Showing papers by "Andrew J. Martin published in 2021"

Impact of Coronavirus Disease 2019 Public Health Measures on Detections of Influenza and Respiratory Syncytial Virus in Children During the 2020 Australian Winter.

Abstract: Public health measures targeting coronavirus disease 2019 have potential to impact transmission of other respiratory viruses. We found 98.0% and 99.4% reductions in respiratory syncytial virus and influenza detections, respectively, in Western Australian children through winter 2020 despite schools reopening. Border closures have likely been important in limiting external introductions.

Outbreak of anorexia nervosa admissions during the COVID-19 pandemic.

Abstract: The COVID-19 pandemic has had broad social implications for children around the world. While the initial government response has focused on public health strategies to contain the spread of the virus and the creation of sufficient capacity within hospitals to manage patients with acute medical complications, it was recognised that the social, economic and mental health consequences of COVID-19 would follow. In Western Australia (WA), we have had relatively few COVID-19 cases in the general population and even fewer in children. Similar to paediatric hospitals internationally,1 our emergency department presentations and overall hospital admissions have fallen significantly in 2020 (figure 1). However, since the commencement of the COVID-19 pandemic in Australia, we have observed a 104% increase (95% CI +56% to +166%, p<0.001) in children with anorexia nervosa (AN) requiring …

Examining the interseasonal resurgence of respiratory syncytial virus in Western Australia.

Abstract: BACKGROUND: Following a relative absence in winter 2020, a large resurgence of respiratory syncytial virus (RSV) detections occurred during the 2020/2021 summer in Western Australia. This seasonal shift was linked to SARS-CoV-2 public health measures. We examine the epidemiology and RSV testing of respiratory-coded admissions, and compare clinical phenotype of RSV-positive admissions between 2019 and 2020. METHOD: At a single tertiary paediatric centre, International Classification of Diseases, 10th edition Australian Modification-coded respiratory admissions longer than 12 hours were combined with laboratory data from 1 January 2019 to 31 December 2020. Data were grouped into bronchiolitis, other acute lower respiratory infection (OALRI) and wheeze, to assess RSV testing practices. For RSV-positive admissions, demographics and clinical features were compared between 2019 and 2020. RESULTS: RSV-positive admissions peaked in early summer 2020, following an absent winter season. Testing was higher in 2020: bronchiolitis, 94.8% vs 89.2% (p=0.01); OALRI, 88.6% vs 82.6% (p=0.02); and wheeze, 62.8% vs 25.5% (p<0.001). The 2020 peak month, December, contributed almost 75% of RSV-positive admissions, 2.5 times the 2019 peak. The median age in 2020 was twice that observed in 2019 (16.4 vs 8.1 months, p<0.001). The proportion of RSV-positive OALRI admissions was greater in 2020 (32.6% vs 24.9%, p=0.01). There were no clinically meaningful differences in length of stay or disease severity. INTERPRETATION: The 2020 RSV season was in summer, with a larger than expected peak. There was an increase in RSV-positive non-bronchiolitis admissions, consistent with infection in older RSV-naive children. This resurgence raises concern for regions experiencing longer and more stringent SARS-CoV-2 public health measures.

Integrated Guidance for Enhancing the Care of Familial Hypercholesterolaemia in Australia

Abstract: Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics. To further address the unmet need, we provide an updated guidance, presented as a series of systematically collated recommendations, on the care of patients and families with FH. These recommendations have been informed by an exponential growth in published works and new evidence over the last 5 years and are compatible with a contemporary global call to action on FH. Recommendations are given on the detection, diagnosis, assessment and management of FH in adults and children. Recommendations are also made on genetic testing and risk notification of biological relatives who should undergo cascade testing for FH. Guidance on management is based on the concepts of risk re-stratification, adherence to heart healthy lifestyles, treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-cholesterol lowering therapies, including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis. Broad recommendations are also provided for the organisation and development of health care services. Recommendations on best practice need to be underpinned by good clinical judgment and shared decision making with patients and families. Models of care for FH need to be adapted to local and regional health care needs and available resources. A comprehensive and realistic implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits all Australian families with or at risk of FH.

