Synthetic C18O observations of fibrous filaments: the problems of mapping from PPV to PPP

Molecular-line observations of filaments in star-forming regions have revealed the existence of elongated coherent features within the filaments; these features are termed fibres. Here we caution that, since fibres are traced in PPV space, there is no guarantee that they represent coherent features in PPP space. We illustrate this contention using simulations of the growth of a filament from a turbulent medium. Synthetic C$^{18}$O observations of the simulated filaments reveal the existence of fibres very similar to the observed ones, i.e. elongated coherent features in the resulting PPV data-cubes. Analysis of the PPP data-cubes (i.e. 3D density fields) also reveals elongated coherent features, which we term sub-filaments. Unfortunately there is very poor correspondence between the fibres and the sub-filaments in the simulations. Both fibres and sub-filaments derive from inhomogeneities in the turbulent accretion flow onto the main filament. As a consequence, fibres are often affected by line-of-sight confusion. Similarly, sub-filaments are often affected by large velocity gradients, and even velocity discontinuities. These results suggest that extreme care should be taken when using velocity coherent features to constrain the underlying substructure within a filament.Comment: 15 pages + appendices, 26 figures. Accepted to MNRA

Resident Memory T Cells (TRM) Are Abundant in Human Lung: Diversity, Function, and Antigen Specificity

Recent studies have shown that tissue resident memory T cells (TRM) are critical to antiviral host defense in peripheral tissues. This new appreciation of TRM that reside in epithelial tissues and mediate host defense has been studied most extensively in skin: adult human skin contains large numbers of functional TRM that express skin specific markers. Indeed, more than twice as many T cells reside in skin as in peripheral blood. This T cell population has a diverse T cell receptor repertoire, and can produce a broad array of cytokines. More recently, we have begun to examine other epithelial tissues for the presence of resident T cells. In the present study, we asked whether analogous populations of resident T cells could be found in human lung. We were able to demonstrate abundant resident T cells in human lung-more than 10 billion T cells were present. Lung T cells were largely of the effector memory T cell (TEM) phenotype, though small numbers of central memory T cells (TCM) and T regulatory cells (Treg) could be identified. Lung T cells had a diverse T cell receptor repertoire and subsets produced IL-17, IL-4, IFNγ, as well as TNFα. A significant number of lung TRM CD4+Th cells produced more than one cytokine, identifying them as “multifunctional” Th1 type cells. Finally, lung TRM, but not TRM resident to skin or T cells from blood, proliferated in response to influenza virus. This work suggests that normal human lung contains large numbers of TRM cells, and these cells are poised to respond to recall antigens previously encountered through lung mucosa. This population of T cells may contribute to the pathogenesis of asthma and other T cell mediated lung diseases

Patients’ Experiences of a Sarcoma Diagnosis: A Process Mapping Exercise of Diagnostic Pathways

Patients with sarcoma often report prolonged time to diagnosis, which is attributed to the rarity of sarcoma and the low awareness of pre-diagnostic signs and symptoms. Aims: To describe patients’ experiences of pre-diagnostic signs/symptoms and pathways to diagnosis, including where help was sought, and the processes involved. Methods: Mixed methods involving quantitative, qualitative and inductive thematic analyses using novel process mapping of patient journey data, as reported by the patients. We examined the time from symptom onset to first professional presentation (patient interval, PI), first consultation to diagnostic biopsy, first consultation to diagnosis (diagnostic interval) and first presentation to diagnosis (total interval). Results: A total of 87 interviews were conducted over 5 months in 2017. Of these, 78 (40 males/38 females) were included. The sarcoma subtypes were bone (n = 21), soft tissue (n = 41), head and neck (n = 9) and gastro-intestinal (GIST; n = 7). Age at diagnosis was 13–24 (n = 7), 25–39 (n = 23), 40–64 (n = 34) and 65+ (n = 14) years. The median PI was 13 days (1–4971) and similar between sarcoma subtypes, with the exception of GIST (mPI = 2 days, (1–60). The longest mPI (31 days, range 4–762) was for those aged 13–24 years. The median diagnostic interval was 87.5 (range 0–5474 days). A total of 21 patients were misdiagnosed prior to diagnosis and symptoms were commonly attributed to lifestyle factors. Conclusions: Prolonged times to diagnosis were experienced by the majority of patients in our sample. Further research into the evolution of pre-diagnostic sarcoma symptoms is required to inform awareness interventions

Ecological correlates of risk and incidence of West Nile virus in the United States

West Nile virus, which was recently introduced to North America, is a mosquito-borne pathogen that infects a wide range of vertebrate hosts, including humans. Several species of birds appear to be the primary reservoir hosts, whereas other bird species, as well as other vertebrate species, can be infected but are less competent reservoirs. One hypothesis regarding the transmission dynamics of West Nile virus suggests that high bird diversity reduces West Nile virus transmission because mosquito blood-meals are distributed across a wide range of bird species, many of which have low reservoir competence. One mechanism by which this hypothesis can operate is that high-diversity bird communities might have lower community-competence, defined as the sum of the product of each species’ abundance and its reservoir competence index value. Additional hypotheses posit that West Nile virus transmission will be reduced when either: (1) abundance of mosquito vectors is low; or (2) human population density is low. We assessed these hypotheses at two spatial scales: a regional scale near Saint Louis, MO, and a national scale (continental USA). We found that prevalence of West Nile virus infection in mosquito vectors and in humans increased with decreasing bird diversity and with increasing reservoir competence of the bird community. Our results suggest that conservation of avian diversity might help ameliorate the current West Nile virus epidemic in the USA

