Coastal Lagoons and Climate Change: Ecological and Social Ramifications in the U.S. Atlantic and Gulf Coast Ecosystems

Lagoons are highly productive coastal features that provide a range of natural services that society values. Their setting within the coastal landscape leaves them especially vulnerable to profound physical, ecological, and associated societal disturbance from global climate change. Expected shifts in physical and ecological characteristics range from changes in flushing regime, freshwater inputs, and water chemistry to complete inundation and loss and the concomitant loss of natural and human communities. Therefore, managing coastal lagoons in the context of global climate change is critical. Although management approaches will vary depending on local conditions and cultural norms, all management scenarios will need to be nimble and to make full use of the spectrum of values through which society views these unique ecosystems. We propose that this spectrum includes pragmatic, scholarly, aesthetic, and tacit categories of value. Pragmatic values such as fishery or tourism revenue are most easily quantified and are therefore more likely to be considered in management strategies. In contrast, tacit values such as a sense of place are more difficult to quantify and therefore more likely to be left out of explicit management justifications. However, tacit values are the most influential to stakeholder involvement because they both derive from and shape individual experiences and beliefs. Tacit values underpin all categories of social values that we describe and can be expected to have a strong influence over human behavior. The articulation and inclusion of the full spectrum of values, especially tacit values, will facilitate and support nimble adaptive management of coastal lagoon ecosystems in the context of global climate change

Bridge to the stars: A mission concept to an interstellar object

Exoplanet discoveries since the mid-1990’s have revealed an astounding diversity of planetary systems. Studying these systems is essential to understanding planetary formation processes, as well as the development of life in the universe. Unfortunately, humanity can only observe limited aspects of exoplanetary systems by telescope, and the significant distances between stars presents a barrier to in situ exploration. In this study, we propose an alternative path to gain insight into exoplanetary systems: Bridge, a mission concept design to fly by an interstellar object as it passes through our solar system. Designed as a New Frontiers-class mission during the National Aeronautics and Space Administration (NASA) Planetary Science Summer School, Bridge would provide a unique opportunity to gain insight into potential physical, chemical, and biological differences between solar systems as well as the possible exchange of planetary materials between them. Bridge employs ultraviolet/visible, near-infrared, and mid-infrared point spectrometers, a visible camera, and a guided impactor. We also provide a quantitative Monte Carlo analysis that estimates wait times for a suitable target, and examines key trades between ground storage and a parking orbit, power sources, inner versus outer solar system encounters, and launch criteria. Due to the fleeting nature of interstellar objects, reaching an interstellar object may require an extended ground storage phase for the spacecraft until a suitable ISO is discovered, followed by a rapid response launch strategy. To enable rapid response missions designed to intercept such unique targets, language would need to be added to future NASA announcements of opportunity such that ground storage and rapid response would be allowable components of a proposed mission

Determining Risk for Severe Leptospirosis by Molecular Analysis of Environmental Surface Waters for Pathogenic Leptospira

BACKGROUND: Although previous data indicate that the overall incidence of human leptospirosis in the Peruvian Amazon is similar in urban and rural sites, severe leptospirosis has been observed only in the urban context. As a potential explanation for this epidemiological observation, we tested the hypothesis that concentrations of more virulent Leptospira would be higher in urban than in rural environmental surface waters. METHODS AND FINDINGS: A quantitative real-time PCR assay was used to compare levels of Leptospira in urban and rural environmental surface waters in sites in the Peruvian Amazon region of Iquitos. Molecular taxonomic analysis of a 1,200-bp segment of the leptospiral 16S ribosomal RNA gene was used to identify Leptospira to the species level. Pathogenic Leptospira species were found only in urban slum water sources (Fisher's exact test; p = 0.013). The concentration of pathogen-related Leptospira was higher in urban than rural water sources (~10(3) leptospires/ml versus 0.5 × 10(2) leptospires/ml; F = 8.406, p < 0.05). Identical 16S rRNA gene sequences from Leptospira interrogans serovar Icterohaemorrhagiae were found in urban slum market area gutter water and in human isolates, suggesting a specific mode of transmission from rats to humans. In a prospective, population-based study of patients presenting with acute febrile illness, isolation of L. interrogans-related leptospires from humans was significantly associated with urban acquisition (75% of urban isolates); human isolates of other leptospiral species were associated with rural acquisition (78% of rural isolates) (chi-square analysis; p < 0.01). This distribution of human leptospiral isolates mirrored the distribution of leptospiral 16S ribosomal gene sequences in urban and rural water sources. CONCLUSIONS: Our findings data support the hypothesis that urban severe leptospirosis in the Peruvian Amazon is associated with higher concentrations of more pathogenic leptospires at sites of exposure and transmission. This combined quantitative and molecular taxonomical risk assessment of environmental surface waters is globally applicable for assessing risk for leptospiral infection and severe disease in leptospirosis-endemic regions

