Principals of audit: Testing, data and ‘implicated advocacy’

Historically, school leaders have occupied a somewhat ambiguous position within networks of power. On the one hand, they appear to be celebrated as what Ball (2003) has termed the ‘new hero of educational reform'; on the other, they are often ‘held to account’ through those same performative processes and technologies. These have become compelling in schools and principals are ‘doubly bound’ through this. Adopting a Foucauldian notion of discursive production, this paper addresses the ways that the discursive ‘field’ of ‘principal’ (within larger regimes of truth such as schools, leadership, quality and efficiency) is produced. It explores how individual principals understand their roles and ethics within those practices of audit emerging in school governance, and how their self-regulation is constituted through NAPLAN – the National Assessment Program, Literacy and Numeracy. A key effect of NAPLAN has been the rise of auditing practices that change how education is valued. Open-ended interviews with 13 primary and secondary school principals from Western Australia, South Australia and New South Wales asked how they perceived NAPLAN's impact on their work, their relationships within their school community and their ethical practice.

Surface Proteins of Lactobacillus crispatus: Adhesive Properties and Cell Wall Anchoring

Bacterial surface-associated proteins are important in communication with the environment and bacteria-host interactions. In this thesis work, surface molecules of Lactobacillus crispatus important in host interaction were studied. The L. crispatus strains of the study were known from previous studies to be efficient in adhesion to intestinal tract and ECM. L. crispatus JCM 5810 possess an adhesive surface layer (S-layer) protein, whose functions and domain structure was characterized. We cloned two S-layer protein genes (cbsA; collagen-binding S-layer protein A and silent cbsB) and identified the protein region in CbsA important for adhesion to host tissues, for polymerization into a periodic layer as well as for attachment to the bacterial cell surface. The analysis was done by extensive mutation analysis and by testing His6-tagged fusion proteins from recombinant Escherichia coli as well as by expressing truncated CbsA peptides on the surface of Lactobacillus casei. The N-terminal region (31-274) of CbsA showed efficient and specific binding to collagens, laminin and extracellular matrix on tissue sections of chicken intestine. The N-terminal region also contained the information for formation of periodic S-layer polymer. This region is bordered at both ends by a conserved short region rich in valines, whose substitution to leucines drastically affected the periodic polymer structure. The mutated CbsA proteins that failed to form a periodic polymer, did not bind collagens, which indicates that the polymerized structure of CbsA is needed for collagen-binding ability. The C-terminal region, which is highly identical in S-layer proteins of L. crispatus, Lactobacillus acidophilus and Lactobacillus helveticus, was shown to anchor the protein to the bacterial cell wall. The C-terminal CbsA peptide specifically bound to bacterial teichoic acid and lipoteichoic acids. In conclusion, the N-terminal domain of the S-layer protein of L. crispatus is important for polymerization and adhesion to host tissues, whereas the C-terminal domain anchors the protein to bacterial cell-wall teichoic acids. Lactobacilli are fermentative organisms that effectively lower the surrounding pH. While this study was in progress, plasminogen-binding proteins enolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were identified in the extracellular proteome of L. crispatus ST1. In this work, the cell-wall association of enolase and GAPDH were shown to rely on pH-reversible binding to the cell-wall lipoteichoic acids. Enolase from L. crispatus was functionally compared with enolase from L. johnsonii as well as from pathogenic streptococci (Streptococcus pneumoniae, Streptococcus pyogenes) and Staphylococcus aureus. His6-enolases from commensal lactobacilli bound human plasminogen and enhanced its activation by human plasminogen activators similarly to, or even better than, the enolases from pathogens. Similarly, the His6-enolases from lactobacilli exhibited adhesive characteristics previously assigned to pathogens. The results call for more detailed analyses of the role of the host plasminogen system in bacterial pathogenesis and commensalism as well of the biological role and potential health risk of the extracellular proteome in lactobacilli.

Novel TBK1 truncating mutation in a familial amyotrophic lateral sclerosis patient of Chinese origin

Missense and frameshift mutations in TRAF family member-associated NF-kappa-B activator (TANK)-binding kinase 1 (TBK1) have been reported in European sporadic and familial amyotrophic lateral sclerosis (ALS) cohorts. To assess the role of TBK1 in ALS patient cohorts of wider ancestry, we have analyzed whole-exome sequence data from an Australian cohort of familial ALS (FALS) patients and controls. We identified a novel TBK1 deletion (c.1197delC) in a FALS patient of Chinese origin. This frameshift mutation (p.L399fs) likely results in a truncated protein that lacks functional domains required for adapter protein binding, as well as protein activation and structural integrity. No novel or reported TBK1 mutations were identified in FALS patients of European ancestry. This is the first report of a TBK1 mutation in an ALS patient of Asian origin and indicates that sequence variations in TBK1 are a rare cause of FALS in Australia. © 2015 Elsevier Inc.

