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Abstract Background Both exposure to air pollutants and obesity are associated with increased incidence and severity of COVID-19 infection; however, the mechanistic pathways involved are not well-characterized. After being primed by the transmembrane protease serine 2 (TMPRSS2) or furin protease, SARS-CoV-2 uses the angiotensin-converting enzyme (ACE)-2 receptor to enter respiratory epithelial cells. The androgen receptor (AR) is known to regulate both TMPRSS2 and ACE2 expression, and neuropilin-1 (NRP1) is a proposed coreceptor for SARS-CoV-2; thus, altered expression of these factors may promote susceptibility to infection. As such, this study investigated the hypothesis that inhalational exposure to traffic-generated particulate matter (diesel exhaust particulate; DEP) increases the expression of those pathways that mediate SARS-CoV-2 infection and susceptibility, which is exacerbated by the consumption of a high-fat (HF) diet. Methods Four- to six-week-old male C57BL/6 mice fed either regular chow or a HF diet (HF, 45% kcal from fat) were randomly assigned to be exposed via oropharyngeal aspiration to 35 µg DEP suspended in 35 µl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. Furthermore, as previous studies have shown that probiotic treatment can protect against exposure-related inflammatory outcomes in the lungs, a subset of study animals fed a HF diet were concurrently treated with 0.3 g/day Winclove Ecologic® Barrier probiotics in their drinking water throughout the study. Results Our results revealed that the expression of ACE2 protein increased with DEP exposure and that TMPRSS2, AR, NRP1, and furin protein expression increased with DEP exposure in conjunction with a HF diet. These DEP ± HF diet-mediated increases in expression were mitigated with probiotic treatment. Conclusion These findings suggest that inhalational exposure to air pollutants in conjunction with the consumption of a HF diet contributes to a more susceptible lung environment to SARS-CoV-2 infection and that probiotic treatment could be beneficial as a preventative measure.

Abstract Background The gut microbiota plays a vital role in host homeostasis and is associated with inflammation and cardiovascular disease (CVD) risk. Exposure to particulate matter (PM) is a known mediator of inflammation and CVD and is reported to promote dysbiosis and decreased intestinal integrity. However, the role of inhaled traffic-generated PM on the gut microbiome and its corresponding systemic effects are not well-characterized. Thus, we investigated the hypothesis that exposure to inhaled diesel exhaust particles (DEP) alters the gut microbiome and promotes microbial-related inflammation and CVD biomarkers. 4–6-week-old male C57Bl/6 mice on either a low-fat (LF, 10% fat) or high-fat (HF, 45% fat) diet were exposed via oropharyngeal aspiration to 35 μg DEP suspended in 35 μl saline or saline only (CON) 2x/week for 30 days. To determine whether probiotics could prevent diet or DEP exposure mediated alterations in the gut microbiome or systemic outcomes, a subset of animals on the HF diet were treated orally with 0.3 g/day (~ 7.5 × 108 CFU/day) of Winclove Ecologic® Barrier probiotics throughout the study. Results Our results show that inhaled DEP exposure alters gut microbial profiles, including reducing Actinobacteria and expanding Verrucomicrobia and Proteobacteria. We observed increased circulating LPS, altered circulating cytokines (IL-1α, IL-3, IL-13, IL-15, G-CSF, LIF, MIP-2, and TNF-α), and CVD biomarkers (siCAM, PAI-1, sP-Selectin, thrombomodulin, and PECAM) in DEP-exposed and/or HF diet mice. Furthermore, probiotics attenuated the observed reduction of Actinobacteria and expansion of Proteobacteria in DEP-exposed and HF-diet mice. Probiotics mitigated circulating cytokines (IL-3, IL-13, G-CSF, RANTES, and TNF- α) and CVD biomarkers (siCAM, PAI-1, sP-Selectin, thrombomodulin, and PECAM) in respect to DEP-exposure and/or HF diet. Conclusion Key findings of this study are that inhaled DEP exposure alters small intestinal microbial profiles that play a role in systemic inflammation and early CVD biomarkers. Probiotic treatment in this study was fundamental in understanding the role of inhaled DEP on the microbiome and related systemic inflammatory and CVD biomarkers.

Abstract Background Exposure to traffic-generated emissions is associated with the development and exacerbation of inflammatory lung disorders such as chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF). Although many lung diseases show an expansion of Proteobacteria, the role of traffic-generated particulate matter pollutants on the lung microbiota has not been well-characterized. Thus, we investigated the hypothesis that exposure to diesel exhaust particles (DEP) can alter commensal lung microbiota, thereby promoting alterations in the lung’s immune and inflammatory responses. We aimed to understand whether diet might also contribute to the alteration of the commensal lung microbiome, either alone or related to exposure. To do this, we used male C57Bl/6 mice (4–6-week-old) on either regular chow (LF) or high-fat (HF) diet (45% kcal fat), randomly assigned to be exposed via oropharyngeal aspiration to 35 μg DEP, suspended in 35 μl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. A separate group of study animals on the HF diet was concurrently treated with 0.3 g/day of Winclove Ecologic® Barrier probiotics in their drinking water throughout the study. Results Our results show that DEP-exposure increases lung tumor necrosis factor (TNF)-α, interleukin (IL)-10, Toll-like receptor (TLR)-2, TLR-4, and the nuclear factor kappa B (NF-κB) histologically and by RT-qPCR, as well as Immunoglobulin A (IgA) and Immunoglobulin G (IgG) in the bronchoalveolar lavage fluid (BALF), as quantified by ELISA. We also observed an increase in macrophage infiltration and peroxynitrite, a marker of reactive oxygen species (ROS) + reactive nitrogen species (RNS), immunofluorescence staining in the lungs of DEP-exposed and HF-diet animals, which was further exacerbated by concurrent DEP-exposure and HF-diet consumption. Histological examinations revealed enhanced inflammation and collagen deposition in the lungs DEP-exposed mice, regardless of diet. We observed an expansion of Proteobacteria, by qPCR of bacterial 16S rRNA, in the BALF of DEP-exposed mice on the HF diet, which was diminished with probiotic-treatment. Conclusions Our findings suggest that exposure to DEP causes persistent and sustained inflammation and bacterial alterations in a ROS-RNS mediated fashion, which is exacerbated by concurrent consumption of an HF diet.