Understanding Teacher Wellbeing Through Job Demands-Resources Theory

Abstract: Job demands-resources (JD-R) theory has emerged as one of the most influential conceptual frameworks for interpreting and explaining factors affecting employees’ wellbeing in the workplace. The present chapter provides a broad overview of JD-R theory, and discusses how the theory can be harnessed to further understand the factors influencing teachers’ wellbeing. The chapter also reviews prior research employing JD-R theory in teaching populations, and explores the job demands (e.g., workload, disciplinary issues, time pressure) and job resources (e.g. perceived autonomy support, opportunities for professional learning, and relationships with colleagues) that influence teacher engagement, burnout, and organisational outcomes. Theoretical extensions of the model, such as the inclusion of personal resources (e.g. adaptability, cognitive and behavioural coping, self-efficacy), are further considered to extend knowledge of how teacher wellbeing can be promoted at both an individual and broader organisational level. Finally, the chapter considers the practical implications of how JD-R theory can guide interventions, comprising whole-school efforts, as well as approaches that support individual teachers to maximise their wellbeing.

Adaptability and Social Support: Examining Links With Psychological Wellbeing Among UK Students and Non-students.

Abstract: The purpose of this multi-study article was to investigate the roles of adaptability and social support in predicting a variety of psychological outcomes. Data were collected from Year 12 college students (N = 73; Study 1), university students (N = 102; Study 2), and non-studying members of the general public (N = 141; Study 3). Findings showed that, beyond variance attributable to social support, adaptability made a significant independent contribution to psychological wellbeing (life satisfaction, psychological wellbeing, flourishing, and general affect) and psychological distress across all studies. Beyond the effects of adaptability, social support was found to make a significant independent contribution to most wellbeing outcomes (but not psychological distress in university students). In a multi-group analysis comparing predictors of psychological wellbeing in university students and non-studying adults, where the same outcome measures were used (Study 4; N = 243), it was found that adaptability played a stronger role (relative to social support) for university students, whereas social support played a stronger role for non-studying adults. Finally, (contrary to expectations) there was no evidence of an interaction between adaptability and social support predicting psychological outcomes-adaptability and social support operated as independent main effects. These findings demonstrate the importance of adaptability and social support in uniquely predicting psychological wellbeing in different sample groups. It is argued here that these two factors, should be given greater consideration in discussions of psychological wellbeing, and are relevant to psychological wellbeing at different major developmental life stages.

Adaptability and High School Students' Online Learning During COVID-19: A Job Demands-Resources Perspective.

Abstract: The present study investigated the role of adaptability in helping high school students navigate their online learning during a period of COVID-19 that entailed fully or partially remote online learning. Drawing on Job Demands-Resources theory and data from a sample of 1,548 Australian high school students in nine schools, we examined the role of adaptability in predicting students' online learning self-efficacy in mathematics and their end of year mathematics achievement. It was found that beyond the effects of online learning demands, online and parental learning support, and background attributes, adaptability was significantly associated with higher levels of online learning self-efficacy and with gains in later achievement; online learning self-efficacy was also significantly associated with gains in achievement-and significantly mediated the relationship between adaptability and achievement. These findings confirm the role of adaptability as an important personal resource that can help students in their online learning, including through periods of remote instruction, such as during COVID-19.

