Exploring the Synthesis, Structure and Reactivity of a Series of Aluminium Amidinates

The work presented in this thesis relates to the synthesis of sterically encumbered aluminium amidinate complexes and investigating their propensity to catalyse hydroboration reactions or form aluminium-aluminium multiple bonds. The sterically encumbered 2,6-diphenylmethyl-4-methylphenyl substituent (referred to as Ar*) was employed to synthesise a range of symmetric and asymmetric amidine ligands which, upon complexation to aluminium reagents, yielded a series of aluminium hydride and alkyl amidinate complexes. These compounds were characterised spectroscopically and crystallographically, and any discrepancies between the solid- and solution-state properties have been accounted for. The propensity of these compounds to catalyse the hydroboration of phenylacetylene using 4,4,5,5-Tetramethyl-1,2,3-dioxaborolane (HBpin) was investigated. The aluminium hydride complexes were found to be active catalysts for this reaction and the alkyl compounds were pre-catalysts. Rates of reaction varied across this series of compounds which can be tentatively linked to the steric encumbrance of the flanking aryl substituents. Where deviations from this trend were observed, they could be rationalised by assessment of the solution-state stability of the complexes. Detailed experimental investigations were conducted to elucidate the mechanism of action. Variation in the observed mechanistic pathways was observed across this seemingly-similar family of compounds, with these pathways being different to previous literature reports of aluminium-catalysed hydroboration reactions. Finally, these compounds were explored for their viability as precursors to form aluminium-aluminium bonds. Aluminium amidinate and -diketiminate dihydrides were reacted with a known aluminium(I) reagent to obtain a series of amidinateAl-Al--diketiminate and asymmetric -diketiminateAl-Al--diketiminate dialumane complexes with varying steric encumbrance. Preliminary spectroscopic analyses are discussed, with ongoing investigations for complete characterisation and further reactivity

Phenotypic detection of AmpC β-lactamases, extended-spectrum- β-lactamases and metallo-β-lactamases in Enterobacteriaceae using a resazurin microtitre assay with inhibitor-based methods.

Dissemination of antibiotic resistance in Enterobacteriaceae mediated by AmpC, ESBL and MBL β-lactamases is clinically significant. A simple, relatively quick method for the detection of these resistance phenotypes would greatly improve chemotherapeutic recommendation. This technology would provide valuable input in our surveillance of resistance on a global stage, particularly if the methodology could be applicable to resource poor settings. A resazurin microtitre plate (RMP) assay incorporating cloxacillin, clavulanic acid, and EDTA for the rapid phenotypic identification of AmpC, Extended-spectrum-β-lactmase (ESBL), metallo-β-lactamase (MBL) and the co-existence of β-lactamases has been developed. A total of 47 molecularly characterised Enterobacteriaceae clinical isolates producing AmpCs, ESBLs, co-producers of ESBL and AmpC, MBLs, and co-producers of ESBL and MBL were phenotypically examined using the RMP assay. The ceftazidime (CAZ)-based and cefotaxime (CTX)-based RMP assay successfully detected all 16 AmpC, 14 ESBL, 9 MBL producers, 6 ESBL-AmpC co-producers, and 2 ESBL-MBL co-producers without false positive results. The CAZ-based assay was more reliable in detecting AmpC alone, while the CTX-based assay performed better in identifying co-producers of ESBL and AmpC. There was no difference in detection of ESBL and MBL producers. The findings of the present study suggest that use of the RMP assay with particular β-lactamase inhibitors explicitly detects three different β-lactamases, as well as co-existence of β-lactamases within 6 h after initial isolation of the pathogen. This assay is applicable to carry out in any laboratory, is cost-effective and easy to interpret. It could be implemented in screening patients, controlling infection and for surveillance purposes

Being prepared for emotionally demanding research

Research on topics such as child sexual abuse can be emotionally demanding for researchers in ways that surpass many other lines of work. Burrell et al. draw on their own experience to offer recommendations that may help increase researchers’ resilience to these challenges

Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation

In mammals, the ATM (ataxia-telangiectasia-mutated) and ATR (ATM and Rad3-related) protein kinases function as critical regulators of the cellular DNA damage response. The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2. In mammalian cells, evidence has been presented that Chk1 is devoted to the ATR signaling pathway and is modified by ATR in response to replication inhibition and UV-induced damage, whereas Chk2 functions primarily through ATM in response to ionizing radiation (IR), suggesting that Chk2 and Chk1 might have evolved to channel the DNA damage signal from ATM and ATR, respectively. We demonstrate here that the ATR-Chk1 and ATM-Chk2 pathways are not parallel branches of the DNA damage response pathway but instead show a high degree of cross-talk and connectivity. ATM does in fact signal to Chk1 in response to IR. Phosphorylation of Chk1 on Ser-317 in response to IR is ATM-dependent. We also show that functional NBS1 is required for phosphorylation of Chk1, indicating that NES1 might facilitate the access of Chk1 to ATM at the sites of DNA damage. Abrogation of Chk1 expression by RNA interference resulted in defects in IR-induced S and G2/M phase checkpoints; however, the overexpression of phosphorylation site mutant (S317A, S345A or S317A/S345A double mutant) Chk1 failed to interfere with these checkpoints. Surprisingly, the kinase-dead Chk1 (D130A) also failed to abrogate the S and G2 checkpoint through any obvious dominant negative effect toward endogenous Chk1. Therefore, further studies will be required to assess the contribution made by phosphorylation events to Chk1 regulation. Overall, the data presented in the study challenge the model in which Chk1 only functions downstream from ATR and indicate that ATM does signal to Chk1. In addition, this study also demonstrates that Chk1 is essential for IR-induced inhibition of DNA synthesis and the G2/M checkpoint

C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth—study protocol for a randomised controlled trial

Abstract Background Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach. Methods C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0–27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children’s Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat. Discussion To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies. Trial registration ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018

Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial

Background: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage. Methods: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349. Findings: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI –0·02 to 0·03]). Interpretation: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes. Funding: National Institute of Health Research Health Technology Assessment Programme