Malaria rapid diagnostic test performance: Results of WHO product testing of malaria RDTs: Round 6 (2014-2015)

Overview This report, published in conjunction with a summary overview of results of rounds 1–6, is the sixth in a series of laboratory-based evaluations of rapid diagnostic tests (RDTs) for malaria. It provides a comparative measure of their performance in a standardized way to distinguish between well and poorly performing tests. It can be used by malaria control programmes and guide WHO procurement recommendations for these diagnostic tools. The evaluation reported here was a joint project of the WHO Global Malaria Programme, the Foundation for Innovative New Diagnostics (FIND) and the United States Centers for Disease Control and Prevention (CDC) within the WHO-FIND Malaria RDT Evaluation Programme. The project was financed by FIND through a grant from UNITAID.

Next generation sequencing identifies novel CACNA1A gene mutations in Episodic Ataxia type 2

Episodic Ataxia type 2 (EA2) is a rare autosomal dominantly inherited neurological disorder characterized by recurrent disabling imbalance, vertigo and episodes of ataxia lasting minutes to hours. EA2 is caused most often by loss of function mutations of the calcium channel gene CACNA1A. In addition to EA2, mutations in CACNA1A are responsible for two other allelic disorders: familial hemiplegic migraine type1 (FHM1) and spinocerebellar ataxia type 6 (SCA6). Herein, we have utilised Next Generation Sequencing (NGS) to screen the coding sequence, exon-intron boundaries and UTRs of five genes where mutation is known to produce symptoms related to EA2, including CACNA1A. We performed this screening in a group of 31 unrelated patients with EA2 symptoms. Both novel and known mutations were detected through NGS technology, and confirmed through Sanger sequencing. Genetic testing showed in total 15 mutation bearing patients (48%), of which 9 were novel mutations (6 missense and 3 small frameshift deletion mutations) and six known mutations (4 missense and 2 nonsense).These results demonstrate the efficiency of our NGS-panel for detecting known and novel mutations for EA2 in the CACNA1A gene, also identifying a novel missense mutation in ATP1A2 which is not a normal target for EA2 screening.

Pastoral care in times of high stakes testing and accountability

The unknown future is a challenge to educators in preparing young people for life post school. While history can be said to repeat itself, the reality is that each generation is faced with new challenges and threats. Therefore, the challenge for contemporary schooling is to prepare students to live in a fast paced, complex world where threats such as terrorism, cyberbullying and depleted resources are juggled with high stakes testing and curriculum accountability. This presentation draws on the notion of a future of supercomplexity while critically examining current pastoral care delivery in schools to develop a new model of practice in preparing students for an unknown future.

Functional Imagery Training to reduce snacking: Testing a novel motivational intervention based on Elaborated Intrusion theory

Functional Imagery Training (FIT) is a new theory-based, manualized intervention that trains positive goal imagery. Multisensory episodic imagery of proximal personal goals is elicited and practised, to sustain motivation and compete with less functional cravings. This study tested the impact of a single session of FIT plus a booster phone call on snacking. In a stepped-wedge design, 45 participants who wanted to lose weight or reduce snacking were randomly assigned to receive a session of FIT immediately or after a 2-week delay. High-sugar and high-fat snacks were recorded using timeline follow back for the previous 3 days, at baseline, 2 and 4 weeks. At 2 weeks, snacking was lower in the immediate group than in the delayed group, and the reduction after FIT was replicated in the delayed group between 2 and 4 weeks. Frequencies of motivational thoughts about snack reduction rose following FIT for both groups, and this change correlated with reductions in snacking and weight loss. By showing that FIT can support change in eating behaviours, these findings show its potential as a motivational intervention for weight management.

