Multifunctional and multitargeted nanoparticles for drug delivery to overcome barriers of drug resistance in human cancers

The recurrence and metastatic spread of cancer are major drawbacks in cancer treatment. Although chemotherapy is one of the most effective methods for the treatment of metastatic cancers, it is nonspecific and causes significant toxic damage. The development of drug resistance to chemotherapeutic agents through various mechanisms also limits their therapeutic potential. However, as we discuss here, the use of nanodelivery systems that are a combination of diagnostics and therapeutics (theranostics) is as relatively novel concept in the treatment of cancer. Such systems are likely to improve the therapeutic benefits of encapsulated drugs and can transit to the desired site, maintaining their pharmaceutical properties. The specific targeting of malignant cells using multifunctional nanoparticles exploits theranostics as an improved agent for delivering anticancer drugs and as a new solution for overriding drug resistance.

Expert systems modeling for assessing climate change impacts and adaptation in agricultural systems at regional level

Australian agriculture is very susceptible to the adverse impacts of climate change, with major shifts in temperature and rainfall projected. In this context, this paper describes a research methodology for assessing potential climate change impacts on, and formulating adaptation options for, agriculture at regional level. The methodology was developed and applied in the analysis of climate change impacts on key horticultural commodities—pome fruits (apples and pears), stone fruits (peaches and nectarines) and wine grapes—in the Goulburn Broken catchment management region, State of Victoria, Australia. Core components of the methodology are mathematical models that enable to spatially represent the degree of biophysical land suitability for the growth of agricultural commodities in the region of interest given current and future climatic conditions. The methodology provides a sound analytic approach to 1) recognise regions under threat of declines in agricultural production due to unfolding climatic changes; 2) identify alternative agricultural systems better adapted to likely future climatic conditions and 3) investigate incremental and transformational adaptation actions to improve the problem situations that are being created by climate change.

Internet content regulation, public drug websites and the growth in hidden Internet services

Governments have traditionally censored drug-related information, both in traditional media and, in recent years, in online media. We explore Internet content regulation from a drug-policy perspective by describing the likely impacts of censoring drug websites and the parallel growth in hidden Internet services. Australia proposes a compulsory Internet filtering regime that would block websites that ‘depict, express or otherwise deal with matters of… drug misuse or addiction’ and/or ‘promote, incite or instruct in matters of crime’. In this article, we present findings from a mixed-methods study of online drug discussion. Our research found that websites dealing with drugs, that would likely be blocked by the filter, in fact contributed positively to harm reduction. Such sites helped people access more comprehensive and relevant information than was available elsewhere. Blocking these websites would likely drive drug discussion underground at a time when corporate-controlled ‘walled gardens’ (e.g. Facebook) and proprietary operating systems on mobile devices may also limit open drug discussion. At the same time, hidden Internet services, such as Silk Road, have emerged that are not affected by Internet filtering. The inability for any government to regulate Tor websites and the crypto-currency Bitcoin poses a unique challenge to drug prohibition policies.
Read More: http://informahealthcare.com/doi/full/10.3109/09687637.2012.745828

Protecting and promoting mental health in the workplace : developing a systems approach to job stress

Issue addressed: Job stress has been linked to a wide range of adverse effects on mental, physical, and organisational health. Despite the evidence that systems approaches are most effective in reducing the adverse impact of job stress, prevalent practice is dominated by worker- or individual-focused strategies in the absence of commensurate intervention on working conditions. Methods: A literature review and cross-disciplinary conceptual synthesis were combined in the articulation of a systems approach to job stress. Results: An outline of the job stress process is followed by explanation of how a systems approach addresses the various steps in the stress process. Systems approaches to job stress emphasise primary prevention or focusing on stressors as the upstream determinants of job stress. Additionally, systems approaches integrate primary with worker-directed secondary and illness-directed tertiary intervention, include the meaningful participation of groups targeted by intervention, and are context- sensitive. Systems approach intervention principles are illustrated by concrete examples of intervention strategies and activities. Conclusions: Further efforts are needed to promote, disseminate, implement, and evaluate systems approaches to job stress and to improve cross-disciplinary cooperation in this effort. (author abtract)

Protecting and promoting mental health in the workplace: developing a systems approach to job stress