Load reduction instruction in science and students' science engagement and science achievement

Abstract: Among a sample of 2,071 Australian high school students nested within 188 science classrooms, the present study explored the role of science teachers’ “load reduction instruction” (LRI; instruction that seeks to reduce cognitive load by appropriately balancing explicit instruction with guided autonomy) in student- and classroom-level science engagement and the role of engagement in student- and classroom-level science achievement. Using doubly latent multilevel structural equation modeling, results showed that, at the student- and classroom-level, student reports of their teacher’s LRI was significantly and positively associated with self-reported engagement, and engagement was significantly and positively associated with achievement. Thus, (a) LRI was associated with greater individual student engagement, that in turn was associated with greater individual student achievement in science, and (b) beyond student-level effects, LRI was associated with greater classroom engagement that in turn was associated with greater classroom achievement. We also found that the association between LRI and achievement was mediated by engagement. Implications for educational practice in science are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

The “ins and outs” of student engagement in mathematics: shifts in engagement factors among high and low achievers

Abstract: Student engagement in mathematics in the early secondary years can be fragile. Engagement in learning fluctuates in response to students’ mathematics experiences and is underpinned by numerous adaptive and maladaptive factors. Thirty-seven 11–12 year old students (grades 6–7) responded twice to a questionnaire to measure shifts in their engagement and motivation over a 1-year period as they transitioned from primary to secondary school. When plotted on spider graphs, the results of specific adaptive and maladaptive factors visually demonstrate “in and out” movements as students’ engagement levels shifted from time 1 to time 2. Subsequent semistructured interviews complemented questionnaire data by eliciting student beliefs about their achievement, feelings and behaviours towards mathematics. Interview data shed light on the reasons for individual student shifts in motivation and engagement during the transition. Together, data reveal four unique engagement/achievement characteristics. Significantly, students who were more alike in terms of their engagement reported similar factor patterns regardless of their achievement level. Findings draw attention to the importance of addressing mathematics engagement for students of all achievement levels.

The role of mobile technology in promoting social inclusion among adults with intellectual disabilities.

Abstract: BACKGROUND Mobile technology has the potential to assist adults with intellectual disabilities to initiate and maintain social connections in important areas of their lives, such as family, friends and work/volunteering. METHOD The present study investigated how specific aspects of mobile device/app use are associated with the social inclusion of people with intellectual disabilities. The study also examined what background attributes were associated with particular patterns of mobile device/app use and social inclusion. RESULTS The findings revealed that the use of mobile technology among adults with intellectual disabilities was positively associated with their social inclusion with family, friends and work/volunteering. There were also some key background attributes associated with participants' use of mobile technology and the extent to which mobile technology assisted their social inclusion. CONCLUSIONS Implications for practice and policy are discussed.

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901).

Abstract: Objectives To determine the activity and safety of lutetium-177 (177 Lu)-prostate-specific membrane antigen (PSMA)-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. Participants and methods ENZA-p (ANZUP 1901) is an open-label, randomized, two-arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177 Lu-PSMA-617 7.5 GBq on Days 15 and 57. Two additional 177 Lu-PSMA-617 doses are allowed, informed by Day-92 Gallium-68 (68 Ga)-PSMA positron emission tomography (PET; up to four doses in total). The primary endpoint is prostate-specific antigen (PSA) progression-free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health-related quality of life, adverse events and cost-effectiveness. Key eligibility criteria include: biochemical and/or clinical progression; 68 Ga-PSMA PET-avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high-risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68 Ga-PSMA PET at baseline, Days 15 and 92, and at progression, and 18 F-fluorine deoxyglucose (18 F-FDG) PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga-PSMA and 18 F-FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two-sided type-1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. Results and conclusion The combination of 177 Lu-PSMA-617 and enzalutamide may be synergistic. ENZA-p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.

Teacher assistants working with students with disability: the role of adaptability in enhancing their workplace wellbeing

Abstract: There is much research into teachers’ workplace wellbeing, but very little research investigating teacher assistants’ wellbeing in the workplace – especially those who work in classrooms where stud...

