Multiscale Immune Selection and the Transmission-Diversity Feedback in Antigenically Diverse Pathogen Systems

This is the final version of the article. Available from University of Chicago Press via the DOI in this record.Antigenic diversity is commonly used by pathogens to enhance their transmission success. Within-host clonal antigenic variation helps to maintain long infectious periods, whereas high levels of allelic diversity at the population level significantly expand the pool of susceptible individuals. Diversity, however, is not necessarily a static property of a pathogen population but in many cases is generated by the very act of infection and transmission, and it is therefore expected to respond dynamically to changes in transmission and immune selection. We hypothesized that this coupling creates a positive feedback whereby infection and disease transmission promote the generation of diversity, which itself facilitates immune evasion and further infections. To investigate this link in more detail, we considered the human malaria parasite Plasmodium falciparum, one of the most important antigenically diverse pathogens. We developed an individual-based model in which antigenic diversity emerges as a dynamic property from the underlying transmission processes. Our results show that the balance between stochastic extinction and the generation of new antigenic variants is intrinsically linked to within-host and between-host immune selection. This in turn determines the level of diversity that can be maintained in a given population. Furthermore, the transmission-diversity feedback can lead to temporal lags in the response to natural or intervention-induced perturbations in transmission rates. Our results therefore have important implications for monitoring and assessing the effectiveness of disease control efforts

Hybrid Control Systems: a Design Case Study

This paper presents a modification to UML to improve the modelling and analysis of discrete-event dynamic system (DEDS) representations of manufacturing systems. It shows how Petri nets can be used to improve the representation and analysis of the dynamic model of a system specified using UML. Finally the technique is illustrated by its application to a simplified production line

Efficiency of hydrophobic phosphonium ionic liquids and DMSO as recyclable cellulose dissolution and regeneration media

Hydrophobic, long-chain tetraalkylphosphonium acetate salts (ionic liquids) were combined with a dipolar aprotic co-solvent, dimethylsulfoxide (DMSO), and the feasibility of these solvent systems for cellulose dissolution and regeneration was studied. A 60 : 40 w/w mixture of the ionic liquid tetraoctylphosphonium acetate ([P-8888][OAc]) and DMSO was found to dissolve up to 8 wt% cellulose, whilst trioctyl(tetradecyl) phosphonium acetate ([P-14888][OAc]) dissolved up to 3 wt% cellulose. Water (an anti-solvent for cellulose) was found to give rise to biphasic liquid-liquid systems when combined with these mixtures, yielding an upper phase rich in ionic liquid and a lower aqueous phase. The liquid-liquid equilibria of the ternary systems were experimentally determined, finding that DMSO strongly partitioned towards the aqueous phase. Thus, a process scheme involving simultaneous regeneration of cellulose and recycling of the solvent system was envisioned, and demonstrated on a large scale using [P-8888] [OAc]. A large portion of the ionic liquid (ca. 60 wt%) was directly recovered via phase separation, with a further 37 wt% being recovered from the swollen cellulose phase and residual materials, bringing recovery to 97%. XRD analysis of the recovered cellulose materials showed a loss of crystallinity and conversion from Cellulose I to Cellulose II. Non-dissolving compositions of ionic liquid and DMSO did not affect cellulose crystallinity after cellulose pulp treatment.Peer reviewe

Developmental inventories using illiterate parents as informants:Communicative Development Inventory (CDI) adaptation for two Kenyan languages

Communicative Development Inventories (CDIs, parent-completed language development checklists) are a helpful tool to assess language in children who are unused to interaction with unfamiliar adults. Generally, CDIs are completed in written form, but in developing country settings parents may have insufficient literacy to complete them alone. We designed CDIs to assess language development in children aged 0;8 to 2;4 in two languages used in Coastal communities in Kenya. Measures of vocabulary, gestures, and grammatical constructions were developed using both interviews with parents from varying backgrounds, and vocabulary as well as grammatical constructions from recordings of children's spontaneous speech. The CDIs were then administered in interview format to over 300 families. Reliability and validity ranged from acceptable to excellent, supporting the use of CDIs when direct language testing is impractical, even when children have multiple caregivers and where respondents have low literacy levels