Crop Updates 2006 - Lupins and Pulses

This session covers sixty six papers from different authors: 2005 LUPIN AND PULSE INDUSTRY HIGHLIGHTS 1. Lupin Peter White, Department of Agriculture 2. Pulses Mark Seymour, Department of Agriculture 3. Monthly rainfall at experimental sites in 2005 4. Acknowledgements Amelia McLarty EDITOR 5. Contributors 6. Background Peter White, Department of Agriculture 2005 REGIONAL ROUNDUP 7. Northern agricultural region Wayne Parker, Department of Agriculture 8. Central agricultural region Ian Pritchard and Bob French, Department of Agriculture 9. Great southern and lakes Rodger Beermier, Department of Agriculture 10. South east region Mark Seymour, Department of Agriculture LUPIN AND PULSE PRODUCTION AGRONOMY AND GENETIC IMPROVEMENT 11. Lupin Peter White, Department of Agriculture 12. Narrow-leafed lupin breeding Bevan Buirchell, Department of Agriculture 13. Progress in the development of pearl lupin (Lupinus mutabilis) for Australian agriculture, Mark Sweetingham1,2, Jon Clements1, Geoff Thomas2, Roger Jones1, Sofia Sipsas1, John Quealy2, Leigh Smith1 and Gordon Francis1 1CLIMA, The University of Western Australia 2Department of Agriculture 14. Molecular genetic markers and lupin breeding, Huaan Yang, Jeffrey Boersma, Bevan Buirchell, Department of Agriculture 15. Construction of a genetic linkage map using MFLP, and identification of molecular markers linked to domestication genes in narrow-leafed lupin (Lupinus augustiflolius L) Jeffrey Boersma1,2, Margaret Pallotta3, Bevan Buirchell1, Chengdao Li1, Krishnapillai Sivasithamparam2 and Huaan Yang1 1Department of Agriculture, 2The University of Western Australia, 3Australian Centre for Plant Functional Genomics, South Australia 16. The first gene-based map of narrow-leafed lupin – location of domestication genes and conserved synteny with Medicago truncatula, M. Nelson1, H. Phan2, S. Ellwood2, P. Moolhuijzen3, M. Bellgard3, J. Hane2, A. Williams2, J. Fos‑Nyarko4, B. Wolko5, M. Książkiewicz5, M. Cakir4, M. Jones4, M. Scobie4, C. O’Lone1, S.J. Barker1, R. Oliver2, and W. Cowling1 1School of Plant Biology, The University of Western Australia, 2Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University, 3Centre for Bioinformatics and Biological Computing, Murdoch University, 4School of Biological Sciences and Biotechnology, SABC, Murdoch University,5Institute of Plant Genetics, Polish Academy of Sciences, Poznań, Poland 17. How does lupin optimum density change row spacing? Bob French and Laurie Maiolo, Department of Agriculture 18. Wide row spacing and seeding rate of lupins with conventional and precision seeding machines Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 19. Influence of row spacing and plant density on lupin competition with annual ryegrass, Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 20. Effect of timing and speed of inter-row cultivation on lupins, Martin Harries, Jo Walker and Steve Cosh, Department of Agriculture 21. The interaction of atrazine herbicide rate and row spacing on lupin seedling survival, Martin Harries and Jo Walker Department of Agriculture 22. The banding of herbicides on lupin row crops, Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 23. Large plot testing of herbicide tolerance of new lupin lines, Wayne Parker, Department of Agriculture 24. Effect of seed source and simazine rate of seedling emergence and growth, Peter White and Greg Shea, Department of Agriculture 25. The effect of lupin row spacing and seeding rate on a following wheat crop, Martin Harries, Jo Walker and Dirranie Kirby, Department of Agriculture 26. Response of crop lupin species to row spacing, Leigh Smith1, Kedar Adhikari1, Jon Clements2 and Patrizia Guantini3, 1Department of Agriculture, 2CLIMA, The University of Western Australia, 3University of Florence, Italy 27. Response of Lupinus mutabilis to lime application and over watering, Peter White, Leigh Smith and Mark Sweetingham, Department of Agriculture 28. Impact of anthracnose on yield of Andromeda lupins, Geoff Thomas, Kedar Adhikari and Katie Bell, Department of Agriculture 29. Survey of lupin root health (in major production areas), Geoff Thomas, Ken Adcock, Katie Bell, Ciara Beard and Anne Smith, Department of Agriculture 30. Development of a generic forecasting and decision support system for diseases in the Western Australian wheatbelt, Tim Maling1, Art Diggle1,2, Debbie Thackray1, Kadambot Siddique1 and Roger Jones1,2 1CLIMA, The University of Western Australia, 2Department of Agriculture 31.Tanjil mutants highly tolerant to metribuzin, Ping Si1, Mark Sweetingham1,2, Bevan Buirchell1,2 and Huaan Yang l,2 1CLIMA, The University of Western Australia, 2Department of Agriculture 32. Precipitation pH vs. yield and functional properties of lupin protein isolate, Vijay Jayasena1, Hui Jun Chih1 and Ken Dods2 1Curtin University of Technology, 2Chemistry Centre 33. Lupin protein isolation with the use of salts, Vijay Jayasena1, Florence Kartawinata1,Ranil Coorey1 and Ken Dods2 1Curtin University of Technology, 2Chemistry Centre 34. Field pea, Mark Seymour, Department of Agriculture 35. Breeding highlights Kerry Regan1,2, Tanveer Khan1,2, Stuart Morgan1 and Phillip Chambers1 1Department of Agriculture, 2CLIMA, The University of Western Australia 36. Variety evaluation, Kerry Regan1,2, Tanveer Khan1,2, Jenny Garlinge1 and Rod Hunter1 1Department of Agriculture, 2CLIMA, The University of Western Australia 37. Days to flowering of field pea varieties throughout WA Mark Seymour1, Ian Pritchard1, Rodger Beermier1, Pam Burgess1 and Dr Eric Armstrong2 Department of Agriculture, 2NSW Department of Primary Industries, Wagga Wagga 38. Semi-leafless field peas yield more, with less ryegrass seed set, in narrow rows, Glen Riethmuller, Department of Agriculture 39. Swathing, stripping and other