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Martinus Kosters’ rejoinder to my article, “Tourism and Political Science: A Case of Not so Benign Neglect” really leaves me without any excuse to reply. His appraisal is generous, certainly requiring no rebuttal on my part. His critique of my neglect of European tourism conditions is both accurate and well-argued. I am exercising my opportunity to reply, therefore, not to defend my article, but to continue the kind of dialogue which simply must take place if we are to develop research agenda for exploring the politics of tourism systematically. If Kosters is correct about the even more appalling state of neglect of tourism politics in Europe than in the United States, then the prospects for political research on tourism are more grim than I anticipated. Perhaps naively, I assumed that once the economic importance of tourism was fully appreciated, the political ramifications would be similarly recognized. However, Europe has long recognized the economic importance of tourism, and its several institutes of tourism and tourism journals testify to a longstanding interest in the subject. If the impact of tourism has failed to intrigue the political scientists of Europe, then simply the expansion of tourism within the United States or our growing dependence on international tourism to ameliorate our balance of payments deficit will scarcely suffice. It is easy to appreciate how discouraging it must be for individuals like Senator Daniel Inouye (USA), who spent a decade gently guiding the National Tourism Policy Act through Congress, to see the results of their labor. For years Inouye’s congressional committee heard testimony detailing the staggering importance of tourism to the society, to employment rates, to our tax revenue and balance of payments. One administration after another hardly yawned in reply. Finally in 198 1 President Reagan signed the first National Tourism Act commiting the nation to an attempt to coordinate tourism’s development in conjunction with other sometimes conflicting national policies. A new era? At last political recognition for the nation’s second largest retail industry? Scarcely. In hisnext two budget messages, the President’s recommendations proposed to gut funding for the new U.S Travel and Tourism Administration (USTTA). President Reagan is famous for cost-cutting of domestic programs, but cutting an agency designed to increase revenues, increase employment, and increase foreign trade is scarcely consistent with the President’s avowed desire to stimulate the economy. Moreover, as a busi

Background Juvenile Idiopathic Arthritis (JIA) is an autoimmune disease with a heterogenous clinical presentation and unpredictable response to available therapies. This personalized transcriptomics study sought proof-of-concept for single-cell RNA sequencing to characterize patient-specific immune profiles. Methods Whole blood samples from six untreated children, newly diagnosed with JIA, and two healthy controls were cultured for 24 h with or without ex vivo TNF stimulation and subjected to scRNAseq to examine cellular populations and transcript expression in PBMCs. A novel analytical pipeline, scPool, was developed wherein cells are first pooled into pseudocells prior to expression analysis, facilitating variance partitioning of the effects of TNF stimulus, JIA disease status, and individual donor. Results Seventeen robust immune cell-types were identified, the abundance of which was significantly affected by TNF stimulus, which resulted in notable elevation of memory CD8 + T-cells and NK56 cells, but down-regulation of naïve B-cell proportions. Memory CD8 + and CD4 + T-cells were also both reduced in the JIA cases relative to two controls. Significant differential expression responses to TNF stimulus were also characterized, with monocytes showing more transcriptional shifts than T-lymphocyte subsets, while the B-cell response was more limited. We also show that donor variability exceeds the small degree of possible intrinsic differentiation between JIA and control profiles. An incidental finding of interest was association of HLA-DQA2 and HLA-DRB5 expression with JIA status. Conclusions These results support the development of personalized immune-profiling combined with ex-vivo immune stimulation for evaluation of patient-specific modes of immune cell activity in autoimmune rheumatic disease.

Signal transducer and activator of transcription 5 (STAT5a and STAT5b) are intrinsically critical for normal hematopoiesis but are also expressed in stromal cells. Here, STAT5ab knockout (KO) was generated with a variety of bone marrow hematopoietic and stromal Cre transgenic mouse strains. Vav1-Cre, the positive control for loss of multipotent hematopoietic function, surprisingly dysregulated niche factor mRNA expression and deleted STAT5ab in CD45neg cells. Single cell transcriptome analysis of bone marrow from wild-type or Vav1-Cre KO mice showed hematopoietic stem cell myeloid commitment priming and upregulated protein translation genes. Nes+ cells were detected in both CD45neg and CD45+ clusters and deletion of STAT5ab with Nes-Cre caused hematopoietic repopulating defects. To follow up on these promiscuous Cre promoter deletions in CD45neg and CD45+ bone marrow cell populations, more stroma-specific Cre strains were generated and demonstrated reduction in multipotent hematopoietic progenitors. Functional support for niche-supporting activity was assessed using STAT5-deficient MSCs. With Lepr-Cre, niche factor mRNAs were downregulated by STAT5ab deletion with validation of reduced IGF-1 and CXCL12 proteins. Furthermore, computational analyses (differential expression/co-expression) revealed a key role for STAT5ab/Cish balance with Cish strongly co-expressed in MSCs and HSCs primed for differentiation. Therefore STAT5ab-associated gene regulation supports the bone marrow microenvironment.

A double-beam acousto-optic time-integrating correlator is described that is a modification of a recently reported acousto-optic interferometer. The instrument uses a pair of Kosters double-image prisms and two tellurium dioxide Bragg cells to produce the correlation function of pulsed radio signals.

Objectives:Nursing home residents with dementia are sensitive to detrimental auditory environments. This paper presents the first literature review of empirical research investigating (1) the (perceived) intensity and sources of sounds in nursing homes, and (2) the influence of sounds on health of residents with dementia and staff.Design:A systematic review was conducted in PubMed, Web of Science and Scopus. Study quality was assessed with the Mixed Methods Appraisal Tool. We used a narrative approach to present the results.Results:We included 35 studies. Nine studies investigated sound intensity and reported high noise intensity with an average of 55–68 dB(A) (during daytime). In four studies about sound sources, human voices and electronic devices were the most dominant sources. Five cross-sectional studies focused on music interventions and reported positives effects on agitated behaviors. Four randomized controlled trials tested noise reduction as part of an intervention. In two studies, high-intensity sounds were associated with decreased nighttime sleep and increased agitation. The third study found an association between music and less agitation compared to other stimuli. The fourth study did not find an effect of noise on agitation. Two studies reported that a noisy environment had negative effects on staff.Conclusions:The need for appropriate auditory environments that are responsive to residents’ cognitive abilities and functioning is not yet recognized widely. Future research needs to place greater emphasis on intervention-based and longitudinal study design.