'Hero to healing' drink driving program for Indigenous communities in Far North Queensland

Issue addressed: Alcohol-related road crashes are a leading cause of the injury burden experienced by Indigenous Australians. Existing drink driving programs are primarily designed for the mainstream population. The ‘Hero to Healing’ program was specifically developed with Indigenous communities and is underpinned by the Community Reinforcement Approach (CRA). This paper reports on the formative evaluation of the program from delivery in two Far North Queensland communities. Methods: Focus groups and semistructured interviews were conducted with drink driver participants (n = 17) and other Elders and community members (n = 8) after each program. Qualitative content analysis was used to categorise the transcripts. Results: The CRA appealed to participants because of its flexible nature and encouragement of rearranging lifestyle factors, without specific focus on alcohol use. Participants readily identified with the social and peer-related risk and protective factors discussed. Cofacilitation of the program with Elders was identified as a key aspect of the program. More in-depth discussion about cannabis and driving, anger management skills and relationship issues are recommended. Conclusions: Participants’ recognition of content reinforced earlier project results, particularly the use of kinship pressure to motivate younger family members to drink drive. Study findings suggest that the principles of the CRA are useful; however, some amendments to the CRA components and program content were necessary. So what?: Treating drink driving in regional and remote Indigenous Australian communities as a community and social issue, rather than an individual phenomenon, is likely to lead to a reduction in the number of road-related injuries Indigenous people experience.

ACE Research Vignette #52: Business growth and new initiatives in small and medium manufacturing enterprises from a design innovation program

This series of research vignettes is aimed at sharing current and interesting research findings from our team of international Entrepreneurship researchers. This vignette, written by Dr Judy Matthews examines the effects of firm engagement with design innovation programs on entrepreneurial activities of small and medium enterprises.

Screening for partner violence among family mediation clients: Differentiating types of abuse

Family mediation is mandated in Australia for couples in dispute over separation and parenting as a first step in dispute resolution, except where there is a history of intimate partner violence. However, validation of effective well-differentiated partner violence screening instruments suitable for mediation settings is at an early phase of development. This study contributes to calls for better violence screening instruments in the mediation context to detect a differentiated range of abusive behaviors by examining the reliability and validity of both established scales, and newly developed scales that measured intimate partner violence by partner and by self. The study also aimed to examine relationships between types of abuse, and between gender and types of abuse. A third aim was to examine associations between types of abuse and other relationship indicators such as acrimony and parenting alliance. The data reported here are part of a larger mixed method, naturalistic longitudinal study of clients attending nine family mediation centers in Victoria, Australia. The current analyses on baseline cross-sectional screening data confirmed the reliability of three subscales of the Conflict Tactics Scale (CTS2), and the reliability and validity of three new scales measuring intimidation, controlling and jealous behavior, and financial control. Most clients disclosed a history of at least one type of violence by partner: 95% reported psychological aggression, 72% controlling and jealous behavior, 50% financial control, and 35% physical assault. Higher rates of abuse perpetration were reported by partner versus by self, and gender differences were identified. There were strong associations between certain patterns of psychologically abusive behavior and both acrimony and parenting alliance. The implications for family mediation services and future research are discussed.

Guided respiration mindfulness therapy: Development and evaluation of a brief therapist training program

The present paper describes the development and evaluation of a standardized multi-component therapist training program in guided respiration mindfulness therapy (GRMT). GMRT is a manual-based, experimental clinical intervention involving concentrated focus on sustained self-regulation of breathing, application of mindfulness to emergent somatic experience and relaxation. Therapists (n = 61) new to the approach attended a 2-day experiential workshop and were evaluated pre-post workshop for change in intervention knowledge, as well as change in mindfulness. These trainees also participated in post-workshop focus group sessions to explore perception of the intervention. A subset of 40 therapists participated in a second training component, and 14 of these were rated for competent delivery of the intervention during participation in a clinical trial. During training, therapists personally received the treatment giving the opportunity to assess treatment session (n = 283) impact on sense of wellbeing. Results indicated a brief focused training program can equip therapists with basic knowledge and skills required to deliver the standardized manual-based treatment. Qualitative analysis of focus group sessions showed that therapists endorsed the intervention for clinical use and found it personally beneficial. This research provides a foundation for further evaluation of clinical effectiveness of the intervention.

Making sense of a trial maths intervention program for teachers of students with disability in Australia: Interim report

The Disability Standards for Education (2005) and the Australian Curriculum, Assessment and Reporting Authority relevant standards underscore the right of students with disability to access the curriculum on the same basis as students without disability. Students with disability are entitled to rigorous, relevant and engaging learning opportunities drawn from the Australian curriculum content. Taking this context into account, this paper provides a work-in-progress report on a two-year mathematics intervention project conducted in 12 special schools (Preparatory-Year 12) in Queensland, Australia. The project aims to build the capacity of teachers to teach mathematics to their students and to identify and make sense of the intervention program’s impact. It combines two approaches—appreciative inquiry and action research to monitor schools’ change processes. The interim findings demonstrated that teachers were concerned about their students’ underachievement in mathematics and that the multi-sensory forms of teaching advocated in the program increased student engagement and performance.