Agricultural areas can benefit from the reduction of rodents by raptors, yet many croplands and pastures do not provide adequate perching structures needed by raptors to hunt effectively. Many artificial raptor perches have been constructed as a solution to this deficiency, however, monitoring the benefits of these perches has proved challenging. We developed a method using artificial perches and camera traps mounted on poles that allows for 24-hour monitoring of perch utilization. We tested the new method in an agricultural area in northern California and demonstrated its ability to facilitate accurate species identification and to quantify raptor use and activity. Three of the six raptor species observed at the site utilized the artificial perches: American kestrels (Falco sparverius), red-tailed hawks (Buteo jamaicensis), and red-shouldered hawks (B. lineatus). We did not document any rodent predation events from the perches; but we did observe American kestrels using perches to hunt for invertebrates. Overall, we found that using camera traps mounted on poles can successfully monitor artificial perches and can be easily used to study the effectiveness of hunting perches for raptors in agricultural areas.

Air pollution has been documented to contribute to severe respiratory diseases like asthma and chronic obstructive pulmonary disorder (COPD). Although these diseases demonstrate a shift in the lung microbiota towards Proteobacteria, the effects of traffic generated emissions on lung microbiota profiles have not been well-characterized. Thus, we investigated the hypothesis that exposure to traffic-generated emissions can alter lung microbiota and immune defenses. Since a large population of the Western world consumes a diet rich in fats, we sought to investigate the synergistic effects of mixed vehicle emissions and high-fat diet consumption. We exposed 3-month-old male C57Bl/6 mice placed either on regular chow (LF) or a high-fat (HF: 45% kcal fat) diet to mixed emissions (ME: 30 µg PM/m3 gasoline engine emissions+70 µg PM/m3 diesel engine emissions) or filtered air (FA) for 6 h/d, 7 d/wk for 30 days. Levels of pulmonary immunoglobulins IgA, IgG, and IgM were analyzed by ELISA, and lung microbial profiling was done using qPCR and Illumina 16 S sequencing. We observed a significant decrease in lung IgA in the ME-exposed animals, compared to the FA-exposed animals, both fed a HF diet. Our results also revealed a significant decrease in lung IgG in the ME-exposed animals both on the LF diet and HF diet, in comparison to the FA-exposed animals. We also observed an expansion of Enterobacteriaceae belonging to the Proteobacteria phylum in the ME-exposed groups on the HF diet. Collectively, we show that the combined effects of ME and HF diet result in decreased immune surveillance and lung bacterial dysbiosis, which is of significance in lung diseases.

Epidemiological studies reveal a correlation between air pollution exposure and gastrointestinal (GI) diseases, yet few studies have investigated the role of inhaled particulate matter on intestinal integrity in conjunction with a high-fat (HF) diet. Additionally, there is currently limited information on probiotics in mitigating air-pollutant responses in the intestines. Thus, we investigated the hypothesis that exposure to inhaled diesel exhaust particles (DEP) and a HF diet can alter intestinal integrity and inflammation, which can be attenuated with probiotics. 4–6-w-old male C57Bl/6 mice on a HF diet (45% kcal fat) were randomly assigned to be exposed via oropharyngeal aspiration to 35 µg of DEP suspended in 35 µL of 0.9% sterile saline or sterile saline (CON) only twice a week for 4 w. A subset of mice was treated with 0.3 g/day of Winclove Ecologic® barrier probiotics (PRO) in drinking water throughout the duration of the study. Our results show that DEP exposure ± probiotics resulted in increased goblet cells and mucin (MUC)-2 expression, as determined by AB/PAS staining. Immunofluorescent quantification and/or RT-qPCR showed that DEP exposure increases claudin-3, occludin, zona occludens (ZO)-1, matrix metalloproteinase (MMP)-9, and toll-like receptor (TLR)-4, and decreases tumor necrosis factor (TNF)-α and interleukin (IL)-10 expression compared to CON. DEP exposure + probiotics increases expression of claudin-3, occludin, ZO-1, TNF-α, and IL-10 and decreases MMP-9 and TLR-4 compared to CON + PRO in the small intestine. Collectively, these results show that DEP exposure alters intestinal integrity and inflammation in conjunction with a HF diet. Probiotics proved fundamental in understanding the role of the microbiome in protecting and altering inflammatory responses in the intestines following exposure to inhaled DEP.

