Fifteen Years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and Observations from 2,359 Older Adults Spanning the Spectrum from Cognitive Normality to Alzheimer's Disease.

BACKGROUND: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer's disease dementia (AD)) as an 'Inception cohort' who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an 'Enrichment cohort' (as of 10 April 2019). OBJECTIVE: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. METHODS: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. RESULTS: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aß-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. CONCLUSION: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

Comparative study of a novel application of automated HR HPV assay and stability in a previously untested Preservative media.

BACKGROUND: The suitability and stability of cervical cells in Novaprep media (NHQ) for certain HPV assays is unknown. METHODS: We evaluated the accuracy of an automated HPV assay (Abbott RealTime HR HPV) for cervical cells prepared in NHQ and NHQ with a pre-treatment to mimic a worst case clinical use, compared to the assay manufacturers media; repeatability and reproducibility of HPV results and the stability of detectable HPV in NHQ over time compared to CE marked liquid based cytology preservatives. Cell lines were used to simulate patient samples. RESULTS: Cells stored in NHQ produced accurate, repeatable and reproducible results. Stability in NHQ was comparable to the best performing LBC, with at least 7 months' stability at 18-25°C, 2-8°C, -20°C and -80°C; and at least 3 months' stability at 40°C. Similar results were obtained for pre-treated NHQ except only 3.5 months' stability at 18-25°C. Cell line samples in all media and concentrations tested were detected appropriately by the assay. CONCLUSIONS: Based on this first stage validation analytical study, cervical cells stored in NHQ are suitable for the Realtime HPV assay. There should be no reservations for inclusion of NHQ in any further validation and clinical performance evaluation of this assay.

Hello Harlie: Enabling Speech Monitoring Through Chat-Bot Conversations.

People with neurological conditions such as Parkinson's disease and dementia are known to have difficulties in language and communication. This paper presents initial testing of an artificial conversational agent, called Harlie. Harlie runs on a smartphone and is able to converse with the user on a variety of topics. A description of the application and a sample dialog are provided to illustrate the various roles chat-bots can play in the management of neurological conditions. Harlie can be used for measuring voice and communication outcomes during the daily life of the user, and for gaining information about challenges encountered. Moreover, it is anticipated that she may also have an educational and support role.

Balancing Self-Tracking and Surveillance: Legal, Ethical and Technological Issues in Using Smartphones to Monitor Communication in People with Health Conditions.

Smartphones are being used to track the health of individuals in their own environments. For example, a smartphone app could be used to monitor the impact and progression of Parkinson's disease, as well as indicate whether treatments may need to be adjusted, based on an analysis of voice and discourse. The app uses smartphone audio sensors to detect when conversations are taking place and activates an app to record the conversation. But what happens if a background conversation is also collected by the recording? The participants of the background conversation are unaware of and have not consented to the recording. Unauthorised recording could also raise legal issues under surveillance devices legislation and has ethical implications. It is a complex task to balance the potential benefits of self-tracking of health conditions to consumers and the health system, with the legalities and ethical issues related to privacy. The health-related monitoring industry is moving so rapidly that current legal and ethical processes and protocols may fail to balance these concerns. This article explores Australian legal and ethical perspectives on how to achieve the potential benefits of these technological approaches while preserving privacy.

Adaptive Multi-Rate Compression Effects on Vowel Analysis.

Signal processing on digitally sampled vowel sounds for the detection of pathological voices has been firmly established. This work examines compression artifacts on vowel speech samples that have been compressed using the adaptive multi-rate codec at various bit-rates. Whereas previous work has used the sensitivity of machine learning algorithm to test for accuracy, this work examines the changes in the extracted speech features themselves and thus report new findings on the usefulness of a particular feature. We believe this work will have potential impact for future research on remote monitoring as the identification and exclusion of an ill-defined speech feature that has been hitherto used, will ultimately increase the robustness of the system.

Use of Smartphones to Estimate Carbohydrates in Foods for Diabetes Management.

