Vaccination with a Human Papillomavirus L2 Multimer Provides Broad Protection against 17 Human Papillomavirus Types in the Mouse Cervicovaginal Challenge Model.

Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11-88) from five human alphapapillomavirus genotypes in E. coli under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard in vitro and in vivo toxicology studies suggest a promising safety profile. These findings suggest LBTA's promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).

Understanding the Role of Imide-Based Salts and Borate-Based Additives for Safe and High-Performance Glyoxal-Based Electrolytes in Ni-Rich NMC811 Cathodes for Li-Ion Batteries.

Herein, the design of novel and safe electrolyte formulations for high-voltage Ni-rich cathodes is reported. The solvent mixture comprising 1,1,2,2-tetraethoxyethane and propylene carbonate not only displays good transport properties, but also greatly enhances the overall safety of the cell thanks to its low flammability. The influence of the conducting salts, that is, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium bis(fluorosulfonyl)imide (LiFSI), and of the additives lithium bis(oxalato)borate (LiBOB) and lithium difluoro(oxalato)borate (LiDFOB) is examined. Molecular dynamics simulations are carried out to gain insights into the local structure of the different electrolytes and the lithium-ion coordination. Furthermore, special emphasis is placed on the film-forming abilities of the salts to suppress the anodic dissolution of the aluminum  current collector and to create a stable cathode electrolyte interphase (CEI). In this regard, the borate-based additives significantly alleviate the intrinsic challenges associated with the use of LiTFSI and LiFSI salts. It is worth remarking that a superior cathode performance is achieved by using the LiFSI/LiDFOB electrolyte, displaying a high specific capacity of 164 mAh g-1 at 6 C and ca. 95% capacity retention after 100 cycles at 1 C. This is attributed to the rich chemistry of the generated CEI layer, as confirmed by ex situ X-ray photoelectron spectroscopy.

Aerosol Inhalation of Chimpanzee Adenovirus Vectors (ChAd68) Expressing Ancestral or Omicron BA.1 Stabilized Pre-Fusion Spike Glycoproteins Protects Non-Human Primates against SARS-CoV-2 Infection.

Current COVID-19 vaccines are effective countermeasures to control the SARS-CoV-2 virus pandemic by inducing systemic immune responses through intramuscular injection. However, respiratory mucosal immunization will be needed to elicit local sterilizing immunity to prevent virus replication in the nasopharynx, shedding, and transmission. In this study, we first compared the immunoprotective ability of a chimpanzee replication-deficient adenovirus-vectored COVID-19 vaccine expressing a stabilized pre-fusion spike glycoprotein from the ancestral SARS-CoV-2 strain Wuhan-Hu-1 (BV-AdCoV-1) administered through either aerosol inhalation, intranasal spray, or intramuscular injection in cynomolgus monkeys and rhesus macaques. Compared with intranasal administration, aerosol inhalation of BV-AdCoV-1 elicited stronger humoral and mucosal immunity that conferred excellent protection against SARS-CoV-2 infection in rhesus macaques. Importantly, aerosol inhalation induced immunity comparable to that obtained by intramuscular injection, although at a significantly lower dose. Furthermore, to address the problem of immune escape variants, we evaluated the merits of heterologous boosting with an adenovirus-based Omicron BA.1 vaccine (C68-COA04). Boosting rhesus macaques vaccinated with two doses of BV-AdCoV-1 with either the homologous or the heterologous C68-COA04 vector resulted in cross-neutralizing immunity against WT, Delta, and Omicron subvariants, including BA.4/5 stronger than that obtained by administering a bivalent BV-AdCoV-1/C68-COA04 vaccine. These results demonstrate that the administration of BV-AdCoV-1 or C68-COA04 via aerosol inhalation is a promising approach to prevent SARS-CoV-2 infection and transmission and curtail the pandemic spread.

SNapp, a Tailored Smartphone App Intervention to Promote Walking in Adults of Low Socioeconomic Position: Development and Qualitative Pilot Study.