Introduction Workplace features such as ventilation, temperature and the extent of contact are all likely to relate to personal risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Occupations relating to healthcare, social care, education, transport and food production and retail are thought to have increased risks, but the extent to which these risks are elevated and how they have varied over time is unclear. Methods We searched for population cohort studies conducted in Europe that compared coronavirus disease 2019 (COVID-19) outcomes between two or more different occupational groups. Data were extracted on relative differences between occupational groups, split into four time-periods corresponding to pandemic waves. Results We included data from 17 studies. 11 studies used SARS-CoV-2 as their outcome measure and six used COVID-19 hospitalisation and mortality. During waves one and two, the majority of studies saw elevated risks in the five groups that we looked at. Only seven studies used data from wave three onwards. Elevated risks were observed in waves three and four for social care and education workers in some studies. Conclusions Evidence relating to occupational differences in COVID-19 outcomes in Europe largely focuses on the early part of the pandemic. There is consistent evidence that the direction and magnitude of differences varied with time. Workers in the healthcare, transport and food production sectors saw highly elevated risks in the early part of the pandemic in the majority of studies but this did not appear to continue. There was evidence that elevated risks of infection in the education and social care sectors may have persisted.

BackgroundMarkerless motion capture (MMC) uses video cameras or depth sensors for full body tracking and presents a promising approach for objectively and unobtrusively monitoring functional performance within community settings, to aid clinical decision-making in neurodegenerative diseases such as dementia. ObjectiveThe primary objective of this systematic review was to investigate the application of MMC using full-body tracking, to quantify functional performance in people with dementia, mild cognitive impairment, and Parkinson disease. MethodsA systematic search of the Embase, MEDLINE, CINAHL, and Scopus databases was conducted between November 2022 and February 2023, which yielded a total of 1595 results. The inclusion criteria were MMC and full-body tracking. A total of 157 studies were included for full-text screening, out of which 26 eligible studies that met the selection criteria were included in the review. ResultsPrimarily, the selected studies focused on gait analysis (n=24), while other functional tasks, such as sit to stand (n=5) and stepping in place (n=1), were also explored. However, activities of daily living were not evaluated in any of the included studies. MMC models varied across the studies, encompassing depth cameras (n=18) versus standard video cameras (n=5) or mobile phone cameras (n=2) with postprocessing using deep learning models. However, only 6 studies conducted rigorous comparisons with established gold-standard motion capture models. ConclusionsDespite its potential as an effective tool for analyzing movement and posture in individuals with dementia, mild cognitive impairment, and Parkinson disease, further research is required to establish the clinical usefulness of MMC in quantifying mobility and functional performance in the real world.

One of the main priorities of the Integrated Care Systems (ICS) is to expand the number of ‘virtual wards’ and deliver multidisciplinary care for patients closer to home. We present to you the Specialist Neurological Rehabilitation Service (SNRS) which has demonstrated over the last 7 years that intensive neurological rehabilitation can be delivered successfully in the patients’ own homes. A novel commissioning model has been used in partnership with different NHS trusts to provide a unified neurorehabilitation service with both inpatient hospital beds and virtual beds in the patients’ own homes. While patients are on the virtual bed pathway, they remain under the care of the Consultant in Rehabilitation Medicine with support from the Clinical Nurse Specialist and have access to diagnostics/interventions and clinic reviews. The patients get daily intensive MDT therapy input from the skilled community team who provide the same frequency of therapy sessions at home (as they would get in a level 2 inpatient neurorehabilitation unit). This pathway is supporting the earlier discharge of patients from hospital. Additionally, the analysis of data from the virtual bed pathway shows that rehabilitation outcomes in patients’ own homes are similar to those of bedded units for this subset of patients with complex neurological needs. This illustrates that the virtual ward model can be successfully implemented in neurorehabilitation.

Abstract Urinary Tract Infections (UTIs) are one of the most prevalent bacterial infections in older adults and a significant contributor to unplanned hospital admissions in People Living with Dementia (PLWD), with early detection being crucial due to the predicament of reporting symptoms and limited help-seeking behaviour. The most common diagnostic tool is urine sample analysis, which can be time-consuming and is only employed where UTI clinical suspicion exists. In this method development and proof-of-concept study, participants living with dementia were monitored via low-cost devices in the home that passively measure activity, sleep, and nocturnal physiology. Using 27828 person-days of remote monitoring data (from 117 participants), we engineered features representing symptoms used for diagnosing a UTI. We then evaluate explainable machine learning techniques in passively calculating UTI risk and perform stratification on scores to support clinical translation and allow control over the balance between alert rate and sensitivity and specificity. The proposed UTI algorithm achieves a sensitivity of 65.3% (95% Confidence Interval (CI) = 64.3–66.2) and specificity of 70.9% (68.6–73.1) when predicting UTIs on unseen participants and after risk stratification, a sensitivity of 74.7% (67.9–81.5) and specificity of 87.9% (85.0–90.9). In addition, feature importance methods reveal that the largest contributions to the predictions were bathroom visit statistics, night-time respiratory rate, and the number of previous UTI events, aligning with the literature. Our machine learning method alerts clinicians of UTI risk in subjects, enabling earlier detection and enhanced screening when considering treatment.

