Effectiveness-implementation hybrid type 2 study evaluating an intervention to support ‘information work’ in dementia care: an implementation study protocol

Introduction Patients with long-term conditions consistently report a lack of information around services and support available to them. This unmet need for information is significant among people with dementia and family carers. A quality improvement intervention is being carried out to tackle this issue as part of a co-creation initiative in the North East of England (UK). The intervention consists of the dissemination (via the local Community Mental Health Services for Older People) of a leaflet about services available to people with dementia and their family carers in the study site. This protocol is reported in accordance with the Standards for Reporting Implementation Studies. Methods and analysis This effectiveness–implementation hybrid type 2 study aims at understanding (1) the unfolding and outcomes of the implementation strategy, (2) the outcomes of the intervention (for people with dementia and family carers, staff implementing the intervention and local service providers) and (3) the contribution of co-creation to the design and implementation of the intervention and its outcomes. The prospective theory of change of the intervention articulated by local stakeholders is used as a reference framework against which to assess the implementation and outcomes of the intervention. Evaluation data will be collected through in-depth interviews with people with dementia and family carers receiving the intervention, staff implementing the intervention and managers from local service providers. Referral data from local service providers will be collected to triangulate the interview data. A focus group with key stakeholders will support the sense-making of findings. The realist configuration of mechanism–context–outcome, operationalised using an information behaviour model, will inform data analysis and interpretation. Ethics and dissemination Ethical and research governance approvals have been obtained from the West Midlands—South Birmingham Research Ethics Committee. The results of the study will be submitted for publication in peer-reviewed journals and disseminated through conferences

High-temperature phase transitions in dense germanium.

Through a series of high-pressure x-ray diffraction experiments combined with in situ laser heating, we explore the pressure-temperature phase diagram of germanium (Ge) at pressures up to 110 GPa and temperatures exceeding 3000 K. In the pressure range of 64-90 GPa, we observe orthorhombic Ge-IV transforming above 1500 K to a previously unobserved high-temperature phase, which we denote as Ge-VIII. This high-temperature phase is characterized by a tetragonal crystal structure, space group I4/mmm. Density functional theory simulations confirm that Ge-IV becomes unstable at high temperatures and that Ge-VIII is highly competitive and dynamically stable at these conditions. The existence of Ge-VIII has profound implications for the pressure-temperature phase diagram, with melting conditions increasing to much higher temperatures than previous extrapolations would imply

An intimate collaboration between peroxisomes and lipid bodies

Although peroxisomes oxidize lipids, the metabolism of lipid bodies and peroxisomes is thought to be largely uncoupled from one another. In this study, using oleic acid–cultured Saccharomyces cerevisiae as a model system, we provide evidence that lipid bodies and peroxisomes have a close physiological relationship. Peroxisomes adhere stably to lipid bodies, and they can even extend processes into lipid body cores. Biochemical experiments and proteomic analysis of the purified lipid bodies suggest that these processes are limited to enzymes of fatty acid β oxidation. Peroxisomes that are unable to oxidize fatty acids promote novel structures within lipid bodies (“gnarls”), which may be organized arrays of accumulated free fatty acids. However, gnarls are suppressed, and fatty acids are not accumulated in the absence of peroxisomal membranes. Our results suggest that the extensive physical contact between peroxisomes and lipid bodies promotes the coupling of lipolysis within lipid bodies with peroxisomal fatty acid oxidation

Evaluating the effects of an exercise program (Staying UpRight) for older adults in long-term care on rates of falls: study protocol for a randomised controlled trial