A distinct physiological role of MutY in mutation prevention in mycobacteria

Oxidative damage to DNA results in the occurrence of 7,8-dihydro-B-oxoguanine (8-oxoG) in the genome. In eubacteria, repair of such damage is initiated by two major base-excision repair enzymes, MutM and MutY. We generated a MutY-deficient strain of Mycobacterium smegmatis to investigate the role of this enzyme in DNA repair. The MutY deficiency in M. smegmatis did not result in either a noteworthy susceptibility to oxidative stress or an increase in the mutation rate. However, rifampicin resistant isolates of the MutY-deficient strain showed distinct mutations in the rifampicin-resistance-determining region of rpoB. Besides the expected C to A (or G to T) mutations, an increase in A to C (or T to G) mutations was also observed. Biochemical characterization of mycobacterial MutY (M. smegmatis and M. tuberculosis) revealed an expected excision of A opposite 8-oxoG in DNA. Additionally, excision of G and T opposite 8-oxoG was detected. MutY formed complexes with DNA containing 8-oxoG: A, 8-oxoG: G or 8-oxoG: T but not 8-oxoG : C pairs. Primer extension reactions in cell-free extracts of M. smegmatis suggested error-prone incorporation of nucleotides into the DNA. Based on these observations, we discuss the physiological role of MutY in specific mutation prevention in mycobacteria.

Mechanism of failure in a free-standing Pt-aluminide bond coat during tensile testing at room temperature

The room temperature (RT) tensile behaviour of a free-standing high activity Pt-aluminide bond coat has been evaluated by microtensile testing technique. The coating had a typical three-layer microstructure. The stress-strain plot for the free-standing coating was linear, indicating the coating to be brittle at RT. Different fracture features were observed across the coating layers, namely quasi-cleavage in the outer layer and inner interdiffusion zone, and cleavage in the intermediate layer. By employing interrupted tensile test and observing the cross-sectional microstructure of the tested specimens, it was determined that failure of the microtensile samples occurred by the initiation of a single crack in the intermediate layer of the coating and its subsequent inside-out propagation. Such a mechanism of failure has been explained in terms of the fracture features observed across the sample thickness. This mechanism of failure is consistent with fracture toughness values of the individual coating layers. (C) 2009 Elsevier B.V. All rights reserved.

Prostate cancer organoids: A potential new tool for testing drug sensitivity

Recent technical advances have enabled for the first time, reliable in vitro culture of prostate cancer samples as prostate cancer organoids. This breakthrough provides the significant possibility of high throughput drug screening covering the spectrum of prostate cancer phenotypes seen clinically. These advances will enable precision medicine to become a reality, allowing patient samples to be screened for effective therapeutics ex vivo, with tailoring of treatments specific to that individual. This will hopefully lead to enhanced clinical outcomes, avoid morbidity due to ineffective therapies and improve the quality of life in men with advanced prostate cancer.

Breath Testing by Fourier Transform Infrared Spectroscopy for Solvent Intoxication Diagnostics

Technical or contaminated ethanol products are sometimes ingested either accidentally or on purpose. Typical misused products are black-market liquor and automotive products, e.g., windshield washer fluids. In addition to less toxic solvents, these liquids may contain the deadly methanol. Symptoms of even lethal solvent poisoning are often non-specific at the early stage. The present series of studies was carried out to develop a method for solvent intoxication breath diagnostics to speed up the diagnosis procedure conventionally based on blood tests. Especially in the case of methanol ingestion, the analysis method should be sufficiently sensitive and accurate to determine the presence of even small amounts of methanol from the mixture of ethanol and other less-toxic components. In addition to the studies on the FT-IR method, the Dräger 7110 evidential breath analyzer was examined to determine its ability to reveal a coexisting toxic solvent. An industrial Fourier transform infrared analyzer was modified for breath testing. The sample cell fittings were widened and the cell size reduced in order to get an alveolar sample directly from a single exhalation. The performance and the feasibility of the Gasmet FT-IR analyzer were tested in clinical settings and in the laboratory. Actual human breath screening studies were carried out with healthy volunteers, inebriated homeless men, emergency room patients and methanol-intoxicated patients. A number of the breath analysis results were compared to blood test results in order to approximate the blood-breath relationship. In the laboratory experiments, the analytical performance of the Gasmet FT-IR analyzer and Dräger 7110 evidential breath analyzer was evaluated by means of artificial samples resembling exhaled breath. The investigations demonstrated that a successful breath ethanol analysis by Dräger 7110 evidential breath analyzer could exclude any significant methanol intoxication. In contrast, the device did not detect very high levels of acetone, 1-propanol and 2-propanol in simulated breath. The Dräger 7110 evidential breath ethanol analyzer was not equipped to recognize the interfering component. According to the studies the Gasmet FT-IR analyzer was adequately sensitive, selective and accurate for solvent intoxication diagnostics. In addition to diagnostics, the fast breath solvent analysis proved feasible for controlling the ethanol and methanol concentration during haemodialysis treatment. Because of the simplicity of the sampling and analysis procedure, non-laboratory personnel, such as police officers or social workers, could also operate the analyzer for screening purposes.

