The lung collectin surfactant protein D (SP-D) is an important component of the innate immune response but is also believed to play a role in other regulatory aspects of immune and inflammatory responses within the lung. The role of SP-D in the development of allergen-induced airway inflammation and hyperresponsiveness (AHR) is not well defined. SP-D levels progressively increased up to 48 hours after allergen challenge of sensitized mice and then subsequently decreased. The levels of SP-D paralleled the development of airway eosinophilia and AHR. To determine if this association was functionally relevant, mice were administered rat SP-D (rSP-D) intratracheally. When given to sensitized mice before challenge, AHR and eosinophilia were reduced by rSP-D in a dose-dependent manner but not by mutant rSP-D. rSP-D administration resulted in increased levels of interleukin (IL)-10, IL-12, and IFN-gamma in bronchoalveolar lavage fluid and reduced goblet cell hyperplasia. Culture of alveolar macrophages together with SP-D and allergen resulted in increased production of IL-10, IL-12, and IFN-gamma. These results indicate that SP-D can (negatively) regulate the development of AHR and airway inflammation after airway challenge of sensitized mice, at least in part, by modulating the function of alveolar macrophages.

This paper explores what motivates improved health care performance. Previously, many have thought that performance would either improve via choice and competition or by relying on trust and altruism. But neither assumption is supported by available evidence. So instead we explore a third approach of reciprocal altruism with sanctions for unacceptably poor performance and rewards for high performance. These rewards and sanctions, however, are not monetary, but in the form of reputational effects through public reporting of benchmarking of performance. Drawing on natural experiments in Italy and the United Kingdom, we illustrate how public benchmarking can improve poor performance at the national level through 'naming and shaming' and enhance good performance at the sub-national level through 'competitive benchmarking' and peer learning. Ethnographic research in Zambia also showed how reputations count. Policy-makers could use these effects in different ways to improve public services.

Key Points• Recombinant antibody B2G1Dnab protects platelets from destruction by anti-HPA-1a in the circulation of HPA-1a1b human volunteers.• B2G1Dnab is a potential therapeutic agent for antenatal treatment of fetomaternal alloimmune thrombocytopenia due to HPA-1a antibodies.Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal human platelet antigen-1a (HPA-1a), can result in intracranial hemorrhage and intrauterine death. We have developed a therapeutic human recombinant high-affinity HPA-1a antibody (B2G1Dnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fcg receptors. In vitro studies with a range of clinical anti-HPA-1a sera have shown that B2G1Dnab blocks monocyte chemiluminescence by >75%. In this firstin-man study, we demonstrate that HPA-1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1Dnab have the same intravascular survival as unsensitized platelets (190 hours), while platelets sensitized with a destructive immunoglobulin G1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1Dnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA-1a antibody) and B2G1Dnab survive 3 times as long in circulation compared with platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1Dnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunization in HPA-1a-negative mothers. (Blood. 2013;122(3):313-320)

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This paper reexamines why global collective action problems persist, and how to overcome them. Drawing on 140 interviews with campaigners, politicians, and businesses in 10 European countries, it suggests that many activists are stuck in a despondency trap. Never seeing radical reform, they lower their ambitions, and invest in more feasible but sub-optimal alternatives. This creates a negative feedback loop, in which the dearth of radical reform becomes self-fulfilling. But if reformists see advances at home and abroad, they may become more optimistic about collective mobilisation and break out of their despondency trap. This is shown by tracing the drivers of groundbreaking legislation. From 2018, large French firms must mitigate risks of environmental and human rights abuses in their global supply chains, or else be liable. This billthe world's first of its kind-was vociferously contested by businesses. But French campaigners and politicians persisted for four years, because they saw reasons for optimism. These include growing international support; public outcry; the French political culture (state intervention, and distrust of multinationals); together with a Centre-Left Government. Optimism galvanised relentless mobilisation. Legislative success in France then delivered a positive shock to activists across Europe, who were emboldened to launch similar campaigns and escape their despondency trap. I am extremely grateful to my Belgian, Britain, Dutch, French, German and Swiss participants, who shared their reflections with me, and provided useful comments on earlier drafts. This article has greatly benefited from constructive criticism from Michaël Aklin,