Over 380 million adults worldwide are currently living with diabetes and the number has been projected to reach 590 million by 2035. Uncontrolled diabetes often lead to complications, disability, and early death. In the management of diabetes, dietary intervention to control carbohydrate intake is essential to help manage daily blood glucose level within a recommended range. The intervention traditionally relies on a self-report to estimate carbohydrate intake through a paper based diary. The traditional approach is known to be inaccurate, inconvenient, and resource intensive. Additionally, patients often require a long term of learning or training to achieve a certain level of accuracy and reliability. To address these issues, we propose a design of a smartphone application that automatically estimates carbohydrate intake from food images. The application uses imaging processing techniques to classify food type, estimate food volume, and accordingly calculate the amount of carbohydrates. To examine the proof of concept, a small fruit database was created to train a classification algorithm implemented in the application. Consequently, a set of fruit photos (n=6) from a real smartphone were applied to evaluate the accuracy of the carbohydrate estimation. This study demonstrates the potential to use smartphones to improve dietary intervention, although further studies are needed to improve the accuracy, and extend the capability of the smartphone application to analyse broader food contents.

Chat-Bots for People with Parkinson's Disease: Science Fiction or Reality?

People with Parkinson's disease are known to have difficulties in language and communication. This paper proposes the use of an artificial conversational agent, commonly known as a chat-bot that runs on a smart-phone device and performs two-way conversation with the user. In this paper, initial work on a Parkinson's disease themed chat-bot that interacts with the user relative to their symptoms is presented. Potential dialogues are provided to illustrate the various roles chat-bots can play in the management of Parkinson's disease. The chat-bot can be used for measuring voice and communication outcomes during the daily life of the user, and for gaining information about challenges encountered. Moreover, it is anticipated that it may also have an educational and support role. The chat-bot is now ready for usability testing with a clinical population.

STroke imAging pRevention and treatment (START): A longitudinal stroke cohort study: Clinical trials protocol.

RATIONALE: Stroke and poststroke depression are common and have a profound and ongoing impact on an individual's quality of life. However, reliable biological correlates of poststroke depression and functional outcome have not been well established in humans. AIMS: Our aim is to identify biological factors, molecular and imaging, associated with poststroke depression and recovery that may be used to guide more targeted interventions. DESIGN: In a longitudinal cohort study of 200 stroke survivors, the START-STroke imAging pRevention and Treatment cohort, we will examine the relationship between gene expression, regulator proteins, depression, and functional outcome. Stroke survivors will be investigated at baseline, 24 h, three-days, three-months, and 12 months poststroke for blood-based biological associates and at days 3-7, three-months, and 12 months for depression and functional outcomes. A sub-group (n = 100), the PrePARE: Prediction and Prevention to Achieve optimal Recovery Endpoints after stroke cohort, will also be investigated for functional and structural changes in putative depression-related brain networks and for additional cognition and activity participation outcomes. Stroke severity, diet, and lifestyle factors that may influence depression will be monitored. The impact of depression on stroke outcomes and participation in previous life activities will be quantified. STUDY OUTCOMES: Clinical significance lies in the identification of biological factors associated with functional outcome to guide prevention and inform personalized and targeted treatments. Evidence of associations between depression, gene expression and regulator proteins, functional and structural brain changes, lifestyle and functional outcome will provide new insights for mechanism-based models of poststroke depression.

Design of a multi-site multi-state clinical trial of home monitoring of chronic disease in the community in Australia.

BACKGROUND: Telehealth services based on at-home monitoring of vital signs and the administration of clinical questionnaires are being increasingly used to manage chronic disease in the community, but few statistically robust studies are available in Australia to evaluate a wide range of health and socio-economic outcomes. The objectives of this study are to use robust statistical methods to research the impact of at home telemonitoring on health care outcomes, acceptability of telemonitoring to patients, carers and clinicians and to identify workplace cultural factors and capacity for organisational change management that will impact on large scale national deployment of telehealth services. Additionally, to develop advanced modelling and data analytics tools to risk stratify patients on a daily basis to automatically identify exacerbations of their chronic conditions. METHODS/DESIGN: A clinical trial is proposed at five locations in five states and territories along the Eastern Seaboard of Australia. Each site will have 25 Test patients and 50 case matched control patients. All participants will be selected based on clinical criteria of at least two hospitalisations in the previous year or four or more admissions over the last five years for a range of one or more chronic conditions. Control patients are matched according to age, sex, major diagnosis and their Socio-Economic Indexes for Areas (SEIFA). The Trial Design is an Intervention control study based on the Before-After-Control-Impact (BACI) design. DISCUSSION: Our preliminary data indicates that most outcome variables before and after the intervention are not stationary, and accordingly we model this behaviour using linear mixed-effects (lme) models which can flexibly model within-group correlation often present in longitudinal data with repeated measures. We expect reduced incidence of unscheduled hospitalisation as well as improvement in the management of chronically ill patients, leading to better and more cost effective care. Advanced data analytics together with clinical decision support will allow telehealth to be deployed in very large numbers nationally without placing an excessive workload on the monitoring facility or the patient's own clinicians. TRIAL REGISTRATION: Registered with Australian New Zealand Clinical Trial Registry on 1st April 2013. Trial ID: ACTRN12613000635763.