Experimental investigation on lateral impact response of concrete-filled double-skin tube columns using horizontal-impact-testing system

This paper presents an experimental investigation on the lateral impact performance of axially loaded concrete-filled double-skin tube (CFDST) columns. These columns have desirable structural and constructional properties and have been used as columns in building, legs of off shore platforms and as bridge piers. Since they could be vulnerable to impact from passing vessels or vehicles, it is necessary to understand their behaviour under lateral impact loads. With this in mind, an experimental method employing an innovative instrumented horizontal impact testing system (HITS) was developed to apply lateral impact loads whilst the column maintained a static axial pre-loading to examine the failure mechanism and key response parameters of the column. These included the time histories of impact force, reaction forces, global lateral deflection and permanent local buckling profile. Eight full scale columns were tested for key parameters including the axial load level and impact location. Based on the test data, the failure mode, peak impact force, impact duration, peak reaction forces, reaction force duration, column maximum and residual global deflections and column local buckling length, depth and width under varying conditions are analysed and discussed. It is evident that the innovative HITS can successfully test structural columns under the combination of axial pre-loading and impact loading. The findings on the lateral impact response of the CFDST columns can serve as a benchmark reference for their future analysis and design.

Testing and Modeling of MR Damper and Its Application to SDOF Systems Using Integral Backstepping Technique

Magnetorheological dampers are intrinsically nonlinear devices, which make the modeling and design of a suitable control algorithm an interesting and challenging task. To evaluate the potential of magnetorheological (MR) dampers in control applications and to take full advantages of its unique features, a mathematical model to accurately reproduce its dynamic behavior has to be developed and then a proper control strategy has to be taken that is implementable and can fully utilize their capabilities as a semi-active control device. The present paper focuses on both the aspects. First, the paper reports the testing of a magnetorheological damper with an universal testing machine, for a set of frequency, amplitude, and current. A modified Bouc-Wen model considering the amplitude and input current dependence of the damper parameters has been proposed. It has been shown that the damper response can be satisfactorily predicted with this model. Second, a backstepping based nonlinear current monitoring of magnetorheological dampers for semi-active control of structures under earthquakes has been developed. It provides a stable nonlinear magnetorheological damper current monitoring directly based on system feedback such that current change in magnetorheological damper is gradual. Unlike other MR damper control techniques available in literature, the main advantage of the proposed technique lies in its current input prediction directly based on system feedback and smooth update of input current. Furthermore, while developing the proposed semi-active algorithm, the dynamics of the supplied and commanded current to the damper has been considered. The efficiency of the proposed technique has been shown taking a base isolated three story building under a set of seismic excitation. Comparison with widely used clipped-optimal strategy has also been shown.

Molecular characterization of mitochondrial ataxias : with emphasis on MIRAS and IOSCA