BackgroundTechnology-related research on people with dementia and their carers often aims to enable people to remain living at home for longer and prevent unnecessary hospital admissions. To develop person-centered, effective, and ethical research, patient and public involvement (PPI) is necessary, although it may be perceived as more difficult with this cohort. With recent and rapid expansions in health and care–related technology, this review explored how and with what impact collaborations between researchers and stakeholders such as people with dementia and their carers have taken place. ObjectiveThis review aims to describe approaches to PPI used to date in technology-related dementia research, along with the barriers and facilitators and impact of PPI in this area. MethodsA scoping review of literature related to dementia, technology, and PPI was conducted using MEDLINE, PsycINFO, Embase, and CINAHL. Papers were screened for inclusion by 2 authors. Data were then extracted using a predesigned data extraction table by the same 2 authors. A third author supported the resolution of any conflicts at each stage. Barriers to and facilitators of undertaking PPI were then examined and themed. ResultsThe search yielded 1694 papers, with 31 (1.83%) being analyzed after screening. Most (21/31, 68%) did not make clear distinctions between activities undertaken as PPI and those undertaken by research participants, and as such, their involvement did not fit easily into the National Institute for Health and Care Research definition of PPI. Most of this mixed involvement focused on reviewing or evaluating technology prototypes. A range of approaches were described, most typically using focus groups or co-design workshops. In total, 29% (9/31) described involvement at multiple stages throughout the research cycle, sometimes with evidence of sharing decision-making power. Some (23/31, 74%) commented on barriers to or facilitators of effective PPI. The challenges identified often regarded issues of working with people with significant cognitive impairments and pressures on time and resources. Where reported, the impact of PPI was largely reported as positive, including the experiences for patient and public partners, the impact on research quality, and the learning experience it provided for researchers. Only 4 (13%) papers used formal methods for evaluating impact. ConclusionsResearchers often involve people with dementia and other stakeholders in technology research. At present, involvement is often limited in scope despite aspirations for high levels of involvement and partnership working. Involving people with dementia, their carers, and other stakeholders can have a positive impact on research, patient and public partners, and researchers. Wider reporting of methods and facilitative strategies along with more formalized methods for recording and reporting on meaningful impact would be helpful so that all those involved—researchers, patients, and other stakeholders—can learn how we can best conduct research together.

Objectives: The purpose of this study was to explore the information needs and preferences of adolescent and young adult (AYA) cancer patients to guide next steps for development of a new online resource for this audience. The goals were to understand information needs, prioritize topic areas, and inform website design and functionality. Methods: Participants were AYA cancer patients ages 13–25 years. We used multiple methods in two phases to gather audience feedback. The first phase collected quantitative data in an electronic survey (n = 45) about AYA patients' internet use and content preferences. The second phase collected qualitative data through focus groups (n = 13) about user preferences for content design and website function. Results: Survey results showed AYA patients were more interested in content about how treatments would impact their lives rather than the treatments themselves. They preferred content on school, careers, relationships, independence, side effects, and fertility. The focus groups indicated AYA patients prefer a clean, stylish design; infographics and visual aids; and the ability to find information quickly and control the amount they read. Conclusions: Online resources represent an important opportunity to advance cancer education for AYA patients. However, it is important to consider the information needs and preferences of this audience in content design and delivery. Innovation: Practitioners should use stakeholder input to guide the creation of patient education resources that are age- and audience-appropriate. This study provides insights into AYA information needs and preferences in pediatric oncology.

Abstract The COVID-19 pandemic has dramatically altered the behaviour of most of the world’s population, particularly affecting the elderly, including people living with dementia (PLwD). Here we use remote home monitoring technology deployed into 31 homes of PLwD living in the UK to investigate the effects of COVID-19 on behaviour within the home, including social isolation. The home activity was monitored continuously using unobtrusive sensors for 498 days from 1 December 2019 to 12 April 2021. This period included six distinct pandemic phases with differing public health measures, including three periods of home ‘lockdown’. Linear mixed-effects modelling is used to examine changes in the home activity of PLwD who lived alone or with others. An algorithm is developed to quantify time spent outside the home. Increased home activity is observed from very early in the pandemic, with a significant decrease in the time spent outside produced by the first lockdown. The study demonstrates the effects of COVID-19 lockdown on home behaviours in PLwD and shows how unobtrusive home monitoring can be used to track behaviours relevant to social isolation.