Development and Validation of a Real-Time PCR for Detection of Pathogenic Leptospira Species in Clinical Materials

Available serological diagnostics do not allow the confirmation of clinically suspected leptospirosis at the early acute phase of illness. Several conventional and real-time PCRs for the early diagnosis of leptospirosis have been described but these have been incompletely evaluated. We developed a SYBR Green-based real-time PCR targeting secY and validated it according to international guidelines. To determine the analytical specificity, DNA from 56 Leptospira strains belonging to pathogenic, non-pathogenic and intermediate Leptospira spp. as well as 46 other micro-organisms was included in this study. All the pathogenic Leptospira gave a positive reaction. We found no cross-reaction with saprophytic Leptospira and other micro-organisms, implying a high analytical specificity. The analytical sensitivity of the PCR was one copy per reaction from cultured homologous strain M 20 and 1.2 and 1.5 copy for heterologous strains 1342 K and Sarmin, respectively. In spiked serum & blood and kidney tissue the sensitivity was 10 and 20 copies for M 20, 15 and 30 copies for 1342 K and 30 and 50 copies for Sarmin. To determine the diagnostic sensitivity (DSe) and specificity (DSp), clinical blood samples from 26 laboratory-confirmed and 107 negative patients suspected of leptospirosis were enrolled as a prospective consecutive cohort. Based on culture as the gold standard, we found a DSe and DSp of 100% and 93%, respectively. All eight PCR positive samples that had a negative culture seroconverted later on, implying a higher actual DSp. When using culture and serology as the gold standard, the DSe was lower (89%) while the DSp was higher (100%). DSe was 100% in samples collected within the first – for treatment important - 4 days after onset of the illness. Reproducibility and repeatability of the assay, determined by blind testing kidney samples from 20 confirmed positive and 20 negative rodents both appeared 100%. In conclusion we have described for the first time the development of a robust SYBR Green real-time PCR for the detection of pathogenic Leptospira combined with a detailed assessment of its clinical accuracy, thus providing a method for the early diagnosis of leptospirosis with a well-defined satisfactory performance

Long-term Remissions Following CD20-directed Chimeric Antigen Receptor Adoptive T cell Therapy

Chimeric antigen receptor (CAR) T cell therapy produces high response rates in refractory B-cell non-Hodgkin lymphoma (NHL), but long-term data are minimal to date. Here, we present long-term follow-up of a pilot trial testing a CD20-targeting 3rd generation CAR in patients with relapsed B-cell lymphomas following cyclophosphamide-only lymphodepletion. Two of the 3 patients in the trial, with mantle cell lymphoma and follicular lymphoma, had remissions lasting more than 7 years, though they ultimately relapsed. The absence of B cell aplasia in both patients suggested a lack of functional CAR T cell persistence, leading to the hypothesis that endogenous immune responses were responsible for these long remissions. Correlative immunologic analyses supported this hypothesis, with evidence of new humoral and cellular anti-tumor immune responses proximal to clinical response time points. Collectively, our results suggest that CAR T cell therapy may facilitate epitope spreading and endogenous immune response formation in lymphomas

Neoantigen-specific CD4 + T cells in human melanoma have diverse differentiation states and correlate with CD8 + T cell, macrophage, and B cell function

CD4+ T cells that recognize tumor antigens are required for immune checkpoint inhibitor efficacy in murine models, but their contributions in human cancer are unclear. We used single-cell RNA sequencing and T cell receptor sequences to identify signatures and functional correlates of tumor-specific CD4+ T cells infiltrating human melanoma. Conventional CD4+ T cells that recognize tumor neoantigens express CXCL13 and are subdivided into clusters expressing memory and T follicular helper markers, and those expressing cytolytic markers, inhibitory receptors, and IFN-γ. The frequency of CXCL13+ CD4+ T cells in the tumor correlated with the transcriptional states of CD8+ T cells and macrophages, maturation of B cells, and patient survival. Similar correlations were observed in a breast cancer cohort. These results identify phenotypes and functional correlates of tumor-specific CD4+ T cells in melanoma and suggest the possibility of using such cells to modify the tumor microenvironment