BACKGROUND: Adults of low socioeconomic position (SEP) are generally less physically active than those who are more socioeconomically advantaged, which increases their cardiovascular disease incidence risk. Moreover, individuals of low SEP are often less easily reached with physical activity (PA) interventions than individuals of higher SEP. Smartphone apps have been presented as a promising platform for delivering PA interventions to difficult-to-reach individuals of low SEP. Although PA apps are widely available, they are rarely based on health behavior theories and most predominantly offer generic PA advice. Consequently, it is unlikely that available apps are the most effective PA intervention tools. OBJECTIVE: To respond to these areas for improvement, we developed SNapp, an app-based intervention encouraging adults of low SEP to increase PA by providing tailored coaching messages targeting walking behavior. This study aimed to describe SNapp's stepwise development and pilot evaluation process. METHODS: We applied a stepwise approach: analyzing the health problem, developing a program framework, developing tailoring assessments, writing tailored messages, automating the tailoring process, and implementing and evaluating the program in a qualitative pilot study (11 participants). RESULTS: SNapp consisted of several elements. First, an app was developed to collect step count and geolocation data using smartphone sensor functionalities. In addition, a survey measure was created to assess users' behavior change technique (BCT) preferences. These 3 data types were used to tailor SNapp's coaching messages to stimulate walking. This allows SNapp to offer feedback on performance levels, contextually tailored prompts when users are near green spaces, and coaching content that aligns with individual BCT preferences. Finally, a server-based Python program that interacts with databases containing user data and tailored messages was built using Microsoft Azure to select and automatically send messages to users through Telegram messenger. Pilot study findings indicated that SNapp was rated positively, with participants reporting that its design, technical functioning, and message content were acceptable. Participants suggested additional functionalities that are worth considering for future updates. CONCLUSIONS: SNapp is an app-based intervention that aims to promote walking in adults of low SEP by offering tailored coaching messages. Its development is theory based, and it is among the first to incorporate contextualized feedback and content tailored to individual BCT preferences. The effectiveness of SNapp will be evaluated in a 12-month real-life parallel cluster-randomized controlled trial.

Intranasal delivery of a chimpanzee adenovirus vector expressing a pre-fusion spike (BV-AdCoV-1) protects golden Syrian hamsters against SARS-CoV-2 infection.

We evaluated the immunogenicity and protective ability of a chimpanzee replication-deficient adenovirus vectored COVID-19 vaccine (BV-AdCoV-1) expressing a stabilized pre-fusion SARS-CoV-2 spike glycoprotein in golden Syrian hamsters. Intranasal administration of BV-AdCoV-1 elicited strong humoral and cellular immunity in the animals. Furthermore, vaccination prevented weight loss, reduced SARS-CoV-2 infectious virus titers in the lungs as well as lung pathology and provided protection against SARS-CoV-2 live challenge. In addition, there was no vaccine-induced enhanced disease nor immunopathological exacerbation in BV-AdCoV-1-vaccinated animals. Furthermore, the vaccine induced cross-neutralizing antibody responses against the ancestral strain and the B.1.617.2, Omicron(BA.1), Omicron(BA.2.75) and Omicron(BA.4/5) variants of concern. These results demonstrate that BV-AdCoV-1 is potentially a promising candidate vaccine to prevent SARS-CoV-2 infection, and to curtail pandemic spread in humans.

Understanding the complexities of Bluetooth for representing real-life social networks: A methodology for inferring and validating Bluetooth-based social network graphs.

Bluetooth (BT) data has been extensively used for recognizing social patterns and inferring social networks, as BT is widely present in everyday technological devices. However, even though collecting BT data is subject to random noise and may result in substantial measurement errors, there is an absence of rigorous procedures for validating the quality of the inferred BT social networks. This paper presents a methodology for inferring and validating BT-based social networks based on parameter optimization algorithm and social network analysis (SNA). The algorithm performs edge inference in a brute-force search over a given BT data set, for deriving optimal BT social networks by validating them with predefined ground truth (GT) networks. The algorithm seeks to optimize a set of parameters, predefined considering some reliability challenges associated to the BT technology itself. The outcomes show that optimizing the parameters can reduce the number of BT data false positives or generate BT networks with the minimum amount of BT data observations. The subsequent SNA shows that the inferred BT social networks are unable to reproduce some network characteristics present in the corresponding GT networks. Finally, the generalizability of the proposed methodology is demonstrated by applying the algorithm on external BT data sets, while obtaining comparable results.