Rapid resistance of FGFR-driven gastric cancers to regorafenib and targeted FGFR inhibitors can be overcome by parallel inhibition of MEK

Abstract: Amplification or overexpression of the FGFR family of receptor tyrosine kinases occurs in a significant proportion of gastric cancers Regorafenib is a multikinase inhibitor of angiogenic and oncogenic kinases, including FGFR, which showed activity in the randomized phase II INTEGRATE clinical trial in advanced gastric cancer There are currently no biomarkers that predict response to this agent, and whether regorafenib is preferentially active in FGFR-driven cancers is unknown Through screening 25 gastric cancer cell lines, we identified five cell lines that were exquisitely sensitive to regorafenib, four of which harbored amplification or overexpression of FGFR family members These four cell lines were also sensitive to the FGFR-specific inhibitors, BGJ398, erdafitinib, and TAS-120 Regorafenib inhibited FGFR-driven MAPK signaling in these cell lines, and knockdown studies confirmed their dependence on specific FGFRs for proliferation In the INTEGRATE trial cohort, amplification or overexpression of FGFRs 1-4 was detected in 8%-19% of cases, however, this was not associated with improved progression-free survival and no objective responses were observed in these cases Further preclinical analyses revealed FGFR-driven gastric cancer cell lines rapidly reactivate MAPK/ERK signaling in response to FGFR inhibition, which may underlie the limited clinical response to regorafenib Importantly, combination treatment with an FGFR and MEK inhibitor delayed MAPK/ERK reactivation and synergistically inhibited proliferation of FGFR-driven gastric cancer cell lines These findings suggest that upfront combinatorial inhibition of FGFR and MEK may represent a more effective treatment strategy for FGFR-driven gastric cancers

Challenge and threat appraisals in high school science: investigating the roles of psychological and physiological factors

Abstract: While completing a science test and science survey, 155 high school students wore a biometric wristband (measuring electrodermal activity; EDA) and self-reported their science self-efficacy and sci...

Decision to reject screening for familial hypercholesterolaemia is flawed.

Abstract: The UK National Screening Committee (NSC) in February 2020 put thousands of families at risk of premature myocardial infarction by rejecting screening of children for familial hypercholesterolaemia (FH) to prevent ischaemic heart disease (IHD) FH is a silent killer of young adults There about 260 000 FH-positive individuals in the UK with only about 7% so far identified About half will have a myocardial infarction before age 50 years without treatment Prevention works if started early in life and is simple—lowering serum cholesterol, with statins, which abolishes the excess IHD risk caused by the high cholesterol1 Child-parent screening involves a heel prick blood test during routine immunisation at 1 year of age and once a child is identified the parents are tested; one will be affected since FH is inherited as an autosomal dominant and then other family members undergo cascade testing2 Such child-parent cascade screening and treatment would prevent about 4000 myocardial infarctions in the UK each year under age 50 years, about half of them fatal Why would this not be introduced as a national screening programme? The NSC came up with five reasons, all in our view, mistaken The first mistake was a failure to consider FH as a familial problem The NSC considered only the child and failed to recognise that preventing the premature death of a parent is a benefit, of course to the parent, and to the child and family The second mistake was a failure to recognise that an FH mutation is not the disorder, it is part of the …

Neu-horizons: neuroprotection and therapeutic use of riluzole for the prevention of oxaliplatin-induced neuropathy-a randomised controlled trial.