Background: Falls are two to four times more frequent amongst older adults living in long-term care (LTC) than community-dwelling older adults and have deleterious consequences. It is hypothesised that a progressive exercise program targeting balance and strength will reduce fall rates when compared to a seated exercise program and do so cost effectively. Methods/design: This is a single blind, parallel-group, randomised controlled trial with blinded assessment of outcome and intention-to-treat analysis. LTC residents (age ≥ 65 years) will be recruited from LTC facilities in New Zealand. Participants (n = 528 total, with a 1:1 allocation ratio) will be randomly assigned to either a novel exercise program (Staying UpRight), comprising strength and balance exercises designed specifically for LTC and acceptable to people with dementia (intervention group), or a seated exercise program (control group). The intervention and control group classes will be delivered for 1 h twice weekly over 1 year. The primary outcome is rate of falls (per 1000 person years) within the intervention period. Secondary outcomes will be risk of falling (the proportion of fallers per group), fall rate relative to activity exposure, hospitalisation for fall-related injury, change in gait variability, volume and patterns of ambulatory activity and change in physical performance assessed at baseline and after 6 and 12 months. Cost-effectiveness will be examined using intervention and health service costs. The trial commenced recruitment on 30 November 2018. Discussion: This study evaluates the efficacy and cost-effectiveness of a progressive strength and balance exercise program for aged care residents to reduce falls. The outcomes will aid development of evidenced-based exercise programmes for this vulnerable population. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12618001827224. Registered on 9 November 2018. Universal trial number U1111-1217-7148

Improving fairness in machine learning systems: What do industry practitioners need?

The potential for machine learning (ML) systems to amplify social inequities and unfairness is receiving increasing popular and academic attention. A surge of recent work has focused on the development of algorithmic tools to assess and mitigate such unfairness. If these tools are to have a positive impact on industry practice, however, it is crucial that their design be informed by an understanding of real-world needs. Through 35 semi-structured interviews and an anonymous survey of 267 ML practitioners, we conduct the first systematic investigation of commercial product teams' challenges and needs for support in developing fairer ML systems. We identify areas of alignment and disconnect between the challenges faced by industry practitioners and solutions proposed in the fair ML research literature. Based on these findings, we highlight directions for future ML and HCI research that will better address industry practitioners' needs.Comment: To appear in the 2019 ACM CHI Conference on Human Factors in Computing Systems (CHI 2019

Human ASPM participates in spindle organisation, spindle orientation and cytokinesis

Background Mutations in the Abnormal Spindle Microcephaly related gene (ASPM) are the commonest cause of autosomal recessive primary microcephaly (MCPH) a disorder characterised by a small brain and associated mental retardation. ASPM encodes a mitotic spindle pole associated protein. It is suggested that the MCPH phenotype arises from proliferation defects in neural progenitor cells (NPC). Results We show that ASPM is a microtubule minus end-associated protein that is recruited in a microtubule-dependent manner to the pericentriolar matrix (PCM) at the spindle poles during mitosis. ASPM siRNA reduces ASPM protein at the spindle poles in cultured U2OS cells and severely perturbs a number of aspects of mitosis, including the orientation of the mitotic spindle, the main determinant of developmental asymmetrical cell division. The majority of ASPM depleted mitotic cells fail to complete cytokinesis. In MCPH patient fibroblasts we show that a pathogenic ASPM splice site mutation results in the expression of a novel variant protein lacking a tripeptide motif, a minimal alteration that correlates with a dramatic decrease in ASPM spindle pole localisation. Moreover, expression of dominant-negative ASPM C-terminal fragments cause severe spindle assembly defects and cytokinesis failure in cultured cells. Conclusions These observations indicate that ASPM participates in spindle organisation, spindle positioning and cytokinesis in all dividing cells and that the extreme C-terminus of the protein is required for ASPM localisation and function. Our data supports the hypothesis that the MCPH phenotype caused by ASPM mutation is a consequence of mitotic aberrations during neurogenesis. We propose the effects of ASPM mutation are tolerated in somatic cells but have profound consequences for the symmetrical division of NPCs, due to the unusual morphology of these cells. This antagonises the early expansion of the progenitor pool that underpins cortical neurogenesis, causing the MCPH phenotype