Reducing cardiometabolic risk in adults with a low socioeconomic position: protocol of the Supreme Nudge parallel cluster-randomised controlled supermarket trial.

BACKGROUND: Unhealthy lifestyle behaviours such as unhealthy dietary intake and insufficient physical activity (PA) tend to cluster in adults with a low socioeconomic position (SEP), putting them at high cardiometabolic disease risk. Educational approaches aiming to improve lifestyle behaviours show limited effect in this population. Using environmental and context-specific interventions may create opportunities for sustainable behaviour change. In this study protocol, we describe the design of a real-life supermarket trial combining nudging, pricing and a mobile PA app with the aim to improve lifestyle behaviours and lower cardiometabolic disease risk in adults with a low SEP. METHODS: The Supreme Nudge trial includes nudging and pricing strategies cluster-randomised on the supermarket level, with: i) control group receiving no intervention; ii) group 1 receiving healthy food nudges (e.g., product placement or promotion); iii) group 2 receiving nudges and pricing strategies (taxing of unhealthy foods and subsidizing healthy foods). In collaboration with a Dutch supermarket chain we will select nine stores located in low SEP neighbourhoods, with the nearest competitor store at > 1 km distance and managed by a committed store manager. Across the clusters, a personalized mobile coaching app targeting walking behaviour will be randomised at the individual level, with: i) control group; ii) a group receiving the mobile PA app. All participants (target n = 1485) should be Dutch-speaking, aged 45-75 years with a low SEP and purchase more than half of their household grocery shopping at the selected supermarkets. Participants will be recruited via advertisements and mail-invitations followed by community-outreach methods. Primary outcomes are changes in systolic blood pressure, LDL-cholesterol, HbA1c and dietary intake after 12 months follow-up. Secondary outcomes are changes in diastolic blood pressure, blood lipid markers, waist circumference, steps per day, and behavioural factors including healthy food purchasing, food decision style, social cognitive factors related to nudges and to walking behaviours and customer satisfaction after 12 months follow-up. The trial will be reflexively monitored to support current and future implementation. DISCUSSION: The findings can guide future research and public health policies on reducing lifestyle-related health inequalities, and contribute to a supermarket-based health promotion intervention implementation roadmap. TRIAL REGISTRATION: Dutch Trial Register ID NL7064, 30th of May, 2018.

The Use and Effects of an App-Based Physical Activity Intervention "Active2Gether" in Young Adults: Quasi-Experimental Trial.

BACKGROUND: Insufficient physical activity (PA) is highly prevalent and associated with adverse health conditions and the risk of noncommunicable diseases. To increase levels of PA, effective interventions to promote PA are needed. Present-day technologies such as smartphones, smartphone apps, and activity trackers offer several possibilities in health promotion. OBJECTIVE: This study aimed to explore the use and short-term effects of an app-based intervention (Active2Gether) to increase the levels of PA in young adults. METHODS: Young adults aged 18-30 years were recruited (N=104) using diverse recruitment strategies. The participants were allocated to the Active2Gether-Full condition (tailored coaching messages, self-monitoring, and social comparison), Active2Gether-Light condition (self-monitoring and social comparison), and the Fitbit-only control condition (self-monitoring). All participants received a Fitbit One activity tracker, which could be synchronized with the intervention apps, to monitor PA behavior. A 12-week quasi-experimental trial was conducted to explore the intervention effects on weekly moderate-to-vigorous PA (MVPA) and relevant behavioral determinants (ie, self-efficacy, outcome expectations, social norm, intentions, satisfaction, perceived barriers, and long-term goals). The ActiGraph wGT3XBT and GT3X+ were used to assess baseline and postintervention follow-up PA. RESULTS: Compared with the Fitbit condition, the Active2Gether-Light condition showed larger effect sizes for minutes of MVPA per day (regression coefficient B=3.1; 95% CI -6.7 to 12.9), and comparatively smaller effect sizes were seen for the Active2Gether-Full condition (B=1.2; 95% CI -8.7 to 11.1). Linear and logistic regression analyses for the intervention effects on the behavioral determinants at postintervention follow-up showed no significant intervention effects of the Active2Gether-Full and Active2Gether-Light conditions. The overall engagement with the Fitbit activity tracker was high (median 88% (74/84) of the days), but lower in the Fitbit condition. Participants in the Active2Gether conditions reported more technical problems than those in the Fitbit condition. CONCLUSIONS: This study showed no statistically significant differences in MVPA or determinants of MVPA after exposure to the Active2Gether-Full condition compared with the Active2Gether-Light or Fitbit condition. This might partly be explained by the small sample size and the low rates of satisfaction in the participants in the two Active2Gether conditions that might be because of the high rates of technical problems.