Abstract: Peripheral neuropathy is a commonly reported adverse effect of oxaliplatin treatment, representing a significant limitation which may require discontinuation of effective therapy The present study investigated the neuroprotective potential of riluzole in patients undergoing oxaliplatin treatment in a randomised-controlled trial comparing riluzole and placebo-control Fifty-two patients (17 females, 581 ± 127 years) receiving oxaliplatin treatment were randomised into either a treatment (50 mg riluzole) or lactose placebo group The primary outcome measure was the total neuropathy score-reduced (TNSr) Secondary outcome measures include nerve excitability measures, 9-hole pegboard and FACT-GOG NTX questionnaire Patients were assessed at baseline, pre-cycle 10 or 12, 4-week and 12-week post-treatment Both the treatment and placebo groups developed objective and patient reported evidence of neurotoxicity over the course of oxaliplatin treatment, although there were no significant differences across any parameters between the two groups However, across follow-up assessments, the treatment group experienced greater neuropathy, represented by a higher TNSr score at 4-week post-chemotherapy of 83 ± 27 compared with 46 ± 36 (p = 0032) which was sustained at 12-week post-treatment (p = 0089) Similarly, patients in the treatment group reported worse symptoms with a FACT-GOG NTX score of 374 ± 102 compared with 433 ± 74 (p = 002) in the placebo group at 4-week post-treatment This study is the first to provide an objective clinical investigation of riluzole in oxaliplatin-induced peripheral neuropathy employing both functional and neurophysiological measures Although the recruitment target was not reached, the results do not show any benefit of riluzole in minimising neuropathy and may suggest that riluzole worsens neuropathy associated with oxaliplatin treatment

Assessing the impact of the 13 valent pneumococcal vaccine on childhood empyema in Australia

Abstract: Background Empyema is a serious complication of pneumonia frequently caused by Streptococcus pneumoniae (SP). We assessed the impact of the 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyema after inclusion in the Australian National Immunisation Program. Methods For bacterial pneumonia and empyema hospitalisations, we ascertained incidence rates (IRs) using the National Hospital Morbidity Database International Statistical Classification of Disease discharge codes and relevant population denominators, and calculated incidence rate ratios (IRR) comparing the 13vPCV period (June 2012–May 2017) with the 7vPCV period (June 2007–May 2011). Blood and pleural fluid (PF) cultures and PF PCR of 401 children with empyema from 11 Australian hospitals during the 13vPCV period were compared with our previous study in the 7vPCV period. Findings Across 7vPCV and 13vPCV periods, IRs per million children (95% CIs) were 1605 (1588 to 1621) and 1272 (1259 to 1285) for bacterial pneumonia, and 14.23 (12.67 to 15.79) and 17.89 (16.37 to 19.42) for empyema hospitalisations. IRRs were 0.79 (0.78 to 0.80) for bacterial pneumonia and 1.25 (1.09 to 1.44) for empyema. Of 161 empyema cases with SP serotypes, 147 (91.3%) were vaccine types. ST3 accounted for 76.4% of identified serotypes in the 13vPCV period, more than double than the 7vPCV period (p Interpretation 13vPCV resulted in a significant reduction in all-cause hospitalisations for bacterial pneumonia but empyema hospitalisations significantly increased, with emergence of pneumococcal ST3 as the dominant serotype in empyema. Trial registration number Australian and New Zealand Clinical Trial Registry ACTRN 12614000354684.

Zincbindpredict-Prediction of Zinc Binding Sites in Proteins.

Abstract: Background: Zinc binding proteins make up a significant proportion of the proteomes of most organisms and, within those proteins, zinc performs roles in catalysis and structure stabilisation. Identifying the ability to bind zinc in a novel protein can offer insights into its functions and the mechanism by which it carries out those functions. Computational means of doing so are faster than spectroscopic means, allowing for searching at much greater speeds and scales, and thereby guiding complimentary experimental approaches. Typically, computational models of zinc binding predict zinc binding for individual residues rather than as a single binding site, and typically do not distinguish between different classes of binding site—missing crucial properties indicative of zinc binding. Methods: Previously, we created ZincBindDB, a continuously updated database of known zinc binding sites, categorised by family (the set of liganding residues). Here, we use this dataset to create ZincBindPredict, a set of machine learning methods to predict the most common zinc binding site families for both structure and sequence. Results: The models all achieve an MCC ≥ 0.88, recall ≥ 0.93 and precision ≥ 0.91 for the structural models (mean MCC = 0.97), while the sequence models have MCC ≥ 0.64, recall ≥ 0.80 and precision ≥ 0.83 (mean MCC = 0.87), with the models for binding sites containing four liganding residues performing much better than this. Conclusions: The predictors outperform competing zinc binding site predictors and are available online via a web interface and a GraphQL API.