Uusi hermoston rappeumasairaus MIRAS: Suomessa kantajia joka 125. väestöstä Tässä väitöskirjatyössä on kuvattu uusi peittyvästi periytyvä hermoston rappeumasairaus, MIRAS (mitochondrial recessive ataxia syndrome), ja sen geenitausta. Tauti osoittautui tutkimuksessamme Suomen yleisimmäksi perinnölliseksi ataksiasairaudeksi. Tutkimuksessa on tutkittu perinnöllisiä aivosairauksia, joissa yhtenä oireena on ataksia (kävelyn epävarmuus, tasapainovaikeus ja liikkeiden haparointi), sekä lukuisia muita aivojen toimintahäiriöstä johtuvia oireita. Seuloessamme suomalaisilta ataksiapotilailta MIRAS-geenivirhettä, 27 potilasta sai diagnoosin aikaisemmin tuntemattomalle, etenevälle ataksiasairaudelleen. Tutkimuksen tuloksena kyseisen geenivirheen DNA-diagnostiikka on otettu käyttöön suomalaisissa ja eurooppalaisissa laboratorioissa, ja toista sataa potilasta ympäri maailman on saanut diagnoosin. Suomen väestössä joka 125. kantaa MIRAS geenivirhettä, mutta taudin saa vain, jos perii geenivirheen molemmilta vanhemmiltaan. MIRAS on taudinkuvaltaan vaihteleva, mutta vaikea etenevä neurologinen sairaus. Useilla potilailla esiintyvät oireet ovat ataksia, puheen puuromaisuus (dysartria), ääreishermorappeuma (neuropatia), pakkoliikkeet, psykiatriset oireet sekä vaikea epilepsia. Erityisen tärkeää MIRAS-taudin tunnistaminen on siihen liittyvän epilepsian hoitopäätöksessä: valproaatti-lääkitys voi aiheuttaa MIRAS-potilaille vaikean maksavaurion. Väitöskirjatyön tuloksena selvisi, että kaikki suomalaiset, norjalaiset, belgialaiset, englantilaiset, australialaiset ja uusi-seelantilaiset MIRAS potilaat olivat kaukaista sukua samalle, tuhansia vuosia sitten eläneelle eurooppalaiselle esivanhemmalle. Ataksiasairauksien tautimekanismeja selvitimme tutkimalla MIRAS-ataksiaa ja sitä muistuttavaa IOSCA sairautta (infantile onset spinocerebellar ataxia), jonka aiheuttaa peittyvästi periytyvä geenivirhe Twinkle-geenissä. Tutkimuksessa löydettiin myös uusi, Twinkle-geenin geenivirheestä johtuva taudinkuva: vaikea-asteinen, varhaisella iällä alkava aivosairaus, jossa on lisäksi viitteitä maksasairaudesta. Löysimme potilaiden aivoista muutoksia mitokondrioiden eli solun voimalaitosten perimän määrässä. Nämä tulokset antavat arvokasta lisätietoa ataksiasairauksien taustalla olevista muutoksista, joiden ymmärtäminen on välttämätön edellytys hoitomahdollisuuksien tutkimiselle tulevaisuudessa.

Ventricular repolarization during cardiovascular autonomic function testing

The autonomic nervous system is an important modulator of ventricular repolarization and arrhythmia vulnerability. This study explored the effects of cardiovascular autonomic function tests on repolarization and its heterogeneity, with a special reference to congenital arrhythmogenic disorders typically associated with stress-induced fatal ventricular arrhythmias. The first part explored the effects of standardized autonomic tests on QT intervals in a 12-lead electrocardiogram and in multichannel magnetocardiography in 10 healthy adults. The second part studied the effects of deep breathing, Valsalva manouvre, mental stress, sustained handgrip and mild exercise on QT intervals in asymptomatic patients with LQT1 subtype of the hereditary long QT syndrome (n=9) and in patients with arrhythmogenic right ventricular dysplasia (ARVD, n=9). Even strong sympathetic activation had no effects on spatial QT interval dispersion in healthy subjects, but deep respiratory efforts and Valsalva influenced it in ways that were opposite in electrocardiographic and magnetocardiographic recordings. LQT1 patients showed blunted QT interval and sinus nodal responses to sympathetic challenge, as well as an exaggerated QT prolongation during the recovery phases. LQT1 patients showed a QT interval recovery overshoot in 2.4 ± 1.7 tests compared with 0.8 ± 0.7 in healthy controls (P = 0.02). Valsalva strain prolonged the T wave peak to T wave end interval only in the LQT1 patients, considered to reflect the arrhythmogenic substrate in this syndrome. ARVD patients showed signs of abnormal repolarization in the right ventricle, modulated by abrupt sympathetic activation. An electrocardiographic marker reflecting interventricular dispersion of repolarization was introduced. It showed that LQT1 patients exhibit a repolarization gradient from the left ventricle towards the right ventricle, significantly larger than in controls. In contrast, ARVD patients showed a repolarization gradient from the right ventricle towards the left. Valsalva strain amplified the repolarization gradient in LQT1 patients whereas it transiently reversed it in patients with ARVD. In conclusion, intrathoracic volume and pressure changes influence regional electrocardiographic and magnetocardiographic QT interval measurements differently. Especially recovery phases of standard cardiovascular autonomic functions tests and Valsalva manoeuvre reveal the abnormal repolarization in asymptomatic LQT1 patients. Both LQT1 and ARVD patients have abnormal interventricular repolarization gradients, modulated by abrupt sympathetic activation. Autonomic testing and in particular the Valsalva manoeuvre are potentially useful in unmasking abnormal repolarization in these syndromes.