Effectiveness and cost-effectiveness of personalised dietary advice aiming at increasing protein intake on physical functioning in community-dwelling older adults with lower habitual protein intake: rationale and design of the PROMISS randomised controlled trial.

INTRODUCTION: Short-term metabolic and observational studies suggest that protein intake above the recommended dietary allowance of 0.83 g/kg body weight (BW)/day may support preservation of lean body mass and physical function in old age, but evidence from randomised controlled trials is inconclusive. METHODS AND ANALYSIS: The PRevention Of Malnutrition In Senior Subjects in the EU (PROMISS) trial examines the effect of personalised dietary advice aiming at increasing protein intake with or without advice regarding timing of protein intake to close proximity of usual physical activity, on change in physical functioning after 6 months among community-dwelling older adults (≥65 years) with a habitual protein intake of <1.0 g/kg adjusted (a)BW/day. Participants (n=264) will be recruited in Finland and the Netherlands, and will be randomised into three groups; two intervention groups and one control group. Intervention group 1 (n=88) receives personalised dietary advice and protein-enriched food products in order to increase their protein intake to at least 1.2 g/kg aBW/day. Intervention group 2 (n=88) receives the same advice as described for intervention group 1, and in addition advice to consume 7.5-10 g protein through protein-(en)rich(ed) foods within half an hour after performing usual physical activity. The control group (n=88) receives no intervention. All participants will be invited to attend lectures not related to health. The primary outcome is a 6-month change in physical functioning measured by change in walk time using a 400 m walk test. Secondary outcomes are: 6-month change in the Short Physical Performance Battery score, muscle strength, body composition, self-reported mobility limitations, quality of life, incidence of frailty, incidence of sarcopenia risk and incidence of malnutrition. We also investigate cost-effectiveness by change in healthcare costs. DISCUSSION: The PROMISS trial will provide evidence whether increasing protein intake, and additionally optimising the timing of protein intake, has a positive effect on the course of physical functioning after 6 months among community-dwelling older adults with a habitual protein intake of <1.0 g/kg aBW/day. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the Helsinki University Central Hospital, Finland (ID of the approval: HUS/1530/2018) and The Medical Ethical Committee of the Amsterdam UMC, location VUmc, Amsterdam, the Netherlands (ID of the approval: 2018.399). All participants provided written informed consent prior to being enrolled onto the study. Results will be submitted for publication in peer-reviewed journals and will be made available to stakeholders (ie, older adults, healthcare professionals and industry). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03712306).

Digital Health Behavior Change Technology: Bibliometric and Scoping Review of Two Decades of Research.