Common mechanisms explain nitrogen-dependent growth of Arctic shrubs over three decades despite heterogeneous trends and declines in soil nitrogen availability

Abstract: Heterogeneity has been observed in the responses of Arctic shrubs to climate variability over recent decades, which may reflect landscape-scale variability in belowground resources. At a northern fringe of tall shrub expansion (Yuribei, Yamal Peninsula, Russia), we sought to determine the mechanisms relating nitrogen (N) limitation to shrub growth over decadal time. We analysed the ratio of 15 N to 14 N isotopes in wood rings of 10 Salix lanata individuals (399 measurements) to reconstruct annual point-based bioavailable N between 1980 and 2013. We applied a model-fitting/model-selection approach with a suite of competing ecological models to assess the most-likely mechanisms that explain each shrub's individual time-series. Shrub δ15 N time-series indicated declining (seven shrubs), increasing (two shrubs) and no trend (one shrub) in N availability. The most appropriate model for all shrubs included N-dependent growth of linear rather than saturating form. Inclusion of plant-soil feedbacks better explained ring width and δ15 N for eight of 10 individuals. Although N trajectories were individualistic, common mechanisms of varying strength confirmed the N-dependency of shrub growth. The linear mechanism may reflect intense scavenging of scarce N; the importance of plant-soil feedbacks suggests that shrubs subvert the microbial bottleneck by actively controlling their environment.

Motivation and engagement among Indigenous (Aboriginal Australian) and non-Indigenous students

Abstract: Among a sample of 472 Indigenous high school students, juxtaposed with 15,884 non-Indigenous students from the same 54 schools, we investigated variation in motivation and engagement from school to...

Intraoperative renal hypoxia and risk of cardiac surgery-associated acute kidney injury.

Abstract: BACKGROUND Acute kidney injury (AKI) is common after cardiac surgery requiring cardiopulmonary bypass. Renal hypoxia may precede clinically detectable AKI. We compared the efficacy of two indices of renal hypoxia, (i) intraoperative urinary oxygen tension (UPO2 ) and (ii) the change in plasma erythropoietin (pEPO) during surgery, in predicting AKI. We also investigated whether the performance of these prognostic markers varies with preoperative patient characteristics. METHODS In 82 patients undergoing on-pump cardiac surgery, blood samples were taken upon induction of anesthesia and upon entry into the intensive care unit. UPO2 was continuously measured throughout surgery. RESULTS Thirty-two (39%) patients developed postoperative AKI. pEPO increased during surgery, but this increase did not predict AKI, regardless of risk of postoperative mortality assessed by EuroSCORE-II. For patients categorized at higher risk by EuroSCORE-II >1.98 (median score for the cohort), UPO2 ≤10 mmHg at any time during surgery predicted a 4.04-fold excess risk of AKI (p = .04). However, UPO2 did not significantly predict AKI in lower-risk patients. UPO2 significantly predicted AKI in patients who were older, had previous myocardial infarction, diabetes, lower preoperative serum creatinine, or shorter bypass times. pEPO and UPO2 were only weakly correlated. CONCLUSIONS Intraoperative change in pEPO does not predict AKI. However, UPO2 shows promise, particularly in patients with higher risk of operative mortality. The disparity between these two markers of renal hypoxia may indicate that UPO2 reflects medullary oxygenation whereas pEPO reflects cortical oxygenation.

The role of teacher feedback–feedforward and personal best goal setting in students’ mathematics achievement: a goal setting theory perspective

Abstract: Teacher feedback in mathematics is a potential strategy for redressing declining international trends in high school mathematics achievement. Effective feedback comprises corrective informa...