BackgroundSleep disorders are common among the aging population and people with neurodegenerative diseases. Sleep disorders have a strong bidirectional relationship with neurodegenerative diseases, where they accelerate and worsen one another. Although one-to-one individual cognitive behavioral interventions (conducted in-person or on the internet) have shown promise for significant improvements in sleep efficiency among adults, many may experience difficulties accessing interventions with sleep specialists, psychiatrists, or psychologists. Therefore, delivering sleep intervention through an automated chatbot platform may be an effective strategy to increase the accessibility and reach of sleep disorder intervention among the aging population and people with neurodegenerative diseases. ObjectiveThis work aims to (1) determine the feasibility and usability of an automated chatbot (named MotivSleep) that conducts sleep interviews to encourage the aging population to report behaviors that may affect their sleep, followed by providing personalized recommendations for better sleep based on participants’ self-reported behaviors; (2) assess the self-reported sleep assessment changes before, during, and after using our automated sleep disturbance intervention chatbot; (3) assess the changes in objective sleep assessment recorded by a sleep tracking device before, during, and after using the automated chatbot MotivSleep. MethodsWe will recruit 30 older adult participants from West London for this pilot study. Each participant will have a sleep analyzer installed under their mattress. This contactless sleep monitoring device passively records movements, heart rate, and breathing rate while participants are in bed. In addition, each participant will use our proposed chatbot MotivSleep, accessible on WhatsApp, to describe their sleep and behaviors related to their sleep and receive personalized recommendations for better sleep tailored to their specific reasons for disrupted sleep. We will analyze questionnaire responses before and after the study to assess their perception of our proposed chatbot; questionnaire responses before, during, and after the study to assess their subjective sleep quality changes; and sleep parameters recorded by the sleep analyzer throughout the study to assess their objective sleep quality changes. ResultsRecruitment will begin in May 2023 through UK Dementia Research Institute Care Research and Technology Centre organized community outreach. Data collection will run from May 2023 until December 2023. We hypothesize that participants will perceive our proposed chatbot as intelligent and trustworthy; we also hypothesize that our proposed chatbot can help improve participants’ subjective and objective sleep assessment throughout the study. ConclusionsThe MotivSleep automated chatbot has the potential to provide additional care to older adults who wish to improve their sleep in more accessible and less costly ways than conventional face-to-face therapy. International Registered Report Identifier (IRRID)PRR1-10.2196/45752

Introduction The prevalence of traumatic brain injury (TBI) among older adults is increasing exponentially. The sequelae can be severe in older adults and interact with age-related conditions such as multimorbidity. Despite this, TBI research in older adults is sparse. Minder, an in-home monitoring system developed by the UK Dementia Research Institute Centre for Care Research and Technology, uses infrared sensors and a bed mat to passively collect sleep and activity data. Similar systems have been used to monitor the health of older adults living with dementia. We will assess the feasibility of using this system to study changes in the health status of older adults in the early period post-TBI.Methods and analysis The study will recruit 15 inpatients (>60 years) with a moderate-severe TBI, who will have their daily activity and sleep patterns monitored using passive and wearable sensors over 6 months. Participants will report on their health during weekly calls, which will be used to validate sensor data. Physical, functional and cognitive assessments will be conducted across the duration of the study. Activity levels and sleep patterns derived from sensor data will be calculated and visualised using activity maps. Within-participant analysis will be performed to determine if participants are deviating from their own routines. We will apply machine learning approaches to activity and sleep data to assess whether the changes in these data can predict clinical events. Qualitative analysis of interviews conducted with participants, carers and clinical staff will assess acceptability and utility of the system.Ethics and dissemination Ethical approval for this study has been granted by the London-Camberwell St Giles Research Ethics Committee (REC) (REC number: 17/LO/2066). Results will be submitted for publication in peer-reviewed journals, presented at conferences and inform the design of a larger trial assessing recovery after TBI.

BackgroundInternet of Things (IoT) technology enables physiological measurements to be recorded at home from people living with dementia and monitored remotely. However, measurements from people with dementia in this context have not been previously studied. We report on the distribution of physiological measurements from 82 people with dementia over approximately 2 years. ObjectiveOur objective was to characterize the physiology of people with dementia when measured in the context of their own homes. We also wanted to explore the possible use of an alerts-based system for detecting health deterioration and discuss the potential applications and limitations of this kind of system. MethodsWe performed a longitudinal community-based cohort study of people with dementia using “Minder,” our IoT remote monitoring platform. All people with dementia received a blood pressure machine for systolic and diastolic blood pressure, a pulse oximeter measuring oxygen saturation and heart rate, body weight scales, and a thermometer, and were asked to use each device once a day at any time. Timings, distributions, and abnormalities in measurements were examined, including the rate of significant abnormalities (“alerts”) defined by various standardized criteria. We used our own study criteria for alerts and compared them with the National Early Warning Score 2 criteria. ResultsA total of 82 people with dementia, with a mean age of 80.4 (SD 7.8) years, recorded 147,203 measurements over 958,000 participant-hours. The median percentage of days when any participant took any measurements (ie, any device) was 56.2% (IQR 33.2%-83.7%, range 2.3%-100%). Reassuringly, engagement of people with dementia with the system did not wane with time, reflected in there being no change in the weekly number of measurements with respect to time (1-sample t-test on slopes of linear fit, P=.45). A total of 45% of people with dementia met criteria for hypertension. People with dementia with α-synuclein–related dementia had lower systolic blood pressure; 30% had clinically significant weight loss. Depending on the criteria used, 3.03%-9.46% of measurements generated alerts, at 0.066-0.233 per day per person with dementia. We also report 4 case studies, highlighting the potential benefits and challenges of remote physiological monitoring in people with dementia. These include case studies of people with dementia developing acute infections and one of a person with dementia developing symptomatic bradycardia while taking donepezil. ConclusionsWe present findings from a study of the physiology of people with dementia recorded remotely on a large scale. People with dementia and their carers showed acceptable compliance throughout, supporting the feasibility of the system. Our findings inform the development of technologies, care pathways, and policies for IoT-based remote monitoring. We show how IoT-based monitoring could improve the management of acute and chronic comorbidities in this clinically vulnerable group. Future randomized trials are required to establish if a system like this has measurable long-term benefits on health and quality of life outcomes.