BACKGROUND: Research on digital technology to change health behavior has increased enormously in recent decades. Due to the interdisciplinary nature of this topic, knowledge and technologies from different research areas are required. Up to now, it is not clear how the knowledge from those fields is combined in actual applications. A comprehensive analysis that systematically maps and explores the use of knowledge within this emerging interdisciplinary field is required. OBJECTIVE: This study aims to provide an overview of the research area around the design and development of digital technologies for health behavior change and to explore trends and patterns. METHODS: A bibliometric analysis is used to provide an overview of the field, and a scoping review is presented to identify the trends and possible gaps. The study is based on the publications related to persuasive technologies and health behavior change in the last 18 years, as indexed by the Web of Science and Scopus (317 and 314 articles, respectively). In the first part, regional and time-based publishing trends; research fields and keyword co-occurrence networks; influential journals; and collaboration network between influential authors, countries, and institutions are examined. In the second part, the behavioral domains, technological means and theoretical foundations are investigated via a scoping review. RESULTS: The literature reviewed shows a clear and emerging trend after 2001 in technology-based behavior change, which grew exponentially after the introduction of the smartphone around 2009. Authors from the United States, Europe, and Australia have the highest number of publications in the field. The three most active research areas are computer science, public and occupational health, and psychology. The keyword "mhealth" was the dominant term and predominantly used together with the term "physical activity" and "ehealth". A total of three strong clusters of coauthors have been found. Nearly half of the total reported papers were published in three journals. The United States, the United Kingdom, and the Netherlands have the highest degree of author collaboration and a strong institutional network. Mobile phones were most often used as a technology platform, regardless of the targeted behavioral domain. Physical activity and healthy eating were the most frequently targeted behavioral domains. Most articles did not report about the behavior change techniques that were applied. Among the reported behavior change techniques, goal setting and self-management were the most frequently reported. CONCLUSIONS: Closer cooperation and interaction between behavioral sciences and technological areas is needed, so that theoretical knowledge and new technological advancements are better connected in actual applications. Eventually, this could result in a larger societal impact, an increase of the effectiveness of digital technologies for health behavioral change, and more insight in the relationship between behavioral change strategies and persuasive technologies' effectiveness.

Identifying Influence Agents That Promote Physical Activity Through the Simulation of Social Network Interventions: Agent-Based Modeling Study.

BACKGROUND: Social network interventions targeted at children and adolescents can have a substantial effect on their health behaviors, including physical activity. However, designing successful social network interventions is a considerable research challenge. In this study, we rely on social network analysis and agent-based simulations to better understand and capitalize on the complex interplay of social networks and health behaviors. More specifically, we investigate criteria for selecting influence agents that can be expected to produce the most successful social network health interventions. OBJECTIVE: The aim of this study was to test which selection criterion to determine influence agents in a social network intervention resulted in the biggest increase in physical activity in the social network. To test the differences among the selection criteria, a computational model was used to simulate different social network interventions and observe the intervention's effect on the physical activity of primary and secondary school children within their school classes. As a next step, this study relied on the outcomes of the simulated interventions to investigate whether social network interventions are more effective in some classes than others based on network characteristics. METHODS: We used a previously validated agent-based model to understand how physical activity spreads in social networks and who was influencing the spread of behavior. From the observed data of 460 participants collected in 26 school classes, we simulated multiple social network interventions with different selection criteria for the influence agents (ie, in-degree centrality, betweenness centrality, closeness centrality, and random influence agents) and a control condition (ie, no intervention). Subsequently, we investigated whether the detected variation of an intervention's success within school classes could be explained by structural characteristics of the social networks (ie, network density and network centralization). RESULTS: The 1-year simulations showed that social network interventions were more effective compared with the control condition (beta=.30; t100=3.23; P=.001). In addition, the social network interventions that used a measure of centrality to select influence agents outperformed the random influence agent intervention (beta=.46; t100=3.86; P<.001). Also, the closeness centrality condition outperformed the betweenness centrality condition (beta=.59; t100=2.02; P=.046). The anticipated interaction effects of the network characteristics were not observed. CONCLUSIONS: Social network intervention can be considered as a viable and promising intervention method to promote physical activity. We demonstrated the usefulness of applying social network analysis and agent-based modeling as part of the social network interventions' design process. We emphasize the importance of selecting the most successful influence agents and provide a better understanding of the role of network characteristics on the effectiveness of social network interventions.

App-Based Intervention Combining Evidence-Based Behavior Change Techniques With a Model-Based Reasoning System to Promote Physical Activity Among Young Adults (Active2Gether): Descriptive Study of the Development and Content.

