What causes the spread of model projections of ocean dynamic sea-level change in response to greenhouse gas forcing?

Sea levels of different atmosphere-ocean general circulation models (AOGCMs) respond to climate change forcing in different ways, representing a crucial uncertainty in climate change research. We isolate the role of the ocean dynamics in setting the spatial pattern of dynamic sea-level (zeta) change by forcing several AOGCMs with prescribed identical heat, momentum (wind) and freshwater flux perturbations. This method produces a zeta projection spread comparable in magnitude to the spread that results from greenhouse gas forcing, indicating that the differences in ocean model formulation are the cause, rather than diversity in surface flux change. The heat flux change drives most of the global pattern of zeta change, while the momentum and water flux changes cause locally confined features. North Atlantic heat uptake causes large temperature and salinity driven density changes, altering local ocean transport and zeta. The spread between AOGCMs here is caused largely by differences in their regional transport adjustment, which redistributes heat that was already in the ocean prior to perturbation. The geographic details of the zeta change in the North Atlantic are diverse across models, but the underlying dynamic change is similar. In contrast, the heat absorbed by the Southern Ocean does not strongly alter the vertically coherent circulation. The Arctic zeta change is dissimilar across models, owing to differences in passive heat uptake and circulation change. Only the Arctic is strongly affected by nonlinear interactions between the three air-sea flux changes, and these are model specific.Peer reviewe

Natural and Vaccine-Mediated Immunity to Salmonella Typhimurium is Impaired by the Helminth Nippostrongylus brasiliensis

The impact of exposure to multiple pathogens concurrently or consecutively on immune function is unclear. Here, immune responses induced by combinations of the bacterium Salmonella Typhimurium (STm) and the helminth Nippostrongylus brasiliensis (Nb), which causes a murine hookworm infection and an experimental porin protein vaccine against STm, were examined. Mice infected with both STm and Nb induced similar numbers of Th1 and Th2 lymphocytes compared with singly infected mice, as determined by flow cytometry, although lower levels of secreted Th2, but not Th1 cytokines were detected by ELISA after re-stimulation of splenocytes. Furthermore, the density of FoxP3+ T cells in the T zone of co-infected mice was lower compared to mice that only received Nb, but was greater than those that received STm. This reflected the intermediate levels of IL-10 detected from splenocytes. Co-infection compromised clearance of both pathogens, with worms still detectable in mice weeks after they were cleared in the control group. Despite altered control of bacterial and helminth colonization in co-infected mice, robust extrafollicular Th1 and Th2-reflecting immunoglobulin-switching profiles were detected, with IgG2a, IgG1 and IgE plasma cells all detected in parallel. Whilst extrafollicular antibody responses were maintained in the first weeks after co-infection, the GC response was less than that in mice infected with Nb only. Nb infection resulted in some abrogation of the longer-term development of anti-STm IgG responses. This suggested that prior Nb infection may modulate the induction of protective antibody responses to vaccination. To assess this we immunized mice with porins, which confer protection in an antibody-dependent manner, before challenging with STm. Mice that had resolved a Nb infection prior to immunization induced less anti-porin IgG and had compromised protection against infection. These findings demonstrate that co-infection can radically alter the development of protective immunity during natural infection and in response to immunization

Low overhead alternatives to SSS

Of the many minimax algorithms, SSS* is noteworthy because it usually searches the smallest game trees. Its success can be attributed to the accumulation and use of information acquired while traversing the tree. The main disadvantages of SSS* are its high storage needs and management costs. This paper describes a class of methods, based on the popular alpha-beta algorithm, that acquire and use information to guide a tree search. They retain a given search direction and yet are as good as SSS*, even while searching random trees. Further, although some of these new algorithms also require substantial storage, they are more flexible and can be programmed to use onl

The burden of chronic spontaneous urticaria is substantial : real-world evidence from ASSURE-CSU

Chronic spontaneous urticaria () can be debilitating, difficult to treat, and frustrating for patients and physicians. Real-world evidence for the burden of is limited. The objective of this study was to document disease duration, treatment history, and disease activity, as well as impact on health-related quality of life (oL) and work among patients with inadequately controlled , and to describe its humanistic, societal, and economic burden. This international observational study assessed a cohort of 673 adult patients with whose symptoms persisted for ≥12 months despite treatment. Demographics, disease characteristics, and healthcare resource use in the previous 12 months were collected from medical records. Patient-reported data on urticaria and angioedema symptoms, oL, and work productivity and activity impairment were collected from a survey and a diary. Almost 50% of patients had moderate-to-severe disease activity as reported by Urticaria Activity Score. Mean () Dermatology Life Quality Index and Chronic Urticaria Quality of Life Questionnaire scores were 9.1 (6.62) and 33.6 (20.99), respectively. Chronic spontaneous urticaria markedly interfered with sleep and daily activities. Angioedema in the previous 12 months was reported by 66% of enrolled patients and significantly affected oL. More than 20% of patients reported ≥1 hour per week of missed work; productivity impairment was 27%. These effects increased with increasing disease activity. Significant healthcare resources and costs were incurred to treat . Chronic spontaneous urticaria has considerable humanistic and economic impacts. Patients with greater disease activity and with angioedema experience greater oL impairments