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Communications in space are rapidly increasing in both capacity and extension. A satellite network in space calls for efficient and lightweight optical transmitters, suitable to communicate over distances going from the low-Earth-orbit to interplanetary links and beyond. To this aims, here we study the use of novel resources as an array of nanoptical coupler from guided sources and modulators to free space modes, that is phased with a suitable correction systems as well as efficient coding with error corrections capable of bearing large values of losses. We develop a method for designing such an array, which achieve a main lobe divergence of 1 µrad. We also discuss the lower and upper limits of the beam steering technique as a function of the array and emitter size, respectively. The optimization of grating couples (GCs) resulted an apodized structure with approximately 0.7 coupling efficiency and 70-µm beam waist. We also demonstrate the feasibility of phase correction and polarization modulation of the output mode by means of metalenses. The resulting link budget in terms of received photons on the Earth sets exceptional conditions for the digital optical communication system, for which a power efficient modulation scheme such as pulse position modulation (PPM) is considered. Here, we assess the PPM performance and we propose suitable channel coding schemes, essential to reduce the high bit error rate obtained in few-photon regime at the receiver.

Abstract Background Most people with dementia live in the community, not in residential care. Therefore, quality informal care for them is critical for managing behavioural and psychological symptoms of dementia (BPSD). Music therapy has been shown to reduce BPSD. However, no randomised controlled trial has examined the effects of music interventions delivered by caregivers in home settings. The HOME-based caregiver-delivered music intervention for people living with dementia (HOMESIDE) trial aims to evaluate the effectiveness of a 12-week music intervention in addition to standard care for BPSD. This article describes the statistical analysis plan. Methods and analysis HOMESIDE is a large, pragmatic international three-arm parallel-group randomised controlled trial. Dyads (persons with dementia and caregiver) in Australia, Germany, the UK, Poland and Norway were randomised to receive music and standard care, reading and standard care or standard care alone. The primary outcome is BPSD (proxy) of the person living with dementia, measured using the Neuropsychiatric Inventory-Questionnaire (NPI-Q) at 90 and 180 days post-randomisation. Longitudinal analysis will compare NPI-Q severity between music and standard care versus standard care alone. Secondary outcomes include quality of life and depression (both person with dementia and caregiver), cognition (person with dementia only), distress, resilience, competence and caregiver-patient relationship (caregiver only). Treatment effects will be obtained at 90 and 180 days post-randomisation, where applicable. Safety outcomes (adverse events, hospitalisations, deaths) will be summarised. Discussion This statistical analysis plan provides a detailed methodology for the analysis of HOMESIDE and will improve the validity of the study and reduce the potential for bias. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12618001799246. Registered on November 05, 2018. ClinicalTrials.gov NCT03907748. Registered on April 09, 2019.

Summary: Background: Music interventions provided by qualified therapists within residential aged care are effective at attenuating behavioural and psychological symptoms (BPSD) of people with dementia (PwD). The impact of music interventions on dementia symptom management when provided by family caregivers is unclear. Methods: We implemented a community-based, large, pragmatic, international, superiority, single-masked randomised controlled trial to evaluate if caregiver-delivered music was superior to usual care alone (UC) on reducing BPSD of PwD measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q). The study included an active control (reading). People with dementia (NPI-Q score ≥6) and their caregiver (dyads) from one of five countries were randomly allocated to caregiver-delivered music, reading, or UC with a 1:1:1 allocation stratified by site. Caregivers received three online protocolised music or reading training sessions delivered by therapists and were recommended to provide five 30-min reading or music activities per week (minimum twice weekly) over 90-days. The NPI-Q severity assessment of PwD was completed online by masked assessors at baseline, 90- (primary) and 180-days post-randomisation and analysed on an intention-to-treat basis using a likelihood-based longitudinal data analysis model. ACTRN12618001799246; ClinicalTrials.gov NCT03907748. Findings: Between 27th November 2019 and 7th July 2022, we randomised 432 eligible of 805 screened dyads (music n = 143, reading n = 144, UC n = 145). There was no statistical or clinically important difference in the change from baseline BPSD between caregiver-delivered music (−0.15, 95% CI −1.41 to 1.10, p = 0.81) or reading (−1.12, 95% CI −2.38 to 0.14, p = 0.082) and UC alone at 90-days. No related adverse events occurred. Interpretation: Our findings suggested that music interventions and reading interventions delivered by trained caregivers in community contexts do not decrease enduring BPSD symptoms. Funding: Our funding was provided by National Health and Medical Research Council, Australia; The Research Council of Norway; Federal Ministry of Education and Research, Germany; National Centre for Research and Development, Poland; Alzheimer’s Society, UK, as part of the Joint Programme for Neurodegenerative Diseases consortia scheme.