innovative ways to harvest field peas, Mark Seymour, Ian Pritchard, Rodger Beermier and Pam Burgess, Department of Agriculture 40. Pulse demonstrations, Ian Pritchard, Wayne Parker, Greg Shea, Department of Agriculture 41. Field pea extension – focus on field peas 2005, Ian Pritchard, Department of Agriculture 42. Field pea blackspot disease in 2005: Prediction versus reality, Moin Salam, Jean Galloway, Pip Payne, Bill MacLeod and Art Diggle, Department of Agriculture 43. Pea seed-borne mosaic virus in pulses: Screening for seed quality defects and virus resistance, Rohan Prince, Brenda Coutts and Roger Jones, Department of Agriculture, and CLIMA, The University of Western Australia 44. Yield losses from sowing field peas infected with pea seed-borne mosaic virus, Rohan Prince, Brenda Coutts and Roger Jones, Department of Agriculture, and CLIMA, The University of Western Australia 45. Desi chickpea, Wayne Parker, Department of Agriculture 46. Breeding highlights, Tanveer Khan 1,2, Pooran Gaur3, Kadambot Siddique2, Heather Clarke2, Stuart Morgan1and Alan Harris1, 1Department of Agriculture2CLIMA, The University of Western Australia, 3International Crop Research Institute for Semi Arid Tropics (ICRISAT), India 47. National chickpea improvement program, Kerry Regan1, Ted Knights2 and Kristy Hobson3,1Department of Agriculture, 2Agriculture New South Wales 3Department of Primary Industries, Victoria 48. Chickpea breeding lines in CVT exhibit excellent ascochyta blight resistance, Tanveer Khan1,2, Alan Harris1, Stuart Morgan1 and Kerry Regan1,2, 1Department of Agriculture, 2CLIMA, The University of Western Australia 49. Variety evaluation, Kerry Regan1,2, Tanveer Khan1,2, Jenny Garlinge2 and Rod Hunter2, 1CLIMA, The University of Western Australia 2Department of Agriculture 50. Desi chickpeas for the wheatbelt, Wayne Parker and Ian Pritchard, Department of Agriculture 51. Large scale demonstration of new chickpea varieties, Wayne Parker, MurrayBlyth, Steve Cosh, Dirranie Kirby and Chris Matthews, Department of Agriculture 52. Ascochyta management with new chickpeas, Martin Harries, Bill MacLeod, Murray Blyth and Jo Walker, Department of Agriculture 53. Management of ascochyta blight in improved chickpea varieties, Bill MacLeod1, Colin Hanbury2, Pip Payne1, Martin Harries1, Murray Blyth1, Tanveer Khan1,2, Kadambot Siddique2, 1Department of Agriculture, 2CLIMA, The University of Western Australia 54. Botrytis grey mould of chickpea, Bill MacLeod, Department of Agriculture 55. Kabuli chickpea, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 56. New ascochyta blight resistant, high quality kabuli chickpea varieties, Kerry Regan1,2, Kadambot Siddique2, Tim Pope2 and Mike Baker1, 1Department of Agriculture, 2CLIMA, The University of Western Australia 57. Crop production and disease management of Almaz and Nafice, Kerry Regan and Bill MacLeod, Department of Agriculture, and CLIMA, The University of Western Australia 58. Faba bean,Mark Seymour, Department of Agriculture 59. Germplasm evaluation – faba bean, Mark Seymour1, Tim Pope2, Peter White1, Martin Harries1, Murray Blyth1, Rodger Beermier1, Pam Burgess1 and Leanne Young1,1Department of Agriculture, 2CLIMA, The University of Western Australia 60. Factors affecting seed coat colour of faba bean during storage, Syed Muhammad Nasar-Abbas1, Julie Plummer1, Kadambot Siddique2, Peter White 3, D. Harris4 and Ken Dods4.1The University of Western Australia, 2CLIMA, The University of Western Australia, 3Department of Agriculture, 4Chemistry Centre 61. Lentil,Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 62. Variety and germplasm evaluation, Kerry Regan1,2, Tim Pope2, Leanne Young1, Phill Chambers1, Alan Harris1, Wayne Parker1 and Michael Materne3, 1Department of Agriculture 2CLIMA, The University of Western Australia, 3Department of Primary Industries, Victoria Pulse species 63. Land suitability for production of different crop species in Western Australia, Peter White, Dennis van Gool, and Mike Baker, Department of Agriculture 64. Genomic synteny in legumes: Application to crop breeding, Huyen Phan1, Simon Ellwood1, J. Hane1, Angela Williams1, R. Ford2, S. Thomas3 and Richard Oliver1,1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University 2BioMarka, School of Agriculture and Food Systems, ILFR, University of Melbourne 3NSW Department of Primary Industries 65. ALOSCA – Development of a dry flow legume seed inoculant, Rory Coffey and Chris Poole, ALOSCA Technologies Pty Ltd 66. Genetic dissection of resistance to fungal necrotrophs in Medicago truncatula, Simon Ellwood1, Theo Pfaff1, Judith Lichtenzveig12, Lars Kamphuis1, Nola D\u27Souza1, Angela Williams1, Emma Groves1, Karam Singh2 and Richard Oliver1 1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University, 2CSIRO Plant Industry APPENDIX I: LIST OF COMMON ACRONYM

Eyewitness Testimony in Autism Spectrum Disorder: A Review

Autism spectrum disorder (ASD) is estimated to affect around 1% of the population, and is characterised by impairments in social interaction, communication, and behavioural flexibility. A number of risk factors indicate that individuals with ASD may become victims or witnesses of crimes. In addition to their social and communication deficits, people with ASD also have very specific memory problems, which impacts on their abilities to recall eyewitnessed events. We begin this review with an overview of the memory difficulties that are experienced by individuals with ASD, before discussing the studies that have specifically examined eyewitness testimony in this group and the implications for investigative practice. Finally, we outline related areas that would be particularly fruitful for future research to explore

Abstracts from the NIHR INVOLVE Conference 2017

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