Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential

Human IgG3 displays the strongest effector functions of all IgG subclasses but has a short half-life for unresolved reasons. Here we show that IgG3 binds to IgG-salvage receptor (FcRn), but that FcRn-mediated transport and rescue of IgG3 is inhibited in the presence of IgG1 due to intracellular competition between IgG1 and IgG3. We reveal that this occurs because of a single amino acid difference at position 435, where IgG3 has an arginine instead of the histidine found in all other IgG subclasses. While the presence of R435 in IgG increases binding to FcRn at neutral pH, it decreases binding at acidic pH, affecting the rescue efficiency—but only in the presence of H435–IgG. Importantly, we show that in humans the half-life of the H435-containing IgG3 allotype is comparable to IgG1. H435–IgG3 also gave enhanced protection against a pneumococcal challenge in mice, demonstrating H435–IgG3 to be a candidate for monoclonal antibody therapies

Socio-economic class, rurality and risk of cutaneous melanoma by site and gender in Sweden

<p>Abstract</p> <p>Background</p> <p>Cutaneous melanoma (CM) is a cancer usually associated with high socio-economic level in the literature. Few studies have, however, assessed this relationship by gender and site or the association between CM and rurality.</p> <p>Methods</p> <p>A major-sized historical occupational Swedish cohort comprising 2,992,166 workers was used to estimate relative risk of cutaneous melanoma, broken down by gender and anatomical site, for occupational sectors (as a proxy of socio-economic class) and rurality. To this end, Poisson models were fitted for each site in men and women, including occupational sector and town size, with adjustment for age, period of diagnosis and geographical area as possible confounding factors.</p> <p>Results</p> <p>White collar workers presented a marked increased of risk in men in all melanoma cases, as well as in trunk, upper and lower limbs. This pattern was less clear for women, in which some heterogeneity appeared, as low risks in lower socioeconomic sectors in trunk, or risk excesses in white collar workers in lower limbs did not achieve statistical significance. Males also showed significant differences in risk by rural/urban distribution, but in women this association was limited to CM of lower limb. Risk of CM of head/neck did not vary by occupational sector or town size, thus depicting a specific epidemiological profile, which proved common to both sexes.</p> <p>Conclusion</p> <p>While differences in risk between men and women could suggest greater homogeneity in UV-exposure behaviour among women, the uniform risk pattern in head and neck melanoma, present in both sexes, might support the coexistence of different aetiological pathways, related to anatomical site.</p

Windbreaks in North American Agricultural Systems

Windbreaks are a major component of successful agricultural systems throughout the world. The focus of this chapter is on temperate-zone, commercial, agricultural systems in North America, where windbreaks contribute to both producer profitability and environmental quality by increasing crop production while simultaneously reducing the level of off-farm inputs. They help control erosion and blowing snow, improve animal health and survival under winter conditions, reduce energy consumption of the farmstead unit, and enhance habitat diversity, providing refuges for predatory birds and insects. On a larger landscape scale windbreaks provide habitat for various types of wildlife and have the potential to contribute significant benefits to the carbon balance equation, easing the economic burdens associated with climate change. For a windbreak to function properly, it must be designed with the needs of the landowner in mind. The ability of a windbreak to meet a specific need is determined by its structure: both external structure, width, height, shape, and orientation as well as the internal structure; the amount and arrangement of the branches, leaves, and stems of the trees or shrubs in the windbreak. In response to windbreak structure, wind flow in the vicinity of a windbreak is altered and the microclimate in sheltered areas is changed; temperatures tend to be slightly higher and evaporation is reduced. These types of changes in microclimate can be utilized to enhance agricultural sustainability and profitability. While specific mechanisms of the shelter response remain unclear and are topics for further research, the two biggest challenges we face are: developing a better understanding of why producers are reluctant to adopt windbreak technology and defining the role of woody plants in the agricultural landscape

A Program for At-Risk High School Students Informed by Evolutionary Science

Improving the academic performance of at-risk high school students has proven difficult, often calling for an extended day, extended school year, and other expensive measures. Here we report the results of a program for at-risk 9th and 10th graders in Binghamton, New York, called the Regents Academy that takes place during the normal school day and year. The design of the program is informed by the evolutionary dynamics of cooperation and learning, in general and for our species as a unique product of biocultural evolution. Not only did the Regents Academy students outperform their comparison group in a randomized control design, but they performed on a par with the average high school student in Binghamton on state-mandated exams. All students can benefit from the social environment provided for at-risk students at the Regents Academy, which is within the reach of most public school districts

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

Patient and family perspectives in resilient healthcare studies: A question of morality or logic?

Whilst interest in resilient healthcare (RHC) research has increased over the past five years, our understanding of the role of patients, families and carers in supporting system resilience remains limited (Berg et al., 2018; Laugaland and Aase, 2015). The extant empirical evidence for RHC has almost exclusively been undertaken from the perspective of staff. However, evidence is emerging suggesting that patients, families and carers impact on variability and outcomes within complex health systems, and as such could be regarded as co-creators of resilience (Schubert et al., 2015; O’Hara et al., 2019). Within health services research and improvement, engagement of patients and the public is widespread, with an ever building evidence base examining how, and in what ways such engagement should be done (Kirwan et al., 2017). Thus, as it grows as a discipline, there is no doubt that this ‘moral’ argument for the involvement of patients and families in RHC research will increase. However, in this paper we argue that whilst involving patients and families in RHC research clearly remains a moral imperative, it is also – and perhaps as importantly – driven by the logic of doing so. We view the integration of patient and family perspectives in RHC studies, as comprising two discrete, but not mutually exclusive approaches: (i) Patient and family ‘involvement’ in RHC studies, as co-creators of evidence; and, (ii) exploring and modeling patient and family ‘functional activity’ within systems, recognising their role as co-creators of resilience. We will discuss six case studies of RHC research: two that explore the role of patient and family activity within systems, and four that do not view patient and family activity as part of the system. Our aim is to demonstrate how without these perspectives, our understanding of work-as-done may be limited, and not account for variability introduced by these key actors within the system, that both supports, and compromises, the resilience of that system. In short, without understanding this variability we risk misunderstanding the resilience of our healthcare systems. Drawing on the case study examples, we present a planning support tool for the involvement of patient and family perspectives in RHC studies, which will provide practical guidance to support decisions about when, and how, to explore and document patient and family activity within systems. As key stakeholders in healthcare systems, patients and families should always be involved as co-creators of evidence in RHC studies. However, here we argue that for most healthcare systems, they are likely to additionally be co-creators of resilience

Is sustainable development a practical possibility given the continued use of plant protection products? The scientific view

Considering the fact that plant protection products generally are active ingredients with biocidal properties they have to have effects at least in the target environment. Sustainability in agriculture requires that agricultural arm keep their facility and that effects outside the target areas at least reversible. This requires for a continued use of plant protection products that application technologies have to be optimised for minimum release into ecotons and to exhibit properties not resulting in long-term impacts (degradability, no bioaccumulation etc.). Furthermore when considering sustainability the different agricultural technologies should be weighted against each other as compared to their effects on soil fertility and ecological consequences. This means that plant protection products should be compared with tillaging, crop rotation, fertilisation-intensity of agriculture, alternative plant protection methods. ratio of use versus refugial areas in a region, use of genetically modified resistant crops, comparison of commercial costs, ecological costs and benefit. Some of this criteria will be substantiated by examples