Summary: Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development. Here, we describe the cardiac pathologies that developed in a mouse model of hypereosinophilic syndrome. These IL-5 transgenic mice exhibited decreased left ventricular function at a young age which worsened with age. Mechanistically, we demonstrated infiltration of activated eosinophils into the heart tissue that led to an inflammatory environment. Gene expression signatures showed tissue damage as well as repair and remodeling processes. Cardiomyocytes from IL-5Tg mice exhibited significantly reduced contractility relative to wild type (WT) controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca2+ reuptake in cardiomyocytes contributes to cardiac dysfunction at the whole organ level in hypereosinophilic mice.

Introduction Digital health interventions are cost-effective and easily accessible, but there is currently a lack of effective online options for dementia prevention especially for people at risk due to mild cognitive impairment (MCI) or subjective cognitive decline (SCD).Methods and analysis MyCOACH (COnnected Advice for Cognitive Health) is a tailored online dementia risk reduction programme for adults aged ≥65 living with MCI or SCD. The MyCOACH trial aims to evaluate the programme’s effectiveness in reducing dementia risk compared with an active control over a 64-week period (N=326). Eligible participants are randomly allocated to one of two intervention arms for 12 weeks: (1) the MyCOACH intervention programme or (2) email bulletins with general healthy ageing information (active control). The MyCOACH intervention programme provides participants with information about memory impairments and dementia, memory strategies and different lifestyle factors associated with brain ageing as well as practical support including goal setting, motivational interviewing, brain training, dietary and exercise consultations, and a 26-week post-intervention booster session. Follow-up assessments are conducted for all participants at 13, 39 and 65 weeks from baseline, with the primary outcome being exposure to dementia risk factors measured using the Australian National University-Alzheimer’s Disease Risk Index. Secondary measures include cognitive function, quality of life, functional impairment, motivation to change behaviour, self-efficacy, morale and dementia literacy.Ethics and dissemination Ethical approval was obtained from the University of New South Wales Human Research Ethics Committee (HC210012, 19 February 2021). The results of the study will be disseminated in peer-reviewed journals and research conferences.Trial registration number ACTRN12621000977875.

We describe an innovative case study focusing on a social robot able to help healthcare professionals compute criticality scores for patients hosted in a Geriatric Sub-Intensive Care Unit. The aim is to establish the feasibility of a scenario in which the robot modulates the frequency of its visits to the room of bedridden patients, based on the criticality scores it has computed.

Background: Nutrition claims on food labels are used to attract attention to products. Inaccurate claims on ready-to-eat (RTE) snack food products may mislead consumers into consuming a higher volume of a seemingly ‘healthy’ product. Objectives: A study was undertaken to determine the following surrounding the packaging of RTE snack food products: (i) compliance of health and or nutrient claims; (ii) average nutrient content per snack category; (iii) accuracy of the total energy content; (iv) eligibility to make claims once the R429 legislation is implemented. Outcome measures: Nutrient content per 100 g and serving size was analysed. Claims related to nutrient content were audited. Design: An analysis was undertaken of the labels of 93 South African-produced RTE snack food products from 10 categories, displaying health and or nutrition claims. Results: Ninety-one products displayed nutrient content claims. Twenty-three (25.3%) nutrient content claims were non-compliant with the R146 legislation. Twenty-one (22.6%) displayed negative claims, three (14.3%) were ineligible. Eighteen products (19.4%) displayed endorsement claims, four (4.4%) were eligible. Sixty-four products (68.8%) displayed a higher total energy content when applying the conversion factors to the displayed macronutrient values. Only 22 (23.7%) products would be eligible to make health and/or nutrition claims once the R429 legislation is promulgated. Conclusion: A higher proportion of eligible claims were found. More than 70% of food manufacturers will need to make changes to the nutrient content or labels once the R429 legislation is implemented. A two-pronged approach of manufacturer compliance and consumer education may improve food choices and reduce the incidence of obesity and NCDs.