Impact of social prescribing to address loneliness: a mixed methods evaluation of a national social prescribing programme

Loneliness is considered a global public health issue because of its detrimental impact on physical and mental health but little is known about which interventions can reduce loneliness. One potential intervention is social prescribing, where a link worker helps service‐users to access appropriate support such as community activities and social groups. Some qualitative studies have identified that social prescribing may help to reduce service‐users’ loneliness. Given this, the British Red Cross (a third sector organisation) developed and delivered a national social prescribing service in the United Kingdom to support people who were experiencing, or at risk of, loneliness. Service‐users could receive up to 12 weeks of support from a link worker. A mixed methods study was conducted to understand the impact of the support on loneliness, and to identify the facilitators and barriers to service delivery. The study included: (a) analysis of quantitative data collected routinely between May 2017 and December 2019 (n = 10,643) including pre‐post analysis of UCLA data (n = 2,250) and matched comparator work to measure changes in loneliness; (b) semi‐structured interviews with service‐users, link workers and volunteers (n = 60) and (c) a Social Return on Investment Analysis. The majority of the service‐users (72.6%, n = 1634/2250) felt less lonely after receiving support. The mean change in UCLA score was −1.84 (95% CI −1.91 to −1.77) of a maximum change of 6.00 (decrease indicates an improvement). Additional benefits included improved wellbeing, increased confidence and life having more purpose. The base case analysis estimated a social return on investment of £3.42 per £1 invested in the service. Having skilled link workers and support tailored to individual needs appeared key. However, challenges included utilising volunteers, meeting some service‐users’ needs in relation to signposting and sustaining improvements in loneliness. Nonetheless, the service appeared successful in supporting service‐users experiencing loneliness

Service users’ perspectives of a national social prescribing programme to address loneliness and social Isolation: a qualitative study

Loneliness is considered to be a global public health challenge, impacting a range of physical and mental health conditions. Social prescribing, whereby service users are signposted into community-based activities and social groups by a community link worker, has been suggested as one mechanism to reduce service users’ loneliness and social isolation. This paper reflects on service users’ experiences of accessing a national social prescribing scheme. Drawing on qualitative findings from interviews with service users who were receiving support through a social prescribing programme between October 2017 and December 2018 (n = 26, with n = 12 interviewed a second time), we reflect on their experiences of the programme. We consider some of the complexities of providing short-term support with a focus on signposting people into local activities, when many service users prefer the companionship of their link worker. Furthermore, we highlight some of the difficulties in ending short-term support. Crucially, we highlight the importance of considering the intersection of the social determinants of health. We suggest that social prescribing schemes may exacerbate inequalities if consideration is not given to the ways in which people are (dis)advantaged in accessing the social capital necessary for their initial and continued involvement

Evaluation of the British Red Cross community connectors programme : final report, Social Return on Investment : May 2019

Background: A Social Return on Investment (SROI) was undertaken to evaluate the economic impact of the British Red Cross Community Connectors programme. The programme was a form of social prescribing, which was focused on alleviating loneliness. This type of analysis is particularly suited to interventions that include a wide range of benefits (Nicholls, Lawlor, Neitzert, & Goodspeed, 2009). Objectives: The SROI sought to address the following objectives. • Provide robust evidence to inform the British Red Cross decision making with regard to wider rollout and support advocacy • Understand the costs of service delivery and make judgments about its value of outcomes including reductions in the use of other services that might occur as a consequence of the support provided to service users Methods: The different benefits and costs included were informed by the literature and decided by stakeholders and local experts, using workshops, surveys and informal conversations. This approach promotes relevance of findings and encourages a collaborative focus. The SROI approach has been successfully used to evaluate wellbeing interventions. For example, a community befriending programme (Arvidson, Battye, & Salisbury, 2014). It is widely used and recognised by decision makers; for example, the Cabinet Office has issued guidance on how to use SROI. A key advantage of the SROI for evaluating the Community Connectors project is that it enables the economics model to develop over time, and be shaped by unanticipated cost and benefits. This enables any changes to the programme or its costs/benefits to be incorporated. This is important because of the innovative and developing nature of the Community Connectors programme. Findings: The Inputs taken into account (costs for delivering the project) are British Red Cross central organisational costs for the set-up and coordination of the project, British Red Cross project delivery costs and the time donated by volunteers for their training and participation in the Community Connector service. The outcomes (benefits) that are taken into account are improved wellbeing of volunteer, improved wellbeing of service-users (using SWEMWBS scores) and reduced missed health appointments. Wellbeing is valued using the wellbeing valuation approach (Fujiwara, 2013). Conclusion: The ultimate findings from these calculations included total inputs, outcomes, net present value and Social Return on Investment ratio. This demonstrates an economic return to society in general of £1.48 for each pound invested in the project. A range of sensitivity analyses were also conducted