Issue addressed: Job stress has been linked to a wide range of adverse effects on mental, physical, and organisational health. Despite the evidence that systems approaches are most effective in reducing the adverse impact of job stress, prevalent practice is dominated by worker- or individual-focused strategies in the absence of commensurate intervention on working conditions. Methods: A literature review and cross-disciplinary conceptual synthesis were combined in the articulation of a systems approach to job stress. Results: An outline of the job stress process is followed by explanation of how a systems approach addresses the various steps in the stress process. Systems approaches to job stress emphasise primary prevention or focusing on stressors as the upstream determinants of job stress. Additionally, systems approaches integrate primary with worker-directed secondary and illness-directed tertiary intervention, include the meaningful participation of groups targeted by intervention, and are context- sensitive. Systems approach intervention principles are illustrated by concrete examples of intervention strategies and activities. Conclusions: Further efforts are needed to promote, disseminate, implement, and evaluate systems approaches to job stress and to improve cross-disciplinary cooperation in this effort.

Historical antecedents shaping corporate reporting in Iran

This research paper examines the evolution of corporate reporting and governance in Iran over the last century. The approach adopted was to provide an historical perspective to examine the environment within which Iranian corporate reporting has emerged and been shaped. An historical framework allows the study to focus on the evolution and development of corporate reporting practice in Iran. By adopting an historical framework, this study is able to inform future research based on models that adopt an evolutionary approach to the assessment of environmental factors on economic systems. The conclusion reached in this study is that socio-economic and political changes during the century have been opportune as drivers of corporate reporting in Iran. The study makes an incremental contribution to the existing accounting history literature for Asia / Middle East / developing countries.

A strain-promoted alkyne-azide cycloaddition (SPAAC) reaction of a novel EpCAM aptamer-fluorescent conjugate for imaging of cancer cells

For the first time, a novel EpCAM aptamer (SYL3C)-DIBO-AF594 fluorescent conjugate was synthesised by bioorthogonal chemistry utilizing a strain promoted alkyne-azide cycloaddition (copper free click) reaction (SPAAC). The ligation efficiency of SPAAC was improved by freeze-thaw cycles. The obtained conjugate showed target specific binding and aided in the imaging of various EpCAM positive cancer cell lines like MCF7, MDAMB453, Weri-RB1 and PC3.

Fraud, market reaction, and the role of institutional investors in Chinese listed firms

The extent and type of financial fraud committed by listed firms in China, stock market reaction to the detection and announcement of fraud, and the association between institutional ownership and financial fraud are the subjects of this article. Using fraud data from the period between 2001 and 2011, the authors find wide occurrences of fraud and a strong negative market reaction on the announcement date, particularly in cases of serious fraud. Fraud is more likely to occur at firms that have a smaller proportion of independent directors and at poorly performing firms. Firms with higher mutual fund ownership subsequently have fewer incidences of fraud. Our results reports by the authors indicate that ownership by independent institutions, such as mutual funds, serves as an effective monitoring mechanism, deterring fraud and enhancing corporate governance in Chinese capital markets.

RAFT controlled synthesis of graphene/polymer hydrogel with enhanced mechanical property for pH-controlled drug release

A pH-sensitive, mechanically strong and thermally stable graphene/poly (acrylic acid) (graphene/PAA) hydrogel was prepared via reversible addition fragmentation transfer (RAFT) polymerizations in the presence of a cross-linking agent. The RAFT agent was covalently coupled onto graphene basal planes via an esterification reaction, with benzoic acid functionalities pre-attached on graphene with its aryl diazonium salt precursor. AFM and SEM analysis revealed the successful preparation of single layered graphene sheets and graphene/polymer hydrogels with pH controlled porous structures. Attenuated total reflection infrared (ATR-IR) and thermogravimetric analyzer (TGA) verified the successful stepwise preparation of graphene/PAA hydrogel. This graphene/PAA hydrogel was pH-sensitive and more mechanically elastic than the PAA hydrogel prepared without graphene. The pH sensitivity of the hydrogel was further utilized for controlled drug release. Doxorubicin was chosen as a model drug and loaded into the hydrogels. The drug loading and release experiment indicated that this hydrogel can be used to efficiently control drug release in the intestine environment (pH = 7.4), better than release in a more acidic environment.© 2013 Elsevier Ltd. All rights reserved.