Introduction Exercise and physical activity have been shown to improve cognition for people living with mild cognitive impairment (MCI). There is strong evidence for the benefits of aerobic exercise and medium evidence for participating in regular strength training for people with MCI. However, people living with MCI fall two times as often as those without cognitive impairment and the evidence is currently unknown as to whether balance training for people with MCI is beneficial, as has been demonstrated for older people without cognitive impairment. The aim of this study is to determine whether a balance-focused multimodal exercise intervention improves balance and reduces falls for people with MCI, compared with a control group receiving usual care.Methods and analysis This single blind randomised controlled trial (Balance on the Brain) will be offered to 396 people with MCI living in the community. The multimodal exercise intervention consists of two balance programmes and a walking programme to be delivered by physiotherapists over a 6-month intervention period. All participants will be followed up over 12 months (for the intervention group, this involves 6-month intervention and 6-month maintenance). The primary outcomes are (1) balance performance and (2) rate of falls. Physical performance, levels of physical activity and sedentary behaviour, quality of life and cognition are secondary outcomes. A health economic analysis will be undertaken to evaluate the cost-effectiveness of the intervention compared with usual care.Ethics and dissemination Ethics approval has been received from the South Metropolitan Health Service Human Research Ethics Committee (HREC), Curtin University HREC and the Western Australia Department of Health HREC; and approval has been received to obtain data for health costings from Services Australia. The results will be disseminated through peer-review publications, conference presentations and online platforms.Trial registration number ACTRN12620001037998; Australian New Zealand Clinical Trials Registry (ANZCTR).

Abstract Introduction Superior cognitive performance in older adults may reflect underlying resistance to age‐associated neurodegeneration. While elevated amyloid β (Aβ) deposition (Aβ+) has been associated with increased cortical atrophy, it remains unknown whether “SuperAgers” may be protected from Aβ‐associated neurodegeneration. Methods Neuropsychologically defined SuperAgers (n = 172) and cognitively normal for age (n = 172) older adults from the Australian Imaging, Biomarkers and Lifestyle study were case matched. Rates of cortical atrophy over 8 years were examined by SuperAger classification and Aβ status. Results Of the case‐matched SuperAgers and cognitively normal for age older adults, 40.7% and 40.1%, respectively, were Aβ+. Rates of age‐ and Aβ‐associated atrophy did not differ between the groups on any measure. Aβ− individuals displayed the slowest rates of atrophy. Discussion Maintenance of superior memory in late life does not reflect resistance to age‐ or Aβ‐associated atrophy. However, those individuals who reached old age without cognitive impairment nor elevated Aβ deposition (i.e. Aβ−) displayed reduced rates of cortical atrophy.

BackgroundOlder patients account for a significant proportion of patients undergoing colorectal cancer surgery and are vulnerable to a number of preoperative risk factors that are not often present in younger patients. Further, three preoperative risk factors that are more prevalent in older adults include frailty, sarcopenia, and malnutrition. Although each of these has been studied in isolation, there is little information on the interplay between them in older surgical patients. A particular area of increasing interest is the use of urine metabolomics for the objective evaluation of dietary profiles and malnutrition. ObjectiveHerein, we describe the design, cohort, and standard operating procedures of a planned prospective study of older surgical patients undergoing colorectal cancer resection across multiple institutions in the United Kingdom. The objectives are to determine the association between clinical outcomes and frailty, nutritional status, and sarcopenia. MethodsThe procedures will include serial frailty evaluations (Clinical Frailty Scale and Groningen Frailty Indicator), functional assessments (hand grip strength and 4-meter walk test), muscle mass evaluations via computerized tomography morphometric analysis, and the evaluation of nutritional status via the analysis of urinary dietary biomarkers. The primary feasibility outcome is the estimation of the incidence rate of postoperative complications, and the primary clinical outcome is the association between the presence of postoperative complications and frailty, sarcopenia, and nutritional status. The secondary outcome measures are the length of hospital stay, 30-day hospital readmission rate, and mortality rate at days 30 and 90. ResultsOur study was approved by the National Health Service Research Ethics Committee (reference number: 19/WA/0190) via the Integrated Research Application System (project ID: 231694) prior to subject recruitment. Cardiff University is acting as the study sponsor. Our study is financially supported through an external, peer-reviewed grant from the British Geriatrics Society and internal funding resources from Cardiff University. The results will be disseminated through peer-review publications, social media, and conference proceedings. ConclusionsAs frailty, sarcopenia, and malnutrition are all areas of common derangement in the older surgical population, prospectively studying these risk factors in concert will allow for the analysis of their interplay as well as the development of predictive models for those at risk of commonly tracked surgical complications and outcomes. International Registered Report Identifier (IRRID)PRR1-10.2196/16846