ObjectiveWe aimed to use mathematical models of SARS-COV-2 to assess the potential efficacy of non-pharmaceutical interventions on transmission in the parcel delivery and logistics sector.MethodsWe devloped a network-based model of workplace contacts based on data and consultations from companies in the parcel delivery and logistics sectors. We used these in stochastic simulations of disease transmission to predict the probability of workplace outbreaks in this settings. Individuals in the model have different viral load trajectories based on SARS-CoV-2 in-host dynamics, which couple to their infectiousness and test positive probability over time, in order to determine the impact of testing and isolation measures.ResultsThe baseline model (without any interventions) showed different workplace infection rates for staff in different job roles. Based on our assumptions of contact patterns in the parcel delivery work setting we found that when a delivery driver was the index case, on average they infect only 0.14 other employees, while for warehouse and office workers this went up to 0.65 and 2.24 respectively. In the LIDD setting this was predicted to be 1.40, 0.98, and 1.34 respectively. Nonetheless, the vast majority of simulations resulted in 0 secondary cases among customers (even without contact-free delivery). Our results showed that a combination of social distancing, office staff working from home, and fixed driver pairings (all interventions carried out by the companies we consulted) reduce the risk of workplace outbreaks by 3-4 times.ConclusionThis work suggests that, without interventions, significant transmission could have occured in these workplaces, but that these posed minimal risk to customers. We found that identifying and isolating regular close-contacts of infectious individuals (i.e. house-share, carpools, or delivery pairs) is an efficient measure for stopping workplace outbreaks. Regular testing can make these isolation measures even more effective but also increases the number of staff isolating at one time. It is therefore more efficient to use these isolation measures in addition to social distancing and contact reduction interventions, rather than instead of, as these reduce both transmission and the number of people needing to isolate at one time.

Abstract Background The hepatitis E virus (HEV) infection has been described as a causing factor for acute-on-chronic-liver-failure (ACLF) in patients with underlying chronic liver disease (CLD), such as chronic hepatitis or cirrhosis, which could end in the failure of one or more organs and high short-term mortality. There are scarce data about the association of HEV in patients with chronic liver disorders in South America. Case presentation A 56-year-old hypertensive male with a history of type 2 diabetes was diagnosed with alcohol-related-liver cirrhosis in February 2019. A year later, the patient was admitted to hospital due to fatigue, jaundice and acholia. No evidence of hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein–Barr virus, herpes zoster virus and cytomegalovirus infections were found. Nevertheless, in February and March, 2020 the patient was positive for HEV-IgM and HEV-IgG, and HEV genotype 3 RNA was detected in sera. Afterwards, he presented grade I hepatic encephalopathy and, therefore, was diagnosed with acute hepatitis E-on-chronic liver disease. The patient reported a recent travel to the Argentine coast, where he consumed seafood. Besides, he reveled to have consumed pork meat and had no history of blood transfusion. Conclusion This report describes a unique case of hepatitis E virus infection in a patient with alcohol-related cirrhosis. This is the first report of a patient with HEV-related ACLF in Argentina and it invokes the importance of HEV surveillance and treatment among patients with CLD, such as alcohol-related cirrhosis.

BackgroundThe number of people with dementia is expected to grow worldwide. Among the ways to support both persons with early-stage dementia and their caregivers (dyads), researchers are studying mindfulness interventions. However, few studies have explored technology-enhanced mindfulness interventions for dyads and the needs of persons with dementia and their caregivers. ObjectiveThe main aim of this study was to elicit essential needs from people with dementia, their caregivers, dementia experts, and mindfulness experts to identify themes that can be used in the design of mindfulness conversational agents for dyads. MethodsSemistructured interviews were conducted with 5 dementia experts, 5 mindfulness experts, 5 people with early-stage dementia, and 5 dementia caregivers. Interviews were transcribed and coded on NVivo (QSR International) before themes were identified through a bottom-up inductive approach. ResultsThe results revealed that dyadic mindfulness is preferred and that implementation formats such as conversational agents have potential. A total of 5 common themes were also identified from expert and user feedback, which should be used to design mindfulness conversational agents for persons with dementia and their caregivers. The 5 themes included enhancing accessibility, cultivating positivity, providing simplified tangible and thought-based activities, encouraging a mindful mindset shift, and enhancing relationships. ConclusionsIn essence, this research concluded with 5 themes that mindfulness conversational agents could be designed based on to meet the needs of persons with dementia and their caregivers.

Abstract Background Workplace transmission is a significant contributor to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks. Previous studies have found that infectious illness presenteeism could contribute to outbreaks in occupational settings and identified multiple occupational and organisational risk factors. Amid the COVID-19 pandemic, it is imperative to investigate presenteeism particularly in relation to respiratory infectious disease (RID). Hence, this rapid review aims to determine the prevalence of RID-related presenteeism, including COVID-19, and examines the reported reasons and associated risk factors. Methods The review followed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search approach and focused on studies published in English and Chinese. Database searches included MEDLINE, EMBASE, Web of Science, China Knowledge Resource Integrated Database (CNKI) and preprint databases MedRxiv and BioRxiv. Results The search yielded 54 studies, of which four investigated COVID-19-related presenteeism. Prevalence of work presenteeism ranged from 14.1 to 55% for confirmed RID, and 6.6 to 100% for those working with suspected or subclinical RID. The included studies demonstrated that RID-related presenteeism is associated with occupation, sick pay policy, age, gender, health behaviour and perception, vaccination, peer pressure and organisational factors such as presenteeism culture. Conclusions This review demonstrates that presenteeism or non-adherence to isolation guidance is a real concern and can contribute to workplace transmissions and outbreaks. Policies which would support workers financially and improve productivity, should include a range of effective non-pharmaceutical inventions such as workplace testing, promoting occupational health services, reviewing pay and bonus schemes and clear messaging to encourage workers to stay at home when ill. Future research should focus on the more vulnerable and precarious occupational groups, and their inter-relationships, to develop comprehensive intervention programs to reduce RID-related presenteeism.

