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Background: It is reported that the longer-term outcomes for stroke survivors are poor, with a range of unmet needs identified. Objectives: The aims were to develop and test a longer-term stroke care strategy focused on improving the quality of life of stroke survivors and their carers by addressing unmet needs, and maintenance and enhancement of participation (i.e. involvement in life situations). Design: Five overlapping workstreams were undertaken – (1) refinement of content by semistructured interviews with stroke survivors and their carers and by a review of the literature to inform content and delivery of the care strategy; (2) exploration of service models by national survey and focus groups with purposely selected services; (3) intervention development by interaction with a reference group of stroke survivors, carers, and health and social care professionals; (4) refinement and pilot implementation of the developed intervention in three stroke services (case studies); and (5) a cluster randomised controlled feasibility trial in 10 stroke services across England and Wales. Setting: The intervention development work and feasibility trial were in stroke services (inclusive of primary, secondary, community and social care provision) across England and Wales. Participants: Participants were stroke survivors resident in the community and their carers, and health and social care professionals in the included stroke services. Data sources: Interviews with 28 stroke survivors and their carers at least 9 months post stroke ascertained their needs and the barriers to and facilitators of addressing those needs. Additional literature reviews identified 23 needs. No evidence-based interventions to address these needs were reported; self-management was highlighted as a possible delivery mechanism. In workstream 2, a national survey revealed that the most common model of stroke service provision was care up to 12 months post stroke, reported by 46 (40%) services. Thirty-five (30%) services provided care up to 6 months post stroke and 35 (30%) provided care beyond 12 months, thus identifying 6 months post stroke as an appropriate delivery point for a new intervention. Through focus groups in a range of services, stroke survivors’ perceived unmet needs and the barriers to and enablers of service provision were identified. Intervention: Using information obtained in workstreams 1 and 2 and working closely with a stakeholder reference group, we developed an intervention based on the unmet needs prioritised by stroke survivors and their carers (workstream 3). In workstream 4, action groups (clinicians, stroke survivors and researchers) were established in three stroke services that led implementation in their service and contributed to the iterative refinement of the intervention, associated training programme and implementation materials. The intervention (called New Start) was delivered at 6 months post stroke. Key components were problem-solving self-management with survivors and carers, help with obtaining usable information, and helping survivors and their carers build sustainable, flexible support networks. Results: A cluster randomised feasibility trial (workstream 5) was successfully implemented in 10 stroke services across England and Wales, with associated process and health economic evaluations. Five services were randomised to provide New Start, while five continued with usual care; 269 participants were recruited. Progression criteria – in terms of our pre-determined (red, amber, green) criteria for progress to a full trial: target stroke survivor recruitment rates were achieved, on average, across sites (24.1 per site over 6 months, green); 216 (80.3%) registered stroke survivors returned follow-up questionnaires at 9 months (84.1% in the intervention arm and 75.8% in the usual care arm, green); according to data reported by sites, overall, 95.2% of registered stroke survivors were offered at least one session of the intervention (green); all five intervention sites had at least two facilitators deemed competent, delivered the New Start intervention and provided it to stroke survivors (green). However, at some sites, there were concerns regarding the number of stroke survivors being offered, accepting and receiving the intervention. Only small differences in outcomes and costs were observed between the New Start and usual care groups, and considerable uncertainty around the cost-effectiveness remains. Conclusions: We report a complex programme of work that has described the longer-term needs of stroke survivors and highlighted evidence and service gaps. Working closely with stroke survivors, an intervention was developed that has been refined in three services and feasibility tested in a cluster randomised controlled trial. Further refinement of the target population and optimisation of the intervention materials is required prior to a full randomised controlled trial evaluation. Future work: Optimisation of the intervention, and clearer specification of recipients, are required prior to a full trial evaluation. Trial registration: Current Controlled Trials ISRCTN38920246. Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 3. See the NIHR Journals Library website for further project information.

It is often said that understanding humor in a language is the highest sign of fluency. Comprehending de dicto jokes, specifically, demonstrates our tacit knowledge of and competence in that language. In Aarons’s Jokes and the Linguistic Mind, multitudinous examples of humor are examined in regard to the wide range of linguistic concepts they address. The text is based on Chomsky’s (1965) definition of competence as our implicit knowledge of the rules of language; it aims to show that when, for example, a joke about the ambiguity of a certain article is funny, it is precisely because it brings a rule governing article use to our consciousness. Aarons’ detailed analyses of jokes play on semantic, phonologic, pragmatic, and syntactic rules, and are therefore of interest to the linguist. At the same time, her analyses are of equal importance to the language teacher, considering that many of these rules and explanations are of pedagogical use.

It is often said that understanding humor in a language is the highest sign of fluency. Comprehending de dicto jokes, specifically, demonstrates our tacit knowledge of and competence in that language. In Aarons’s Jokes and the Linguistic Mind, multitudinous examples of humor are examined in regard to the wide range of linguistic concepts they address. The text is based on Chomsky’s (1965) definition of competence as our implicit knowledge of the rules of language; it aims to show that when, for example, a joke about the ambiguity of a certain article is funny, it is precisely because it brings a rule governing article use to our consciousness. Aarons’ detailed analyses of jokes play on semantic, phonologic, pragmatic, and syntactic rules, and are therefore of interest to the linguist. At the same time, her analyses are of equal importance to the language teacher, considering that many of these rules and explanations are of pedagogical use.