Measuring the lifespace of people with Parkinson's disease using smartphones: proof of principle.

BACKGROUND: Lifespace is a multidimensional construct that describes the geographic area in which a person lives and conducts their activities, and reflects mobility, health, and well-being. Traditionally, it has been measured by asking older people to self-report the length and frequency of trips taken and assistance required. Global Positioning System (GPS) sensors on smartphones have been used to measure Lifespace of older people, but not with people with Parkinson's disease (PD). OBJECTIVE: The objective of this study was to investigate whether GPS data collected via smartphones could be used to indicate the Lifespace of people with PD. METHODS: The dataset was supplied via the Michael J Fox Foundation Data Challenge and included 9 people with PD and 7 approximately matched controls. Participants carried smartphones with GPS sensors over two months. Data analysis compared the PD group and the control group. The impact of symptom severity on Lifespace was also investigated. RESULTS: Visualization methods for comparing Lifespace were developed including scatterplots and heatmaps. Lifespace metrics for comparison included average daily distance, percentage of time spent at home, and number of trips into the community. There were no significant differences between the PD and the control groups on Lifespace metrics. Visual representations of Lifespace were organized based on the self-reported severity of symptoms, suggesting a trend of decreasing Lifespace with increasing PD symptoms. CONCLUSIONS: Lifespace measured by GPS-enabled smartphones may be a useful concept to measure the progression of PD and the impact of various therapies and rehabilitation programs. Directions for future use of GPS-based Lifespace are provided.

Rates of diagnostic transition and cognitive change at 18-month follow-up among 1,112 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL).

BACKGROUND: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimer's disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not. METHODS: Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging. RESULTS: The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinson's disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%. CONCLUSION: There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.

A technological evaluation of the Microsoft Kinect for automated behavioural mapping at bed rest.

Behavioural mapping (BM) is a long established method of structured observational study used to understand where patients are and what they are doing within a hospital setting. BM is prominent in stroke rehabilitation research, where that research indicates patients spend most of their time at bed rest. We evaluate the technical feasibility of using the Microsoft Kinect to automate patient physical activity classification at bed rest.

A method for the semantic enrichment of clinical trial data.

Clinical trial data have historically been implemented using relational databases. While this has expedited the dissemination of data among partners, it has hindered on the ability to swiftly query the data by relying on monolithic tables. This paper outlines a project that investigates the semantic enrichment of a large-scale longitudinal clinical trial, the AIBL study, by reusing entities from existing ontologies. The implication of the semantic enrichment of the AIBL study is that it is possible to query the data more effectively and efficiently. We are now able to implement our model and focus on an end-to-end data capture and analysis pipeline to query and visualise clinical trial data. The main contribution of this paper is a discussion of the methodology to semantically enrich clinical trial data using entities from existing ontologies.

Using Australian medicines terminology (AMT) and SNOMED CT-AU to better support clinical research.

A large scale, long term clinical study faced significant quality issues with its medications use data which had been collected from participants using paper forms and manually entered into a data capture system. A method was developed that automatically mapped 72.2% of the unique medication names collected for the study to the AMT and SNOMED CT-AU using Ontoserver, a terminology server for clinical ontologies. These initial results are promising and, with further improvements to the algorithms and evaluation, are expected to greatly improve the analysis of medication data gathered from the study.

On selecting a clinical trial management system for large scale, multi-centre, multi-modal clinical research study.

Clinical research studies offer many challenges for their supporting information systems. AIBL assembled 1112 participants who volunteered crucial information for a comprehensive study on neurodegenerative diseases. This paper discusses the shortcomings of the clinical trial management system chosen to record the results of the study. A set of guidelines was devised and a critique of five systems ensued. OpenClinica was selected as the most appropriate option. The main contribution of this paper is: (i) proposing a set of guidelines to determine the appropriateness of Clinical Trial Management Systems (CTMS) solution; (ii) providing a brief critique of existing commercial and open-sourced CTMS; and (iii) alluding to some data migration issues and providing cues on how to address them. We conclude that open-source CTMS are viable alternatives to the more expensive commercial systems to conduct, record and manage clinical studies.