BackgroundThe incidence of thrombotic complications is high in COVID-19 patients with severe disease. As key regulators of thrombus formation, platelets likely play a crucial role as mediators of severe acute respiratory syndrome coronavirus 2 associated pathogenesis. Studies have reported that parameters reflecting platelet size, known as platelet volume indices (PVI), are raised in patients with thrombosis and can predict poor outcomes. This systematic review evaluates the potential for PVI to be used as a predictor of COVID-19 morbidity and mortality.MethodsEnglish and Chinese databases were searched electronically to identify studies reporting data on mean platelet volume, platelet distribution width or platelet-large cell ratio in COVID-19 patients. Included articles underwent a quality rating and descriptive narrative analysis.ResultsThirty-two studies were included in the systematic review. The results show a general trend for PVI to be raised in severe COVID-19 patients and non-survivors, with 14 studies reporting significant differences of baseline PVI between severe and mild disease. Nonetheless, longitudinal studies showed varying PVI trends over the course of the disease and evidence for PVI to be associated with disease progression was limited. The quality rating of 12 studies was poor, 16 were rated fair and four were good. Most studies were retrospective in design, used small study populations and did not consider confounding factors that influence platelet volume. Studies also contained technical flaws in PVI measurement, limiting the reliability of the results.ConclusionThe evidence on the clinical usefulness of PVI is greatly limited by the lack of prospective evaluation, together with technical problems in measuring PVI. Carefully designed prospective studies are warranted.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=304305, identifier CRD42022304305.

BackgroundThe emergence of SARS-CoV-2 triggered a chain of public health responses that radically changed our way of living and working. Non-healthcare sectors, such as the logistics sector, play a key role in such responses. This research aims to qualitatively evaluate the non-pharmaceutical interventions (NPIs) implemented in the UK logistics sector during the COVID-19 pandemic.MethodsWe conducted nine semi-structured interviews in July-August 2020 and May-June 2021. In total 11 interviewees represented six companies occupying a range of positions in the UK's logistics sector, including takeaway food delivery, large and small goods delivery and home appliance installation, and logistics technology providers. Thematic analysis was completed using NVivo12. Codes relevant to NPIs were grouped into themes and mapped deductively onto an adapted Hierarchy of Control (HoC) framework, focusing on delivery workers. Codes relevant to the implementation process of NPIs were grouped into themes/subthemes to identify key characteristics of rapid responses, and barriers and facilitators.ResultsHoC analysis suggests the sector has implemented a wide range of risk mitigation measures, with each company developing their own portfolio of measures. Contact-free delivery was the most commonly implemented measure and perceived effective. The other implemented measures included social distancing, internal contact tracing, communication and collaboration with other key stakeholders of the sector. Process evaluation identified facilitators of rapid responses including capacity to develop interventions internally, localized government support, strong external mandates, effective communication, leadership support and financial support for self-isolation, while barriers included unclear government guidance, shortage of testing capacity and supply, high costs and diversified language and cultural backgrounds. Main sustainability issues included compliance fatigue, and the possible mental health impacts of a prolonged rapid response.ConclusionsThis research identified drivers and obstacles of rapid implementation of NPIs in response to a respiratory infection pandemic. Existing implementation process models do not consider speed to respond and the absence or lack of guidance in emergency situations such as the COVID-19. We recommend the development of a rapid response model to inform the design of effective and sustainable infection prevention and control policies and to focus future research priorities.

Introduction Prehabilitation in colorectal surgery is evolving and may minimise postoperative morbidity and mortality. With many different healthcare professionals contributing to the prehabilitation literature, there is significant variation in reported primary endpoints that restricts comparison. In addition, there has been limited work on patient-related outcome measures suggesting that patients with colorectal cancer needs and issues are being overlooked. The Defining Standards in Colorectal Optimisation Study aims to achieve international consensus from all stakeholders on key standards to provide a framework for reporting future prehabilitation research.Methods and analysis A systematic review will identify key standards reported in trials of prehabilitation in colorectal surgery. Standards that are important to patients will be identified by a patient and public involvement (PPI) event. The longlist of standards generated from the systematic review and PPI event will be used to develop a three-round online Delphi process. This will engage all stakeholders (healthcare professionals and patients) both nationally and internationally. The results of the Delphi will be followed by a face-to-face interactive consensus meeting that will define the final standards for prehabilitation for elective colorectal surgery.Ethics and dissemination The University of Glasgow College of Medical, Veterinary and Life Sciences Ethics Committee has approved this protocol, which is registered as a study (200190120) with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of the standards developed by all stakeholders will increase the potential for comparative research that advances understanding of the clinical application of prehabilitation.PROSPERO registration number CRD42019120381.