Global navigation satellite systems (GNSSs) provide accurate positioning and timing services in a large gamut of sectors, including financial institutions, Industry 4.0, and Internet of things (IoT). Any industrial system involving multiple devices interacting and/or coordinating their functionalities needs accurate, dependable, and trustworthy time synchronization, which can be obtained by using authenticated GNSS signals. However, GNSS vulnerabilities to time-spoofing attacks may cause security issues for their applications. Galileo is currently developing new services aimed at providing increased security and robustness against attacks, such as the open service navigation message authentication (OS-NMA) and commercial authentication service (CAS). In this paper, we propose a robust and secure timing protocol that is independent of external time sources, and solely relies on assisted commercial authentication service (ACAS) and OS-NMA features. We analyze the performance of the proposed timing protocol and discuss its security level in relation to malicious attacks. Lastly, experimental tests were conducted to validate the proposed protocol.

HIV-1 transactivating factor Tat is released by infected cells. Extracellular Tat homodimerizes and engages several receptors, including integrins, vascular endothelial growth factor receptor 2 (VEGFR2) and heparan sulfate proteoglycan (HSPG) syndecan-1 expressed on various cells. By means of experimental cell models recapitulating the processes of lymphocyte trans-endothelial migration, here, we demonstrate that upon association with syndecan-1 expressed on lymphocytes, Tat triggers simultaneously the in cis activation of lymphocytes themselves and the in trans activation of endothelial cells (ECs). This “two-way” activation eventually induces lymphocyte adhesion and spreading onto the substrate and vascular endothelial (VE)-cadherin reorganization at the EC junctions, with consequent endothelial permeabilization, leading to an increased extravasation of Tat-presenting lymphocytes. By means of a panel of biochemical activation assays and specific synthetic inhibitors, we demonstrate that during the above-mentioned processes, syndecan-1, integrins, FAK, src and ERK1/2 engagement and activation are needed in the lymphocytes, while VEGFR2, integrin, src and ERK1/2 are needed in the endothelium. In conclusion, the Tat/syndecan-1 complex plays a central role in orchestrating the setup of the various in cis and in trans multimeric complexes at the EC/lymphocyte interface. Thus, by means of computational molecular modelling, docking and dynamics, we also provide a characterization at an atomic level of the binding modes of the Tat/heparin interaction, with heparin herein used as a structural analogue of the heparan sulfate chains of syndecan-1.

Background: Internationally, ready-to-eat breakfast cereals (RTEBC) make an important contribution to the nutritional intake of children. Significant differences have been found between the nutritional quality of children and non-children’s RTEBC. South Africa has strict legislation regarding the use of nutrition claims to promote products. Objectives: To determine i) differences in nutritional quality between children’s and non-children’s RTEBC; and, ii) compliance of nutrition claims with current legislation. Outcome measures: An analysis of the nutrient content per 100 g and per recommended serving size; an audit of nutrient content claims. Design: This study examined the packages of 134 RTEBC that were categorised into children’s cereal and six types of non-children’s cereal. Results: Children’s cereals formed 21% (n = 28) of the sample and were significantly more likely to have sugar as the first or second ingredient listed. Per 100 g, children’s cereals contained significantly more carbohydrates, sugar and sodium than non-children’s cereal collectively. Per 100 g and per serving, non-children’s cereal was significantly higher in protein, fat and dietary fibre compared to children’s cereal. Seventy-eight percent of all RTEBC (n = 104) had a nutrient content claim and 2% (n = 3) had a comparative claim. The most common claim was regarding dietary fibre (69 claims) followed by vitamins and minerals (65 claims). Ten nutrient claims were not compliant with legislation. Conclusion: Significant differences in nutritional quality exist between South African children’s and non-children’s RTEBC. Food manufacturers need to be more vigilant regarding nutrient claims and adhere to the labelling legislation.

