significantly reduces tissue damage, hastens wound re-epithelialisation and reduces scarring and should be promoted widely to the public.

Olfactory glia enhance neonatal axon regeneration

Olfactory ensheathing cells (OECs) migrate with olfactory axons that extend from the nasal epithelium into the olfactory bulb. Unlike other glia, OECs are thought to migrate ahead of growing axons instead of following defined axonal paths. However it remains unknown how the presence of axons and OECs influences the growth and migration of each other during regeneration. We have developed a regeneration model in neonatal mice to examine whether (i) the presence of OECs ahead of olfactory axons affects axonal growth and (ii) the presence of olfactory axons alters the distribution of OECs. We performed unilateral bulbectomy to ablate olfactory axons followed by methimazole administration to further delay neuronal growth. In this model OECs filled the cavity left by the bulbectomy before new axons extended into the cavity. We found that delaying axon growth increased the rate at which OECs filled the cavity. The axons subsequently grew over a significantly larger region and formed more distinct fascicles and glomeruli in comparison with growth in animals that had undergone only bulbectomy. In vitro, we confirmed (i) that olfactory axon growth was more rapid when OECs were more widely distributed than the axons and (ii) that OECs migrated faster in the absence of axons. These results demonstrate that the distribution of OECs can be increased by repressing by growth of olfactory axons and that olfactory axon growth is significantly enhanced if a permissive OEC environment is present prior to axon growth.

Web based surveillance systems could improve disease detection and the response to emerging disease events

The Chinese government should be commended for its open, concerted, and rapid response to the recent H7N9 influenza outbreak. However, the first known case was not reported until 48 days after disease onset.1 Although the difficulties in detecting the virus and the lack of suitable diagnostic methods have been the focus of discussion,2 systematic limitations that may have contributed to this delay have hardly been discussed. The detection speed of surveillance systems is limited by the highly structured nature of information flow and hierarchical organisation of these systems. Flu surveillance usually relies on notification to a central authority of laboratory confirmed cases or presentations to sentinel practices for flu-like illness. Each step in this pathway presents a bottleneck at which information and time can be lost; this limitation must be dealt with...

Engraftment outcomes after HPC co-culture with mesenchymal stromal cells and osteoblasts

Haematopoietic stem cell (HSC) transplantation is an established cell-based therapy for a number of haematological diseases. To enhance this therapy, there is considerable interest in expanding HSCs in artificial niches prior to transplantation. This study compared murine HSC expansion supported through co-culture on monolayers of either undifferentiated mesenchymal stromal cells (MSCs) or osteoblasts. Sorted Lineage− Sca-1+ c-kit+ (LSK) haematopoietic stem/progenitor cells (HPC) demonstrated proliferative capacity on both stromal monolayers with the greatest expansion of LSK shown in cultures supported by osteoblast monolayers. After transplantation, both types of bulk-expanded cultures were capable of engrafting and repopulating lethally irradiated primary and secondary murine recipients. LSKs co-cultured on MSCs showed comparable, but not superior, reconstitution ability to that of freshly isolated LSKs. Surprisingly, however, osteoblast co-cultured LSKs showed significantly poorer haematopoietic reconstitution compared to LSKs co-cultured on MSCs, likely due to a delay in short-term reconstitution. We demonstrated that stromal monolayers can be used to maintain, but not expand, functional HSCs without a need for additional haematopoietic growth factors. We also demonstrated that despite apparently superior in vitro performance, co-injection of bulk cultures of osteoblasts and LSKs in vivo was detrimental to recipient survival and should be avoided in translation to clinical practice.

Ozone-induced dissociation of conjugated lipids reveals significant reaction rate enhancements and characteristic odd-electron product ions

Ozone-induced dissociation (OzID) is an alternative ion activation method that relies on the gas phase ion-molecule reaction between a mass-selected target ion and ozone in an ion trap mass spectrometer. Herein, we evaluated the performance of OzID for both the structural elucidation and selective detection of conjugated carbon-carbon double bond motifs within lipids. The relative reactivity trends for \[M + X](+) ions (where X = Li, Na, K) formed via electrospray ionization (ESI) of conjugated versus nonconjugated fatty acid methyl esters (FAMEs) were examined using two different OzID-enabled linear ion-trap mass spectrometers. Compared with nonconjugated analogues, FAMEs derived from conjugated linoleic acids were found to react up to 200 times faster and to yield characteristic radical cations. The significantly enhanced reactivity of conjugated isomers means that OzID product ions can be observed without invoking a reaction delay in the experimental sequence (i.e., trapping of ions in the presence of ozone is not required). This possibility has been exploited to undertake neutral-loss scans on a triple quadrupole mass spectrometer targeting characteristic OzID transitions. Such analyses reveal the presence of conjugated double bonds in lipids extracted from selected foodstuffs. Finally, by benchmarking of the absolute ozone concentration inside the ion trap, second order rate constants for the gas phase reactions between unsaturated organic ions and ozone were obtained. These results demonstrate a significant influence of the adducting metal on reaction rate constants in the fashion Li > Na > K.

Tracking-based moving object detection

We present a novel approach for multi-object detection in aerial videos based on tracking. The proposed method mainly involves three steps. Firstly, the spatial-temporal saliency is employed to detect moving objects. Secondly, the detected objects are tracked by mean shift in the subsequent frames. Finally, the saliency results are fused with the weight map generated by tracking to get refined detection results, and in turn the modified detection results are used to update the tracking models. The proposed algorithm is evaluated on VIVID aerial videos, and the results show that our approach can reliably detect moving objects even in challenging situations. Meanwhile, the proposed method can process videos in real time, without the effect of time delay.