Mass spectrometry and n-in-one analytics in early drug discovery: Combinatorial chemistry libraries, lipophilicity and absorption screening

This thesis describes current and past n-in-one methods and presents three early experimental studies using mass spectrometry and the triple quadrupole instrument on the application of n-in-one in drug discovery. N-in-one strategy pools and mix samples in drug discovery prior to measurement or analysis. This allows the most promising compounds to be rapidly identified and then analysed. Nowadays properties of drugs are characterised earlier and in parallel with pharmacological efficacy. Studies presented here use in vitro methods as caco-2 cells and immobilized artificial membrane chromatography for drug absorption and lipophilicity measurements. The high sensitivity and selectivity of liquid chromatography mass spectrometry are especially important for new analytical methods using n-in-one. In the first study, the fragmentation patterns of ten nitrophenoxy benzoate compounds, serial homology, were characterised and the presence of the compounds was determined in a combinatorial library. The influence of one or two nitro substituents and the alkyl chain length of methyl to pentyl on collision-induced fragmentation was studied, and interesting structurefragmentation relationships were detected. Two nitro group compounds increased fragmentation compared to one nitro group, whereas less fragmentation was noted in molecules with a longer alkyl chain. The most abundant product ions were nitrophenoxy ions, which were also tested in the precursor ion screening of the combinatorial library. In the second study, the immobilized artificial membrane chromatographic method was transferred from ultraviolet detection to mass spectrometric analysis and a new method was developed. Mass spectra were scanned and the chromatographic retention of compounds was analysed using extract ion chromatograms. When changing detectors and buffers and including n-in-one in the method, the results showed good correlation. Finally, the results demonstrated that mass spectrometric detection with gradient elution can provide a rapid and convenient n-in-one method for ranking the lipophilic properties of several structurally diverse compounds simultaneously. In the final study, a new method was developed for caco-2 samples. Compounds were separated by liquid chromatography and quantified by selected reaction monitoring using mass spectrometry. This method was used for caco-2 samples, where absorption of ten chemically and physiologically different compounds was screened using both single and nin- one approaches. These three studies used mass spectrometry for compound identification, method transfer and quantitation in the area of mixture analysis. Different mass spectrometric scanning modes for the triple quadrupole instrument were used in each method. Early drug discovery with n-in-one is area where mass spectrometric analysis, its possibilities and proper use, is especially important.