Introduction Pharmacological interventions to address behavioural and psychological symptoms of dementia (BPSD) can have undesirable side effects, therefore non-pharmacological approaches to managing symptoms may be preferable. Past studies show that music therapy can reduce BPSD, and other studies have explored how formal caregivers use music in their caring roles. However, no randomised study has examined the effects on BPSD of music interventions delivered by informal caregivers (CGs) in the home setting. Our project aims to address the need for improved informal care by training cohabiting family CGs to implement music interventions that target BPSD, and the quality of life (QoL) and well-being of people with dementia (PwD) and CGs.Methods and analysis A large international three-arm parallel-group randomised controlled trial will recruit a sample of 495 dyads from Australia, Germany, UK, Poland and Norway. Dyads will be randomised equally to standard care (SC), a home-based music programme plus SC, or a home-based reading programme plus SC for 12 weeks. The primary outcome is BPSD of PwD (measured using the Neuropsychiatric Inventory-Questionnaire). Secondary outcomes will examine relationship quality between CG and PwD, depression, resilience, competence, QoL for CG and QoL for PwD. Outcomes will be collected at baseline, at the end of the 12-week intervention and at 6 months post randomisation. Resource Utilisation in Dementia will be used to collect economic data across the life of the intervention and at 6-month follow-up. We hypothesise that the music programme plus SC will generate better results than SC alone (primary comparison) and the reading programme plus SC (secondary comparison).Ethics and dissemination Ethical approval has been obtained for all countries. Results will be presented at national and international conferences and published in scientific journals and disseminated to consumer and caregiver representatives and the community.Trial registration numbers ACTRN12618001799246p; NCT03907748

Introduction Depression is a common disorder among older people living in residential aged care facilities. Several trials have demonstrated the effectiveness of behavioural therapies in treating depressive symptoms in older adults living in the community and in residential aged care. Behavioural Activation is demonstrably effective even when delivered by non-specialists (staff without formal psychological training), although strategies for adapting its use in residential aged care facilities are yet to be explored. This study will determine whether training residential care staff in the use of a structured Behavioural Activation programme is more effective at decreasing depressive symptoms among older residents than internet-based training about depression recognition and management alone.Method and analysis The behavioural activation in nursing homes to treat depression (BAN-Dep) trial is a pragmatic two-arm parallel clustered randomised controlled trial. It will recruit 666 residents aged 60 or older from 100 residential aged care facilities, which will be randomly assigned to the Behavioural Activation or control intervention. Staff in both treatment groups will be encouraged to complete the Beyondblue Professional Education to Aged Care e-learning programme to improve their recognition of and ability to respond to depression in older adults. Selected staff from intervention facilities will undergo additional training to deliver an 8-module Behavioural Activation programme to residents with subthreshold symptoms of depression-they will receive ongoing Mental support from trained Behavioural Activation therapists. Outcome measures will be collected by blind research officer at baseline and after 3, 6 and 12 months. The Patient Health Questionnaire-9 is the primary outcome measure of the study.Ethics and dissemination The trial will comply with the principles of the Declaration of Helsinki for Human Rights and is overseen by the University of Western Australia (reference RA/4/20/4234) and Melbourne Health (reference number HREC/18/MH/47) Ethics Committees. The results of this research project will be disseminated through publications and/or presentations in a variety of media to health professionals, academics, clinicians and the public. Only de-identified group data will be presented.Trial registration ACTRN12618000634279.