BACKGROUND: The Active2Gether intervention is an app-based intervention designed to help and encourage young adults to become and remain physically active by means of personalized, real-time activity tracking and context-specific feedback. OBJECTIVE: The objective of our study was to describe the development and content of the Active2Gether intervention for physical activity promotion. METHODS: A systematic and stepwise approach was used to develop the Active2Gether intervention. This included formulating objectives and a theoretical framework, selecting behavior change techniques, specifying the tailoring, pilot testing, and describing an evaluation protocol. RESULTS: The development of the Active2Gether intervention comprised seven steps: analyzing the (health) problem, developing a program framework, writing (tailored) messages, developing tailoring assessments, developing the Active2Gether intervention, pilot testing, and testing and evaluating the intervention. The primary objective of the intervention was to increase the total time spent in moderate-vigorous physical activity for those who do not meet the Dutch guideline, maintain physical activity levels of those who meet the guideline, or further increase physical activity levels if they so indicated. The theoretical framework is informed by the social cognitive theory, and insights from other theories and evidence were added for specific topics. Development of the intervention content and communication channel resulted in the development of an app that provides highly tailored coaching messages that are framed in an autonomy-supportive style. These coaching messages include behavior change techniques aiming to address relevant behavioral determinants (eg, self-efficacy and outcome expectations) and are partly context specific. A model-based reasoning engine has been developed to tailor the intervention with respect to the type of support provided by the app, send relevant and context-specific messages to the user, and tailor the graphs displayed in the app. For the input of the tailoring, different instruments and sensors are used, such as an activity monitor (Fitbit One), Web-based and mobile questionnaires, and the location services on the user's mobile phone. CONCLUSIONS: The systematic and stepwise approach resulted in an intervention that is based on theory and input from end users. The use of a model-based reasoning system to provide context-specific coaching messages goes beyond many existing eHealth and mHealth interventions.

Improving cardiometabolic health through nudging dietary behaviours and physical activity in low SES adults: design of the Supreme Nudge project.

BACKGROUND: Initiating and maintaining a healthy lifestyle -including healthy eating and sufficient physical activity- is key for cardiometabolic health. A health-promoting environment can facilitate a healthy lifestyle, and may be especially helpful to reach individuals with a lower socio-economic status (SES). In the Supreme Nudge project, we will study the effects of pricing and nudging strategies in the supermarket - one of the most important point-of-choice settings for food choices - and of a context-specific mobile physical activity promotion app. This paper describes the stepwise and theory-based design of Supreme Nudge, which aims to develop, implement and evaluate environmental changes for a sustained impact on lifestyle behaviours and cardiometabolic health in low SES adults. METHODS: Supreme Nudge uses a multi-disciplinary and mixed methods approach, integrating participatory action research, qualitative interviews, experimental pilot studies, and a randomized controlled trial in a real-life (supermarket) setting. First, we will identify the needs, characteristics and preferences of the target group as well as of the participating supermarket chain. Second, we will conduct a series of pilot studies to test novel, promising and feasible intervention components. Third, a final selection of intervention components will be implemented in a full-scale randomised controlled supermarket trial. Approximately 1000 low SES adults will be recruited across 8-12 supermarkets and randomised at supermarket level to receive 1) no intervention (control); 2) environmental nudges such as food product placement or promotion; 3) nudges and a tailored physical activity app that provides time- and context specific feedback; 4) pricing interventions, nudges, and the physical activity app. The effects on dietary behaviours and physical activity will be evaluated at 3, 6 and 12 months, and on cardiometabolic health at 6 and 12 months. Finally, we will evaluate the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) of the intervention, and we will use insights from System Innovation and Transition Management theories to define the best strategies for implementation and upscaling beyond the study period. DISCUSSION: The Supreme Nudge project is likely to generate thorough evidence relevant for policy and practice on the effects of a mixed method and multi-disciplinary intervention targeting dietary behaviours and physical activity. TRIAL REGISTRATION: The real-life trial has been registered on 30 May 2018, NTR7302 .

Active2Gether: A Personalized m-Health Intervention to Encourage Physical Activity.