11β-Hydroxysteroid dehydrogenase inhibitors and selectivity modeling of 11β-HSDs

11β-hydroksisteroididehydrogenaasientsyymit (11β-HSD) 1 ja 2 säätelevät kortisonin ja kortisolin määrää kudoksissa. 11β-HSD1 -entsyymin ylimäärä erityisesti viskeraalisessa rasvakudoksessa aiheuttaa metaboliseen oireyhtymän klassisia oireita, mikä tarjoaa mahdollisuuden metabolisen oireyhtymän hoitoon 11β-HSD1 -entsyymin selektiivisellä estämisellä. 11β-HSD2 -entsyymin inhibitio aiheuttaa kortisonivälitteisen mineralokortikoidireseptorien aktivoitumisen, mikä puolestaan johtaa hypertensiivisiin haittavaikutuksiin. Haittavaikutuksista huolimatta 11β-HSD2 -entsyymin estäminen saattaa olla hyödyllistä tilanteissa, joissa halutaan nostaa kortisolin määrä elimistössä. Lukuisia selektiivisiä 11β-HSD1 inhibiittoreita on kehitetty, mutta 11β-HSD2-inhibiittoreita on raportoitu vähemmän. Ero näiden kahden isotsyymin aktiivisen kohdan välillä on myös tuntematon, mikä vaikeuttaa selektiivisten inhibiittoreiden kehittämistä kummallekin entsyymille. Tällä työllä oli kaksi tarkoitusta: (1) löytää ero 11β-HSD entsyymien välillä ja (2) kehittää farmakoforimalli, jota voitaisiin käyttää selektiivisten 11β-HSD2 -inhibiittoreiden virtuaaliseulontaan. Ongelmaa lähestyttiin tietokoneavusteisesti: homologimallinnuksella, pienmolekyylien telakoinnilla proteiiniin, ligandipohjaisella farmakoforimallinnuksella ja virtuaaliseulonnalla. Homologimallinnukseen käytettiin SwissModeler -ohjelmaa, ja luotu malli oli hyvin päällekäinaseteltavissa niin templaattinsa (17β-HSD1) kuin 11β-HSD1 -entsyymin kanssa. Eroa entsyymien välillä ei löytynyt tarkastelemalla päällekäinaseteltuja entsyymejä. Seitsemän yhdistettä, joista kuusi on 11β-HSD2 -selektiivisiä, telakoitiin molempiin entsyymeihin käyttäen ohjelmaa GOLD. 11β-HSD1 -entsyymiin yhdisteet kiinnittyivät kuten suurin osa 11β-HSD1 -selektiivisistä tai epäselektiivisistä inhibiittoreista, kun taas 11β-HSD2 -entsyymiin kaikki yhdisteet olivat telakoituneet käänteisesti. Tällainen sitoutumistapa mahdollistaa vetysidokset Ser310:een ja Asn171:een, aminohappoihin, jotka olivat nähtävissä vain 11β-HSD2 -entsyymissä. Farmakoforimallinnukseen käytettiin ohjelmaa LigandScout3.0, jolla ajettiin myös virtuaaliseulonnat. Luodut kaksi farmakoforimallia, jotka perustuivat aiemmin telakointiinkin käytettyihin kuuteen 11β-HSD2 -selektiiviseen yhdisteeseen, koostuivat kuudesta ominaisuudesta (vetysidosakseptori, vetysidosdonori ja hydrofobinen), ja kieltoalueista. 11β-HSD2 -selektiivisyyden kannalta tärkeimmät ominaisuudet ovat vetysidosakseptori, joka voi muodostaa sidoksen Ser310 kanssa ja vetysidosdonori sen vieressä. Tälle vetysidosdonorille ei löytynyt vuorovaikutusparia 11β-HSD2-mallista. Sopivasti proteiiniin orientoitunut vesimolekyyli voisi kuitenkin olla sopiva ratkaisu puuttuvalle vuorovaikutusparille. Koska molemmat farmakoforimallit löysivät 11β-HSD2 -selektiivisiä yhdisteitä ja jättivät epäselektiivisiä pois testiseulonnassa, käytettiin molempia malleja Innsbruckin yliopistossa säilytettävistä yhdisteistä (2700 kappaletta) koostetun tietokannan seulontaan. Molemmista seulonnoista löytyneistä hiteistä valittiin yhteensä kymmenen kappaletta, jotka lähetettiin biologisiin testeihin. Biologisien testien tulokset vahvistavat lopullisesti sen kuinka hyvin luodut mallit edustavat todellisuudessa 11β-HSD2 -selektiivisyyttä.

A new ELISA plate based microtiter well assay for mycobacterial topoisomerase I for the direct screening of enzyme inhibitory monoclonal antibody supernatants

Antigen specific monoclonal antibodies present in crude hybridoma supernatants are normally screened by ELISA on plates coated with the relevant antigen. Screening for inhibitory monoclonals to enzymes would require the evaluation of purified antibodies or antibody containing supernatants for their inhibition of enzyme activity in a separate assay. However, screening for inhibitory antibodies against DNA transacting enzymes such as topoisomerase I (topo I) cannot be done using hybridoma supernatants due to the presence of nucleases in tissue culture media containing foetal calf serum which degrade the DNA substrates upon addition. We have developed a simple and rapid screening procedure for the identification of clones that secrete inhibitory antibodies against mycobacterial topo I using 96 well ELISA microtiter plates. The principle of the method is the selective capture of monoclonal antibodies from crude hybridoma supernatants by topo I that is tethered to the plate through the use of plate-bound polyclonal anti-topo I antibodies. This step allows the nucleases present in the medium to be washed off leaving the inhibitor bound to the tethered enzyme. The inhibitory activity of the captured antibody is assessed by performing an in situ DNA relaxation assay by the addition of supercoiled DNA substrate directly to the microtiter well followed by the analysis of the reaction products by agarose gel electrophoresis. The validity of this method was confirmed by purification of the identified inhibitory antibody and its evaluation in a DNA relaxation assay. Elimination of all enzyme-inhibitory constituents of the culture medium from the well in which the inhibitory antibody is bound to the tethered enzyme may make this method broadly applicable to enzymes such as DNA gyrases, restriction enzymes and other DNA transaction enzymes. Further, the method is simple and avoids the need of prior antibody purification for testing its inhibitory activity. (C) 2010 Elsevier B.V. All rights reserved.

Screening Cycles

We demonstrate how endogenous information acquisition in credit markets creates lending cycles when competing banks undertake their screening decisions in an uncoordinated way, thereby highlighting the role of intertemporal screening externalities induced by lending market competition as a structural source of instability. We show that uncoordinated screening behavior of competing banks may be not only the source of an important financial multiplier, but also an independent source of fluctuations inducing business cycles. The screening cycle mechanism is robust to generalizations along many dimensions such as the lending market structure, the lending rate determination and the imperfections in the screening technology.