Empowerment or Engagement? Digital Health Technologies for Mental Healthcare

We argue that while digital health technologies (e.g. artificial intelligence, smartphones, and virtual reality) present significant opportunities for improving the delivery of healthcare, key concepts that are used to evaluate and understand their impact can obscure significant ethical issues related to patient engagement and experience. Specifically, we focus on the concept of empowerment and ask whether it is adequate for addressing some significant ethical concerns that relate to digital health technologies for mental healthcare. We frame these concerns using five key ethical principles for AI ethics (i.e. autonomy, beneficence, non-maleficence, justice, and explicability), which have their roots in the bioethical literature, in order to critically evaluate the role that digital health technologies will have in the future of digital healthcare

Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system

Purpose A handheld device (the RETeval system, LKC Technologies) aims to increase the ease of electroretinogram (ERG) recording by using specially designed skin electrodes, rather than corneal electrodes. We explored effects of electrode position on response parameters recorded using this device. Methods Healthy adult twins were recruited from the TwinsUK cohort and underwent recording of light-adapted flicker ERGs (corresponding to international standard stimuli). In Group 1, skin electrodes were placed in a “comfortable” position, which was up to 20 mm below the lid margin. For subsequent participants (Group 2), the electrode was positioned 2 mm from the lid margin as recommended by the manufacturer. Amplitudes and peak times (averaged from both eyes) were compared between groups after age-matching and inclusion of only one twin per pair. Light-adapted flicker and flash ERGs were recorded for an additional 10 healthy subjects in two consecutive recording sessions: in the test eye, electrode position was varied from 2 to 10–20 mm below the lid margin between sessions; in the fellow (control) eye, the electrode was 2 mm below the lid margin throughout. Amplitudes and peak times (test eye normalised to control eye) were compared for the two sessions. Results Including one twin per pair, and age-matching yielded 28 individuals per group. Flicker ERG amplitudes were significantly lower for Group 1 than Group 2 participants (p = 0.0024). However, mean peak times did not differ between groups (p = 0.54). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly lower when positioned further from the lid margin (p  0.5). Conclusions Moving the skin electrodes further from the lid margin significantly reduces response amplitudes, highlighting the importance of consistent electrode positioning. However, this does not significantly affect peak times. Thus, it may be feasible to adopt a more comfortable position in participants who cannot tolerate the recommended position if analysis is restricted to peak time parameters

Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative

Objectives: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit\u27s Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders?. Methods/Design: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer\u27s disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson\u27s disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. Results: We found three components in the ZBI. The first was “overall burden” and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = −0.566, basic ADLs r = −0.43), (2) moderately related to cognition (MoCA r = −0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. Conclusions: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions

Metabolic syndrome in rural Australia:An opportunity for primary health care

Objective: To measure the impact of a 6-month home-based behaviour change intervention on reducing the risk of chronic disease as determined by metabolic syndrome status and cardiovascular risk score, and discuss implications for primary care in rural areas. Design: A two-arm randomised controlled trial of rural adults. Setting: The rural town of Albany in the Great Southern region of Western Australia. Participants: Participants (n = 401) aged 50-69 years who were classified with or at risk of metabolic syndrome and randomly assigned to intervention (n = 201) or waitlisted control (n = 200) group. Interventions: A 6-month intervention program incorporating goal setting, self-monitoring and feedback, with motivational interviewing was conducted. Main outcome measures: Change in metabolic syndrome status and cardiovascular risk. Results: Significant improvements in metabolic syndrome status and cardiovascular disease risk score (−0.82) were observed for the intervention group relative to control group from baseline to post-test. Conclusion: This home-based physical activity and nutrition intervention reduced participants' risk of experiencing a cardiovascular event in the next 5 years by 1%. Incorporating such prevention orientated approaches in primary care might assist in reducing the burden of long-term chronic diseases. However, for realistic application in this setting, hurdles such as current national health billing system and availability of resources will need to be considered