Young adult sequelae of adolescent cannabis use: an integrative analysis

 Background: Debate continues about the consequences of adolescent cannabis use. Existing data are limited in statistical power to examine rarer outcomes and less common, heavier patterns of cannabis use than those already investigated; furthermore, evidence has a piecemeal approach to reporting of young adult sequelae. We aimed to provide a broad picture of the psychosocial sequelae of adolescent cannabis use. Methods: We integrated participant-level data from three large, long-running longitudinal studies from Australia and New Zealand: the Australian Temperament Project, the Christchurch Health and Development Study, and the Victorian Adolescent Health Cohort Study. We investigated the association between the maximum frequency of cannabis use before age 17 years (never, less than monthly, monthly or more, weekly or more, or daily) and seven developmental outcomes assessed up to age 30 years (high-school completion, attainment of university degree, cannabis dependence, use of other illicit drugs, suicide attempt, depression, and welfare dependence). The number of participants varied by outcome (N=2537 to N=3765). Findings: We recorded clear and consistent associations and dose-response relations between the frequency of adolescent cannabis use and all adverse young adult outcomes. After covariate adjustment, compared with individuals who had never used cannabis, those who were daily users before age 17 years had clear reductions in the odds of high-school completion (adjusted odds ratio 0·37, 95% CI 0·20-0·66) and degree attainment (0·38, 0·22-0·66), and substantially increased odds of later cannabis dependence (17·95, 9·44-34·12), use of other illicit drugs (7·80, 4·46-13·63), and suicide attempt (6·83, 2·04-22·90). Interpretation: Adverse sequelae of adolescent cannabis use are wide ranging and extend into young adulthood. Prevention or delay of cannabis use in adolescence is likely to have broad health and social benefits. Efforts to reform cannabis legislation should be carefully assessed to ensure they reduce adolescent cannabis use and prevent potentially adverse developmental effects. Funding: Australian Government National Health and Medical Research Council. © 2014 Elsevier Ltd.

Implementation of an audit with feedback knowledge translation intervention to promote medication error reporting in health care: a protocol.

BACKGROUND: Health professionals strive to deliver high-quality care in an inherently complex and error-prone environment. Underreporting of medical errors challenges attempts to understand causative factors and impedes efforts to implement preventive strategies. Audit with feedback is a knowledge translation strategy that has potential to modify health professionals' medical error reporting behaviour. However, evidence regarding which aspects of this complex, multi-dimensional intervention work best is lacking. The aims of the Safe Medication Audit Reporting Translation (SMART) study are to: 1. Implement and refine a reporting mechanism to feed audit data on medication errors back to nurses 2. Test the feedback reporting mechanism to determine its utility and effect 3. Identify characteristics of organisational context associated with error reporting in response to feedback METHODS/DESIGN: A quasi-experimental design, incorporating two pairs of matched wards at an acute care hospital, is used. Randomisation occurs at the ward level; one ward from each pair is randomised to receive the intervention. A key stakeholder reference group informs the design and delivery of the feedback intervention. Nurses on the intervention wards receive the feedback intervention (feedback of analysed audit data) on a quarterly basis for 12 months. Data for the feedback intervention come from medication documentation point-prevalence audits and weekly reports on routinely collected medication error data. Weekly reports on these data are obtained for the control wards. A controlled interrupted time series analysis is used to evaluate the effect of the feedback intervention. Self-report data are also collected from nurses on all four wards at baseline and at completion of the intervention to elicit their perceptions of the work context. Additionally, following each feedback cycle, nurses on the intervention wards are invited to complete a survey to evaluate the feedback and to establish their intentions to change their reporting behaviour. To assess sustainability of the intervention, at 6 months following completion of the intervention a point-prevalence chart audit is undertaken and a report of routinely collected medication errors for the previous 6 months is obtained. This intervention will have wider application for delivery of feedback to promote behaviour change for other areas of preventable error and adverse events.