A novel two sources ultrasound modulated optical tomographic system for screening breast cancer through elasticity characterization

The study of non-invasive characterization of elastic properties of soft biological tissues has been a focus of active researches since recent years. Light is highly scattered by biological tissues and hence, sophisticated reconstruction algorithms are required to achieve good imaging depth and a reasonable resolution. Ultrasound (US), on the otherhand, is less scattered by soft tissues and it has been in use for imaging in biomedical ultrasound systems. Combination of the contrast sensitivity of light and good localization of ultrasound provides a challenging technique for characterization of thicker tissues deep inside the body non-invasively. The elasticity of the tissues is characterized by studying the response of tissues to mechanical excitation induced by an acoustic radiation force (remotely) using an optical laser. The US modulated optical signals which traverse the tissue are detected by using a CCD camera as detector array and the pixel map formed on the CCD is used to characterize the embedded inhomogeneities. The use of CCD camera improves the signal-noise-ratio (SNR) by averaging the signals from all of the CCD pixels.

Neonatal screening for amino acidaemias in Karnataka, south India

Consanguineous marriages are strongly favoured among the peoples of South India. Because of the potential genetic risks resulting from inbreeding, a neonatal screening project was established in 1980 in the state of Karnataka for the identification of amino acidaemias. To date, blood samples obtained by toe-stab from 98,256 neonates have been tested by thin layer chromatography, with 46 single and 70 general amino acidaemias detected. The coefficients of inbreeding (F) for the two groups of neonates were 0.0336 and 0.0350, by comparison with a previously determined F value for the general, new-born population of 0.0298. The most common single abnormality detected was tyrosinaemia, with spontaneous resolution in the majority of cases.

Introduction of high-content screening method for studying drug-induced mitochondrial dysfunction in hepatocytes

Drug induced liver injury is one of the frequent reasons for the drug removal from the market. During the recent years there has been a pressure to develop more cost efficient, faster and easier ways to investigate drug-induced toxicity in order to recognize hepatotoxic drugs in the earlier phases of drug development. High Content Screening (HCS) instrument is an automated microscope equipped with image analysis software. It makes the image analysis faster and decreases the risk for an error caused by a person by analyzing the images always in the same way. Because the amount of drug and time needed in the analysis are smaller and multiple parameters can be analyzed from the same cells, the method should be more sensitive, effective and cheaper than the conventional assays in cytotoxicity testing. Liver cells are rich in mitochondria and many drugs target their toxicity to hepatocyte mitochondria. Mitochondria produce the majority of the ATP in the cell through oxidative phosphorylation. They maintain biochemical homeostasis in the cell and participate in cell death. Mitochondria is divided into two compartments by inner and outer mitochondrial membranes. The oxidative phosphorylation happens in the inner mitochondrial membrane. A part of the respiratory chain, a protein called cytochrome c, activates caspase cascades when released. This leads to apoptosis. The aim of this study was to implement, optimize and compare mitochondrial toxicity HCS assays in live cells and fixed cells in two cellular models: human HepG2 hepatoma cell line and rat primary hepatocytes. Three different hepato- and mitochondriatoxic drugs (staurosporine, rotenone and tolcapone) were used. Cells were treated with the drugs, incubated with the fluorescent probes and then the images were analyzed using Cellomics ArrayScan VTI reader. Finally the results obtained after optimizing methods were compared to each other and to the results of the conventional cytotoxicity assays, ATP and LDH measurements. After optimization the live cell method and rat primary hepatocytes were selected to be used in the experiments. Staurosporine was the most toxic of the three drugs and caused most damage to the cells most quickly. Rotenone was not that toxic, but the results were more reproducible and thus it would serve as a good positive control in the screening. Tolcapone was the least toxic. So far the conventional analysis of cytotoxicity worked better than the HCS methods. More optimization needs to be done to get the HCS method more sensitive. This was not possible in this study due to time limit.

A microcomputer program to analyze the CD spectrum of proteins and nucleic acids—Use of LOTUS 1-2-3 spread sheet

A user friendly interactive computer program, CIRDIC, is developed which calculates the molar ellipticity and molar circular dichroic absorption coefficients from the CD spectrum. This, in combination with LOTUS 1-2-3 spread sheet, will give the spectra of above parameters vs wavelength. The code is implemented in MicroSoft FORTRAN 77 which runs on any IBM compatible PC under MSDOS environment.

Development of a structured program for conversion to prenex normal form

The method of structured programming or program development using a top-down, stepwise refinement technique provides a systematic approach for the development of programs of considerable complexity. The aim of this paper is to present the philosophy of structured programming through a case study of a nonnumeric programming task. The problem of converting a well-formed formula in first-order logic into prenex normal form is considered. The program has been coded in the programming language PASCAL and implemented on a DEC-10 system. The program has about 500 lines of code and comprises 11 procedures.