The latest volume in the Language Planning and Policy series, co-edited by Baldauf and Kaplan, deals with three Latin American countries, Ecuador, Mexico, and Paraguay, which, while not geographically close, do share several key factors in relation to their language situation and corresponding governmental policy. Previous books in this series on Africa, Asia, and Europe have dealt with similar issues of linguistic diversity and political context, yet the study of these Latin American countries offers the unique and distinguishing characteristic of one official language impacting three separate countries. The objective of these studies, and in fact the series, is to address roughly two-dozen questions that bring to light the nature of language in these countries. The editors organize the questions into four sections: language profile, language spread, language policy and planning, and language maintenance and prospects.

Abstract Host-parasite interactions exert strong selection pressures on the genomes of both host and parasite. These interactions can lead to negative frequency-dependent selection, a form of balancing selection that is hypothesised to explain the high levels of polymorphism seen in many host immune and parasite antigen loci. Here, we sequence the genomes of several individuals of Heligmosomoides bakeri, a model parasite of house mice, and Heligmosomoides polygyrus, a closely related parasite of wood mice. Although H. bakeri is commonly referred to as H. polygyrus in the literature, their genomes show levels of divergence that are consistent with at least a million years of independent evolution. The genomes of both species contain hyper-divergent haplotypes that are enriched for proteins that interact with the host immune response. Many of these haplotypes originated prior to the divergence between H. bakeri and H. polygyrus, suggesting that they have been maintained by long-term balancing selection. Together, our results suggest that the selection pressures exerted by the host immune response have played a key role in shaping patterns of genetic diversity in the genomes of parasitic nematodes.

Centre-based childcare may benefit pre-school children and alleviate inequalities in early childhood development, but evidence on socio-emotional and physical health outcomes is limited. Data were from the UK Millennium Cohort Study (n = 14,376). Inverse-probability weighting was used to estimate confounder-adjusted population-average effects of centre and non-centre-based childcare (compared to parental care only) between ages 26–31 months on (age 3): internalising and externalising symptoms, pro-social behaviour, independence, emotional dysregulation, vocabulary, school readiness, and body mass index. To assess impacts on inequalities, controlled direct effects of low parental education and lone parenthood on all outcomes were estimated under two hypothetical scenarios: 1) universal take-up of centre-based childcare; and 2) parental care only. On average, non-centre based childcare improved vocabulary and centre-based care improved school readiness, with little evidence of other benefits. However, socio-economic inequalities were observed for all outcomes and were attenuated in scenario 1 (universal take-up). For example, inequalities in externalising symptoms (according to low parental education) were reduced from a confounder-adjusted standard deviation difference of 7.8 (95% confidence intervals: 6.7–8.8), to 1.7 (0.6–2.7). Inequalities by parental education in scenario 2 (parental care only) were wider than in scenario 1 for externalising symptoms (at 3.4; 2.4–4.4), and for emotional dysregulation and school readiness. Inequalities by lone parenthood, which were smaller, fell in scenario 1, and fell further in scenario 2. Universal access to centre-based pre-school care may alleviate inequalities, while restricted access (e.g. during lockdown for a pandemic such as Covid-19) may widen some inequalities in socioemotional and cognitive development.

Recent studies have demonstrated that many parasites release extracellular vesicles (EVs), yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show that EVs secreted by the gastrointestinal nematode Heligmosomoides polygyrus are internalized by macrophages and modulate their activation. EV internalization causes downregulation of type 1 and type 2 immune-response-associated molecules (IL-6 and TNF, and Ym1 and RELMα) and inhibits expression of the IL-33 receptor subunit ST2. Co-incubation with EV antibodies abrogated suppression of alternative activation and was associated with increased co-localization of the EVs with lysosomes. Furthermore, mice vaccinated with EV-alum generated protective immunity against larval challenge, highlighting an important role in vivo. In contrast, ST2-deficient mice are highly susceptible to infection, and they are unable to clear parasites following EV vaccination. Hence, macrophage activation and the IL-33 pathway are targeted by H. polygyrus EVs, while neutralization of EV function facilitates parasite expulsion.

Over 25% of the world's population are infected with helminth parasites, the majority of which colonise the gastrointestinal tract. However, no vaccine is yet available for human use, and mechanisms of protective immunity remain unclear. In the mouse model of Heligmosomoides polygyrus infection, vaccination with excretory-secretory (HES) antigens from adult parasites elicits sterilising immunity. Notably, three purified HES antigens (VAL-1, -2 and -3) are sufficient for effective vaccination. Protection is fully dependent upon specific IgG1 antibodies, but passive transfer confers only partial immunity to infection, indicating that cellular components are also required. Moreover, immune mice show greater cellular infiltration associated with trapping of larvae in the gut wall prior to their maturation. Intra-vital imaging of infected intestinal tissue revealed a four-fold increase in extravasation by LysM+GFP+ myeloid cells in vaccinated mice, and the massing of these cells around immature larvae. Mice deficient in FcRγ chain or C3 complement component remain fully immune, suggesting that in the presence of antibodies that directly neutralise parasite molecules, the myeloid compartment may attack larvae more quickly and effectively. Immunity to challenge infection was compromised in IL-4Rα- and IL-25-deficient mice, despite levels of specific antibody comparable to immune wild-type controls, while deficiencies in basophils, eosinophils or mast cells or CCR2-dependent inflammatory monocytes did not diminish immunity. Finally, we identify a suite of previously uncharacterised heat-labile vaccine antigens with homologs in human and veterinary parasites that together promote full immunity. Taken together, these data indicate that vaccine-induced immunity to intestinal helminths involves IgG1 antibodies directed against secreted proteins acting in concert with IL-25-dependent Type 2 myeloid effector populations.