ObjectiveDelay in seeking diagnosis of dementia is common in China. Misinformation and poor knowledge about dementia may contribute to it. The study was designed to explore the nationwide dementia literacy among older adults in urban China and to investigate the factors associated with overall dementia literacy.MethodsIn a cross-sectional study, a convenience sample of 3,439 community-dwelling old adults aged 60 and over was recruited from 34 cities in 20 provinces between June 20 and August 20, 2014. All participants were administered the face-to-face mental health literacy questionnaire, which included the prevalence, symptoms, intention, and options for treatment of dementia. Stepwise multivariate regression analysis was used to explore factors associated with overall dementia literacy.ResultsThe response rate was 87.4%. The overall dementia literacy was 55.5% (SD = 20.9%) among all respondents. The correct response rate was higher for questions on symptoms (58.7–89.6%), but lower for questions on the prevalence (22.2%) and choosing appropriate professional care personnel (22.2%). Being male [OR = 1.256, 95% CI (1.022–1.543)], having lower per capita annual income [OR = 1.314, 95% CI (1.064–1.623)], lower education [OR = 1.462, 95% CI (1.162–1.839)], and suspected depression [OR = 1.248, 95% CI (1.009–1.543)] were negatively associated with overall dementia literacy.ConclusionDementia literacy among community-dwelling older adults in urban China remains very low, in particular about the impact of dementia and appropriate treatment personnel. Community educational programs aiming to close this knowledge gap are encouraged to focus on those in the population at highest risk of low dementia literacy.

Acetyl Coenzyme A-dependent N-, O- and N,O-acetylation of aromatic amines and hydrazines by arylamine N-acetyltransferases is well characterised. Here, we describe experiments demonstrating that human arylamine N-acetyltransferase Type 1 and its murine homologue (Type 2) can also catalyse the direct hydrolysis of acetyl Coenzyme A in the presence of folate. This folate-dependent activity is exclusive to these two isoforms; no acetyl Coenzyme A hydrolysis was found when murine arylamine N-acetyltransferase Type 1 or recombinant bacterial arylamine N-acetyltransferases were incubated with folate. Proton nuclear magnetic resonance spectroscopy allowed chemical modifications occurring during the catalytic reaction to be analysed in real time, revealing that the disappearance of acetyl CH3 from acetyl Coenzyme A occurred concomitantly with the appearance of a CH3 peak corresponding to that of free acetate and suggesting that folate is not acetylated during the reaction. We propose that folate is a cofactor for this reaction and suggest it as an endogenous function of this widespread enzyme. Furthermore, in silico docking of folate within the active site of human arylamine N-acetyltransferase Type 1 suggests that folate may bind at the enzyme's active site, and facilitate acetyl Coenzyme A hydrolysis. The evidence presented in this paper adds to our growing understanding of the endogenous roles of human arylamine N-acetyltransferase Type 1 and its mouse homologue and expands the catalytic repertoire of these enzymes, demonstrating that they are by no means just xenobiotic metabolising enzymes but probably also play an important role in cellular metabolism. These data, together with the characterisation of a naphthoquinone inhibitor of folate-dependent acetyl Coenzyme A hydrolysis by human arylamine N-acetyltransferase Type 1/murine arylamine N-acetyltransferase Type 2, open up a range of future avenues of exploration, both for elucidating the developmental role of these enzymes and for improving chemotherapeutic approaches to pathological conditions including estrogen receptor-positive breast cancer.

Human arylamine N-acetyltransferase 1 (hNAT1) has become an attractive potential biomarker for estrogen-receptor-positive breast cancers. We describe here the mechanism of action of a selective non-covalent colorimetric biosensor for the recognition of hNAT1 and its murine homologue, mNat2, over their respective isoenzymes, leading to new opportunities in diagnosis. On interaction with the enzyme, the naphthoquinone probe undergoes an instantaneous and striking visible color change from red to blue. Spectroscopic, chemical, molecular modelling and biochemical studies reported here show that the color change is mediated by selective recognition between the conjugate base of the sulfonamide group within the probe and the conjugate acid of the arginine residue within the active site of both hNAT1 and mNat2. This represents a new mechanism for selective biomarker sensing and may be exploited as a general approach to the specific detection of biomarkers in disease.