Immune tolerance and response are both largely driven by the interactions between the major histocompatibility complex (MHC) expressed by antigen presenting cells (APCs), T-cell receptors (TCRs) on T-cells, and their cognate antigens. Disordered interactions cause the pathogenesis of autoimmune diseases such as type 1 diabetes. Therefore, the identification of antigenic epitopes of autoreactive T-cells leads to important advances in therapeutics and biomarkers. Next-generation sequencing methods allow for the rapid identification of thousands of TCR clonotypes from single T-cells, and thus there is a need to determine cognate antigens for identified TCRs. This protocol describes a reporter system of T-cell activation where the fluorescent reporter protein ZsGreen-1 is driven by nuclear factor of activated T-cells (NFAT) signaling and read by flow cytometry. Reporter T-cells also constitutively express additional pairs of fluorescent proteins as identifiers, allowing for multiplexing of up to eight different reporter T-cell lines simultaneously, each expressing a different TCR of interest and distinguishable by flow cytometry. Once TCR expression cell lines are made they can be used indefinitely for making new T-cell lines with just one transduction step. This multiplexing system permits screening numbers of TCR-antigen interactions that would otherwise be impractical, can be used in a variety of contexts (i.e., screening individual antigens or antigen pools), and can be applied to study any T-cell-MHC-antigen trimolecular interaction.

In psychiatry, the social zeitgeber theory argues that social life provides important social cues that entrain circadian rhythms. Disturbance of these social cues might lead do dis-entrainment of circadian rhythms and evoke somatic symptoms that increase the risk of mood disorders. In preventing and treating patients with bipolar disorders, the Interpersonal and Social Rhythm Therapy (IPSRT) relies on the Social Rhythm Metric (SRM) to (re)establish patients’ social cues and an re-entrain circadian rhythms. Since the SRM quantifies social rhythms that are derived from a patient’s interaction with a social environment, this contribution (a) calculates the SRM of the social environment of a representative healthy population study (n = 1249), (b) evaluates the robustness of the SRM as a quantifier of social rhythms by matching the scores of the pilot study, revealing the near absence of variance across population characteristics and investigation months—circadian rhythms need to be entrained for every month and for everyone—and (c) examines its use in IPSRT by relating high SRM-scores to lower psychological distress (p = 0.004) and low SRM-scores to higher social and emotional dysfunction (p = 0.018).

Children and adolescents with cancer often participate in medical and psychosocial research throughout their diagnosis and treatment. Furthermore, this involvement frequently extends into the survivorship period. Sometimes referred to as “doubly vulnerable” research participants, children and adolescents with cancer are not only minors, but also minors facing significant medical, developmental, and psychosocial stressors associated with chronic illness. Thus, it is important to exercise care in designing and conducting research with this population; however, these considerations have not been adequately addressed in pediatric healthcare literature. Therefore, the purpose of this review is to describe the research preferences and experiences of children and adolescents with cancer to identify techniques for supporting this population as research participants. By incorporating developmentally appropriate, context-specific, and child-centered adjustments, researchers can help children and adolescents with cancer effectively and meaningfully describe their illness experiences while also developing a positive outlook on future research participation.

During the French Revolution and inspired by the Enlightenment, an attempt was made to replace the Gregorian calendar (which was based on ‘irrational’ overlapping cycles linked to religious celebrations) by the Republican calendar (which was based on ‘rational’ clearly nested cycles in accordance with the metric system). Although the starting point was an ideological and aesthetic expression of rationalism, this calendar also had to fulfill a coordinating and integrating function. Thus the calendric reform faced a tremendous challenge: re-creating a socio-temporal order. One of the crucial socio-temporal frameworks that guide daily behavior in Western societies is the 7-day cycle of the week. In the new calendar, the week was to be replaced by the 10-day cycle or the décade, which turned out the greatest stumbling block for calendar-reformation. Theoretically this is explained by the social nature of time and the ‘second nature’ of time reckoning, but the unawareness of a socially established weekly rhythm in our daily behavior is hard to illustrate. Today, however, society is full of traces of so-called ‘big data’ that humans leave behind. This paper uses ‘big data’ on re-charges of electronic keys to show that even though a 10-day re-charging cycle is proposed, a 7-day re-charging cycle will surface.

Los juegos infantiles constituyen momento de riqueza en interacciones socia‑ les, objeto de interés tanto para descripción de la cultura infantil como de la Psicología de Desarrollo. la presente investigación trata de describir los juegos en las calles de un barrio de la periferia de la ciudad de Belém‑PA, y relacionarlas con la edad y el género de los participantes. Participaron del estudio 668 niños y adolescentes (423 niños 245 niñas), re‑ sidentes o visitantes del área investigada, que se encontraban jugando durante el período de recogida de datos. los instrumentos utilizados fueron: hoja de registro y cuestionario sociodemográfico. la técnica escogida fue la barredura. Fue alta la frecuencia y variancia de juegos, totalizando 17.877 registros, distribuidos en 176 juegos distintos. El perfil del juga‑ dor más observado fue de niños en grupo de edad entre 10‑13 años, siendo juegos de re‑ glas la categoría más frecuente. En general, se destaca la calle como contexto favorecedor de juegos colectivos.