Intake rigour : ensuring only “reportable deaths” become coroners’ cases

The failure of medical practitioners to consistently discharge their obligation to report sudden or unnatural deaths to coroners has rightly prompted concern. Following recent public scandals, coroners and health authorities have increasingly developed procedures to ensure that concerning deaths are reported to coroners. However, the negative consequences of deaths being unnecessarily reported have received less attention: unnecessary intrusion into bereavement; a waste of public resources; and added delay and hindrance to the investigation of matters needing a coroner’s attention. Traditionally, coroners have largely, unquestioningly assumed jurisdiction over any deaths for which a medical practitioner has not issued a cause of death certificate. The Office of the State Coroner in Queensland has recently trialled a system to more rigorously assess whether deaths apparently resulting from natural causes, which have been reported to a coroner, should be investigated by the coroner, rather than being finalised by a doctor issuing a cause of death certificate. This article describes that trial and its results.

Accurate placement of a pelvic binder improves reduction of unstable fractures of the pelvic ring

The aim of this study was to assess the accuracy of placement of pelvic binders and to determine whether circumferential compression at the level of the greater trochanters is the best method of reducing a symphyseal diastasis. Patients were identified by a retrospective review of all pelvic radiographs performed at a military hospital over a period of 30 months. We analysed any pelvic radiograph on which the buckle of the pelvic binder was clearly visible. The patients were divided into groups according to the position of the buckle in relation to the greater trochanters: high, trochanteric or low. Reduction of the symphyseal diastasis was measured in a subgroup of patients with an open-book fracture, which consisted of an injury to the symphysis and disruption of the posterior pelvic arch (AO/OTA 61-B/C). We identified 172 radiographs with a visible pelvic binder. Five cases were excluded due to inadequate radiographs. In 83 (50%) the binder was positioned at the level of the greater trochanters. A high position was the most common site of inaccurate placement, occurring in 65 (39%). Seventeen patients were identified as a subgroup to assess the effect of the position of the binder on reduction of the diastasis. The mean gap was 2.8 times greater (mean difference 22 mm) in the high group compared with the trochanteric group (p < 0.01). Application of a pelvic binder above the level of the greater trochanters is common and is an inadequate method of reducing pelvic fractures and is likely to delay cardiovascular recovery in these seriously injured patients.

Expanding Emergency Department capacity : a multisite study

Objectives: To i) identify predictors of admission, and ii) describe outcomes for patients who arrived via ambulance to three Australian public Emergency Departments (EDs), before and after the opening of 41 additional ED beds within the area. Methods: A retrospective, comparative, cohort study using deterministically linked health data collected between 3 September 2006 and 2 September 2008. Data included ambulance offload delay, time to see doctor, ED length of stay (ED LOS), admission requirement, access block, hospital length of stay and in-hospital mortality. Logistic regression analysis was undertaken to identify predictors of hospital admission. Results: One third of all 286,037 ED presentations were via ambulance (n= 79,196) and 40.3% required admission. After increasing emergency capacity, the only outcome measure to improve was in-hospital mortality. Ambulance offload delay, time to see doctor, ED length of stay (ED LOS), admission requirement, access block, hospital length of stay did not improve. Strong predictors of admission before and after increased capacity included: age over 65 years, Australian Triage Scale (ATS) category 1-3, diagnoses of circulatory or respiratory conditions and ED LOS > 4 hours. With additional capacity the odds ratios for these predictors increased for age >65 and ED LOS > 4 hours and decreased for triage category and ED diagnoses. Conclusions: Expanding ED capacity from 81 to 122 beds within a health service area impacted favourably on mortality outcomes but not on time-related service outcomes such as ambulance offload time, time to see doctor and ED LOS. To improve all service outcomes, when altering (increasing/decreasing) ED bed numbers, the whole healthcare system needs to be considered.

Crushed tablets : does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted.

Motor Accident Insurance Act 1994 s45 - whether obligation to co-operate may authorise order requiring commencement of proceedings by minor prior to expiration of limitation period

In Australian Associated Motor Insurers Ltd v McPaul; Council of the City of Gold Coast v McPaul [2005] QSC 278 the applicant insurer sought an order requiring a claimant who had been injured in a motor vehicle accident some years earlier when he was five years old to commence a proceeding to determine the question of the applicant's liability to him. The applicant's interest in seeking the order was to avoid the prejudice which could follow from further delay, particularly delay until the respondent became obliged to commence proceedings to avoid a limitations bar.

The development of an intervention to promote the capacity to wait in children with intellectual disability

Aim: Individuals with intellectual disability (ID) often have difficulty with waiting, an important aspect of everyday life. Successful waiting require cognitive, emotional and behavioural self-regulation, and is an essential element in the capacity to delay gratification. Method: We developed an intervention to provide parents with the knowledge and strategies to promote their child’s capacity to wait. The intervention was grounded in previous work about the skills underpinning successful waiting, such as goal-setting, understanding time, and managing frustration. Eleven parents of children with ID (mean CA 9.4 years; mean MA 47 months) participated in an intervention trial. Following pre-testing of their child’s capacity to wait and delay gratification, parents attended a 1 day workshop that was followed by monthly phone discussions with the researchers to monitor progress and provide advice. Post-testing was undertaken 1 year later. Results: Compared with a wait-listed control group, children whose parents had completed the intervention displayed significant improvements in their capacity to wait on a delay of gratification task. Parents reported that their child had become more successful in everyday waiting situations. Conclusion: The results of this pilot study are promising and pave the way for larger-scale interventions to improve self-regulatory skills in people with ID.