A web-based normative data tool for assessing cognitive performance in healthy older Australians.

A decline in cognition greater than expected with ageing and accompanied by subjective cognitive concerns or functional changes may be indicative of a dementing disorder. The capacity to correctly identify cognitive decline relies on comparisons with normative data from a suitably matched healthy reference group with relatively homogeneous demographic features. Formal assessment of cognition is usually performed by specialist neuropsychologists trained in administration and interpretation of psychometric tests. With a scarcity of normative data from large cohorts of older adults, Australian neuropsychologists commonly use representative data from small international studies. Data from 727 healthy older Australians participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing have been used to create a normative dataset. A web-based calculator was developed to simplify the time-consuming process of comparing cognitive performance scores with these representative data.

Current practices in the management of adductor spasmodic dysphonia.

INTRODUCTION: Adductor spasmodic dysphonia (ADSD) is a focal dystonia treated most commonly by chemodenervation of the thyroarytenoid (TA) muscles with botulinum toxin. Currently, there are no consensus guidelines regarding this treatment and the management of ADSD. The objective of this study was to assess current practice patterns among physicians who treat ADSD. METHODS: A cross-sectional survey study was conducted regarding treatment choices and specific technical aspects of injection technique and botulinum toxin use. The study population consisted of laryngologists from the Canadian Society of Otolaryngology-Head and Neck Surgery and laryngologists obtained from the American Laryngological Association member database and the American Academy of Otolaryngology-Head and Neck Surgery Neurolaryngology Study Group. RESULTS: An overall response rate of 13% was achieved, with a high absolute number of physicians who manage ADSD responding (n = 37). Most respondents treat ADSD by injecting botulinum toxin type A (Botox) through the cricothyroid membrane submucosally at a mode starting dose of 2.5 units per TA muscle using electromyographic guidance with or without fibre-optic laryngoscopy every 3 to 4 months, with the frequency of reinjection being based on patient symptomatology. There is much variability with regard to starting injection dose, alternate treatments for ADSD, unilateral versus bilateral injections, and guidance technique. Most physicians (36 of 37) share one vial among more than one patient, and some (7 of 37) freeze a reconstituted vial that has remaining toxin for reuse at a later time. CONCLUSIONS: There is considerable variability in treatment practices for the management of ADSD. Further study is warranted to define an optimal therapeutic paradigm.

Alloantibodies against low-frequency human platelet antigens do not account for a significant proportion of cases of fetomaternal alloimmune thrombocytopenia: evidence from 1054 cases.

BACKGROUND: Maternal alloantibodies against the five common human platelet antigen (HPA) systems (HPA-1 to -3, -5, and -15) are found in only 20% of cases referred for fetal and neonatal thrombocytopenia (FMAIT) investigations. The question asked was whether mismatches for the remaining 11 low-frequency HPAs (HPA-4 and -6bw to -17bw) might in part explain the remaining 80% of cases. STUDY DESIGN AND METHODS: A total of 1054 paternal DNA samples from referred FMAIT cases (among which 223 cases where antibodies against a common HPA were found) were genotyped for 11 low-frequency HPAs as well as a recently discovered polymorphism (ITGA2B-C2320T). The initial genotyping was carried out by TaqMan and potential heterozygotes were confirmed by DNA sequencing. Clinical and serologic data were collected for each case with a heterozygote father. RESULTS: In total, eight heterozygous fathers were identified: four for HPA-6w, one each for HPA-10w and -11w, and two for HPA-12w. Maternal antibodies against the corresponding antigen were identified in four of the eight cases. In two of these cases, antibodies against HPA-1a and HPA-1b were also found. CONCLUSION: It was concluded that the minor alleles of HPA-4 and -6bw to -17bw are exceptionally rare in the Caucasian population and therefore do not explain the large number of FMAIT referrals which test negative for the common HPA antibodies.

Real-time PCR assays for high-throughput human platelet antigen typing.

Most human platelet alloantigen (HPA) systems comprise biallelic single nucleotide polymorphisms in genes encoding major membrane glycoproteins. Genotyping for these systems is required in the investigation of patients with suspected HPA antibodies and for the provision of compatible blood products from HPA-typed donor panel populations.