Advances in molecular genetic systems in malaria

Robust tools for analysing gene function in Plasmodium parasites, which are the causative agents of malaria, are being developed at an accelerating rate. Two decades after genetic technologies for use in Plasmodium spp. were first described, a range of genetic tools are now available. These include conditional systems that can regulate gene expression at the genome, transcriptional or protein level, as well as more sophisticated tools for gene editing that use piggyBac transposases, integrases, zinc-finger nucleases or the CRISPR-Cas9 system. In this Review, we discuss the molecular genetic systems that are currently available for use in Plasmodium falciparum and Plasmodium berghei, and evaluate the advantages and limitations of these tools. We examine the insights that have been gained into the function of genes that are important during the blood stages of the parasites, which may help to guide the development and improvement of drug therapies and vaccines.

The missing evidence: a systematic review of patients' experiences of adverse events in health care

PURPOSE: Preventable patient harm due to adverse events (AEs) is a significant health problem today facing contemporary health care. Knowledge of patients' experiences of AEs is critical to improving health care safety and quality. A systematic review of studies of patients' experiences of AEs was conducted to report their experiences, knowledge gaps and any challenges encountered when capturing patient experience data. DATA SOURCES: Key words, synonyms and subject headings were used to search eight electronic databases from January 2000 to February 2015, in addition to hand-searching of reference lists and relevant journals. STUDY SELECTION: Titles and abstracts of publications were screened by two reviewers and checked by a third. Full-text articles were screened against the eligibility criteria. DATA EXTRACTION: Data on design, methods and key findings were extracted and collated. RESULTS: Thirty-three publications demonstrated patients identifying a range of problems in their care; most commonly identified were medication errors, communication and coordination of care problems. Patients' income, education, health burden and marital status influence likelihood of reporting. Patients report distress after an AE, often exacerbated by receiving inadequate information about the cause. Investigating patients' experiences is hampered by the lack of large representative patient samples, data over sufficient time periods and varying definitions of an AE. CONCLUSION: Despite the emergence of policy initiatives to enhance patient engagement, few studies report patients' experiences of AEs. This information must be routinely captured and utilized to develop effective, patient-centred and system-wide policies to minimize and manage AEs.

The effect of a staged, emergency department specific rapid response system on reporting of clinical deterioration

BACKGROUND: Despite emerging evidence regarding clinical deterioration in emergency department (ED) patients, the widespread uptake of rapid response systems (RRS) in EDs has been limited. AIMS: To evaluate the effect of an ED RRS on reporting of clinical deterioration and determine if there were differences between patients who did, and did not, deteriorate during ED care. METHODS: A retrospective cross sectional design was used to conduct this single site study in Melbourne, Australia. Stratified random sampling identified 50 patients with shortness of breath, chest pain or abdominal pain per each year studied (2009-2012) giving a total of 600 patients. The intervention was an ED RRS implemented in stages. RESULTS: The frequency of clinical deterioration was 14.8% (318 episodes/89 patients). Unreported deterioration decreased each year (86.7%; 68.8%; 55.3%; 54.0%, p=0.141). Patients who deteriorated during ED care had a longer median ED length of stay (2.8h; p<0.001), were 31.9% more likely to need hospital admission (p<0.001) and 4.9% more likely to die in hospital (p=0.044). CONCLUSIONS: A staged ED specific RRS decreased the frequency of unreported clinical deterioration. Controlled multi-site studies of ED specific RRSs are needed to examine the effect of formal ED RRSs on patient outcomes.

Chemiluminescence detection of MDMA in street drug samples using tris (2,2'-bipyridine) ruthenium (III)

Tris(2,2'-bipyridine)ruthenium(II) chemiluminescence was investigated for the detection of 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds in street drug samples. Optimization using flow injection analysis showed that the selectivity of the reagent can be targeted towards the detection of secondary amines by altering the pH of the reaction environment. The greater selectivity of this mode of detection, compared to UV-absorbance, reduces the probability of false positive results from interfering compounds. The detection limit for MDMA under these conditions was 0.48 μM. A HPLC method incorporating post-column tris(2,2'-bipyridine)ruthenium(II) chemiluminescence detection was applied to the determination of MDMA in five street drug samples. The results obtained were in good agreement with quantification performed using traditional UV-absorbance detection, which demonstrates the viability of this method for confirmatory analysis of drug samples. This is the first report of tris(2,2'-bipyridine)ruthenium(II) chemiluminescence for the detection of MDMA and related amphetamine derivatives.