The Unique Seed Protein Composition of Quality Protein Popcorn Promotes Growth of Beneficial Bacteria From the Human Gut Microbiome

The effects of fiber, complex carbohydrates, lipids, and small molecules from food matrices on the human gut microbiome have been increasingly studied. Much less is known about how dietary protein can influence the composition and function of the gut microbial community. Here, we used near-isogenic maize lines of conventional popcorn and quality-protein popcorn (QPP) to study the effects of the opaque-2 mutation and associated quality-protein modifiers on the human gut microbiome. Opaque-2 blocks the synthesis of major maize seed proteins (α-zeins), resulting in a compensatory synthesis of new seed proteins that are nutritionally beneficial with substantially higher levels of the essential amino acids lysine and tryptophan. We show that QPP lines stimulate greater amounts of butyrate production by human gut microbiomes in in vitro fermentation of popped and digested corn from parental and QPP hybrids. In human gut microbiomes derived from diverse individuals, bacterial taxa belonging to the butyrate-producing family Lachnospiraceae, including the genera Coprococcus and Roseburia were consistently increased when fermenting QPP vs. parental popcorn lines. We conducted molecular complementation to further demonstrate that lysine-enriched seed protein can stimulate growth and butyrate production by microbes through distinct pathways. Our data show that organisms such as Coprococcus can utilize lysine and that other gut microbes, such as Roseburia spp., instead, utilize fructoselysine produced during thermal processing (popping) of popcorn. Thus, the combination of seed composition in QPP and interaction of protein adducts with carbohydrates during thermal processing can stimulate the growth of health-promoting, butyrate-producing organisms in the human gut microbiome through multiple pathways

The effect of sleep deprivation on objective and subjective measures of facial appearance

This study was funded by the Swedish Research Council, FORTE (Swedish Research Council for Health, Working Life and Welfare), and The Swedish Foundation for Humanities and Social Sciences.The faces of people who are sleep deprived are perceived by others as looking paler, less healthy and less attractive compared to when well rested. However, there is little research using objective measures to investigate sleep‐loss‐related changes in facial appearance. We aimed to assess the effects of sleep deprivation on skin colour, eye openness, mouth curvature and periorbital darkness using objective measures, as well as to replicate previous findings for subjective ratings. We also investigated the extent to which these facial features predicted ratings of fatigue by others and could be used to classify the sleep condition of the person. Subjects (n = 181) were randomised to one night of total sleep deprivation or a night of normal sleep (8–9 hr in bed). The following day facial photographs were taken and, in a subset (n = 141), skin colour was measured using spectrophotometry. A separate set of participants (n = 63) later rated the photographs in terms of health, paleness and fatigue. The photographs were also digitally analysed with respect to eye openness, mouth curvature and periorbital darkness. The results showed that neither sleep deprivation nor the subjects’ sleepiness was related to differences in any facial variable. Similarly, there was no difference in subjective ratings between the groups. Decreased skin yellowness, less eye openness, downward mouth curvature and periorbital darkness all predicted increased fatigue ratings by others. However, the combination of appearance variables could not be accurately used to classify sleep condition. These findings have implications for both face‐to‐face and computerised visual assessment of sleep loss and fatigue.PostprintPeer reviewe