Lack of physical activity is an increasingly important health risk. Modern mobile technology, such as smartphones and digital measurement devices, provides new opportunities to tackle physical inactivity. This paper describes the design of a system that aims to encourage young adults to be more physically active. The system monitors the user's behavior, uses social comparison and provides tailored and personalized feedback based on intelligent reasoning mechanisms. As the name suggests, social processes play an important role in the Active2Gether system. The design choices and functioning of the system are described in detail. Based on the experiences with the development and deployment of the system, a number of lessons learnt are provided and suggestions are proposed for improvements in future developments.

ULTEMAT: A mobile framework for smart ecological momentary assessments and interventions.

In this paper we introduce a new Android library, called ULTEMAT, for the delivery of ecological momentary assessments (EMAs) on mobile devices and we present its use in the MoodBuster app developed in the H2020 E-COMPARED project. We discuss context-aware, or event-based, triggers for the presentation of EMAs and discuss the potential they have to improve the effectiveness of mobile provision of mental health interventions as they allow for the delivery of assessments to the patients when and where these are most appropriate. Following this, we present the abilities of ULTEMAT to use such context-aware triggers to schedule EMAs and we discuss how a similar approach can be used for Ecological Momentary Interventions (EMIs).

Is a multivalent hand, foot, and mouth disease vaccine feasible?

Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed.

EV71 vaccines: a first step towards multivalent hand, foot and mouth disease vaccines.

Enterovirus A infections are the primary cause of hand, foot and mouth disease in infants and young children. Enterovirus 71 (EV71) and coxsackievirus A16 have emerged as neurotropic viruses responsible for severe neurological complications and a serious public health threat across the Asia-Pacific region. Formalin-inactivated EV71 vaccines have elicited protection against EV71 but not against coxsackievirus A16 infections. The development of a bivalent formalin-inactivated EV71/FI coxsackievirus A16 vaccine should be the next step towards that of multivalent hand, foot and mouth disease vaccines which should ultimately include other prevalent pathogenic coxsackieviruses and echovirus 30. This editorial summarizes the major challenges faced by the development of hand, foot and mouth disease vaccines.

Review of enterovirus 71 vaccines.

Enterovirus 71 (EV71) and coxsackieviruses are the major causative agents of hand, foot, and mouth disease (HFMD) outbreaks worldwide and have a significant socioeconomic impact, particularly in Asia. Formalin-inactivated (FI) EV71 vaccines evaluated in human clinical trials in China, Taiwan, and Singapore were found to be safe and to elicit strong neutralizing antibody responses against EV71 currently circulating in Asia. The results from 3 different phase 3 clinical trials performed in young children (6-60 months) indicate that the efficacy of FI-EV71 vaccines is >90% against EV71-related HFMDs and >80% against EV71-associated serious diseases, but the vaccines did not protect against coxsackievirus A16 infections. Here we discuss the critical factors affecting EV71 vaccine product registration, including clinical epidemiology, antigenic shift issues in cross-protection and vaccine strain selection, standardized animal models for potency testing, and cost-effective manufacturing processes for potential incorporation of FI-EV71 vaccine into Expanded Programme on Immunization vaccines.

Prospect and challenges for the development of multivalent vaccines against hand, foot and mouth diseases.

Enterovirus 71 (EV71), an emerging neurotropic virus and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth diseases (HFMD). These viruses have become a serious public health threat in the Asia Pacific region. Formalin-inactivated EV71 (FI-EV71) vaccines have been developed, evaluated in human clinical trials and were found to elicit full protection against EV71. Their failure to prevent CVA16 infections could compromise the acceptability of monovalent EV71 vaccines. Bivalent FI-EV71/FI-CVA16 vaccines have been found to elicit strong neutralizing antibody responses against both viruses in animal models but did not protect against CVA6 and CVA10 viral infections in cell culture neutralization assay. In this review, we discuss the critical bottlenecks in the development of multivalent HFMD vaccines, including the selection of vaccine strains, animal models to assess vaccine potency, the definition of end-points for efficacy trials, and the need for improved manufacturing processes to produce affordable vaccines.