Two prototypic types of virus-specific CD8+ T cells can be found in latently infected individuals: CD45R0+CD27+CCR7− effector-memory, and CD45RA+CD27−CCR7− effector-type cells. It has recently been implied that CD45RA+CD27−CCR7− T cells are terminally differentiated effector cells and as such have lost all proliferative capacity. We show in this study, however, that stimulation of CMV-specific CD45RA+CD27−CCR7− T cells with their cognate peptide in concert with either CD4+ help or IL-2, IL-15, or IL-21 in fact induces massive clonal expansion. Concurrently, these stimulated effector T cells change cell surface phenotype from CD45RA to CD45R0 and regain CCR7, while effector functions are maintained. Our data imply that CD45RA+CD27−CCR7− effector-type T cells contribute to immunity not only by direct execution of effector functions, but also by yielding progeny in situations of viral reinfection or reactivation.

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This paper draws the attention to the use of urban land use as a promising and new playground for urban green space design, including viable small-scale agricultural activities. First, an overview of urban green space planning is given, followed by a typology of approaches to evaluate urban green space. Next, the specific importance of urban green space for small-scale agriculture and horticulture is highlighted. The paper concludes with an elaboration of the rich multi-tasking performance of urban green space for a modern urbanized society.

IntroductionInduced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest.MethodsA prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at three time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined.ResultsIn total, 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C.ConclusionsPatients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest.Trial registrationClinicalTrials.gov NCT01020916, registered 25 November 2009

Iterative Proportional Fitting (IPF), also known as biproportional fitting, 'raking' or the RAS algorithm, is an established procedure used in a variety of applications across the social sciences. Primary amongst these for urban modelling has been its use in static spatial microsimulation to generate small area microdata -individual level data allocated to administrative zones. The technique is mature, widely used and relatively straight-forward. Although IPF is well described mathematically, accessible examples of the algorithm written in modern programming languages are rare. There is a tendency for researchers to 'start from scratch', resulting in a variety of ad hoc implementations and little evidence about the relative merits of differing approaches. These knowledge gaps mean that answers to certain methodological questions must be guessed: How can 'empty cells' be identified and how do they influence model fit? Can IPF be made more computationally efficient? This paper tackles these questions and more using a systematic methodology with publicly available code and data. The results demonstrate the sensitivity of the results to initial conditions, notably the presence of 'empty cells', and the dramatic impact of software decisions on computational efficiency. The paper concludes by proposing an agenda for robust and transparent future tests in the field.

The varied supply of tourism services -with particular emphasis on tangible and intangible cultural aspects -corresponds ideally to visitors' characteristics and wishes. This paper considers a major tourist destination, such as Amsterdam, as an export-oriented multiproduct company, characterized by spatial and functional market segmentation and monopolistic competition reflected in product differentiation. Urban branding and attractiveness may favour tourist destination loyalty. The complex decision web of motivation and satisfaction of tourists in Amsterdam is analysed with a structural equations model (SEM). The authors find that different tourist profiles, in terms of personal characteristics and motivations, can significantly impact the satisfaction received from tourism services. Furthermore, and most interestingly, the results suggest that satisfaction does not necessarily lead to improved destination loyalty, but is contingent on the source of satisfaction. In this case, satisfaction resulting from tangible or intangible cultural sources has clearly different implications for loyalty, with relevant managerial implications.

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