Diagnosing Norms Surrounding Sexual Harassment at a Jordanian University

Sexual harassment (SH) is a form of gender-based violence (GBV) that negatively impacts women’s physical, mental, social, and financial well-being. Although SH is a global phenomenon, it also is a contextualized one, with local and institutional norms influencing the ways in which harassment behavior manifests. As more women attend institutions of higher education in Jordan, these women are at increased risk of experiencing SH in university settings, with potential implications for their health and future employment. Social norms theory, which examines the informal rules governing individual behavior within groups, has been a useful framework for understanding and developing interventions against GBV globally. We sought to apply a social-norms lens to the understanding and prevention of SH at a Jordanian university. To gain a comprehensive and nuanced picture of social norms surrounding SH, we collected qualitative data using three complementary methods: focus group discussions (n = 6) with male and female students (n = 33); key informant interviews with staff and faculty (n = 5); and a public, participatory event to elicit anonymous short responses from students (n = 317). Using this data, we created a codebook incorporating social-norms components and emergent themes. As perceived by participants, SH was unacceptable yet common, characterized as a weak norm primarily because negative sanctioning of harassers was unlikely. Distal norms related to gender and tribal affiliation served to weaken further norms against SH by blaming the victim, preventing reporting, discouraging bystander intervention, and/or protecting the perpetrator. The complexity of the normative environment surrounding SH perpetration will necessitate the use of targeted, parallel approaches to change harmful norms. Strengthening weak norms against SH will require increasing the likelihood of sanctions, by revising university policies and procedures to increase accountability, increasing the acceptability of bystander intervention and reporting, and fostering tribal investment in sanctioning members who harass women. Creating dialogue that emphasizes the harmful nature of SH behaviors and safe spaces to practice positive masculinity also may be an effective strategy to change how male students interact in the presence of peers. Any social norms change intervention will need to consider the various reference groups that dictate and enforce norms surrounding SH

CD1a selectively captures endogenous cellular lipids that broadly block T cell response

We optimized lipidomics methods to broadly detect endogenous lipids bound to cellular CD1a proteins. Whereas membrane phospholipids dominate in cells, CD1a preferentially captured sphingolipids, especially a C42, doubly unsaturated sphingomyelin (42:2 SM). The natural 42:2 SM but not the more common 34:1 SM blocked CD1a tetramer binding to T cells in all human subjects tested. Thus, cellular CD1a selectively captures a particular endogenous lipid that broadly blocks its binding to TCRs. Crystal structures show that the short cellular SMs stabilized a triad of surface residues to remain flush with CD1a, but the longer lipids forced the phosphocholine group to ride above the display platform to hinder TCR approach. Whereas nearly all models emphasize antigen-mediated T cell activation, we propose that the CD1a system has intrinsic autoreactivity and is negatively regulated by natural endogenous inhibitors selectively bound in its cleft. Further, the detailed chemical structures of natural blockers could guide future design of therapeutic blockers of CD1a response

Oxygen- and capacity-limited thermal tolerance: blurring ecology and physiology

No abstract available

White matter predicts functional connectivity in premanifest Huntington's disease

Objectives The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and function is critical for understanding how underlying brain pathology influences the progressive behavioral changes associated with neurodegeneration. Here, we demonstrate such a link between structure and function in individuals with premanifest Huntington's. Methods Using diffusion tractography and resting state functional magnetic resonance imaging to characterize white matter organization and functional connectivity, we investigate whether characteristic patterns of white matter organization in the healthy human brain shape the changes in functional coupling between brain regions in premanifest Huntington's disease. Results We find changes in functional connectivity in premanifest Huntington's disease that link directly to underlying patterns of white matter organization in healthy brains. Specifically, brain areas with strong structural connectivity show decreases in functional connectivity in premanifest Huntington's disease relative to controls, while regions with weak structural connectivity show increases in functional connectivity. Furthermore, we identify a pattern of dissociation in the strongest functional connections between anterior and posterior brain regions such that anterior functional connectivity increases in strength in premanifest Huntington's disease, while posterior functional connectivity decreases. Interpretation Our findings demonstrate that organizational principles of white matter underlie changes in functional connectivity in premanifest Huntington's disease. Furthermore, we demonstrate functional antero–posterior dissociation that is in keeping with the caudo–rostral gradient of striatal pathology in HD. The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and function is critical for understanding how underlying brain pathology influences the progressive behavioral changes associated with neurodegeneration. Here, we demonstrate such a link between structure and function in individuals with premanifest Huntington's. Methods Using diffusion tractography and resting state functional magnetic resonance imaging to characterize white matter organization and functional connectivity, we investigate whether characteristic patterns of white matter organization in the healthy human brain shape the changes in functional coupling between brain regions in premanifest Huntington's disease. Results We find changes in functional connectivity in premanifest Huntington's disease that link directly to underlying patterns of white matter organization in healthy brains. Specifically, brain areas with strong structural connectivity show decreases in functional connectivity in premanifest Huntington's disease relative to controls, while regions with weak structural connectivity show increases in functional connectivity. Furthermore, we identify a pattern of dissociation in the strongest functional connections between anterior and posterior brain regions such that anterior functional connectivity increases in strength in premanifest Huntington's disease, while posterior functional connectivity decreases. Interpretation Our findings demonstrate that organizational principles of white matter underlie changes in functional connectivity in premanifest Huntington's disease. Furthermore, we demonstrate functional antero–posterior dissociation that is in keeping with the caudo–rostral gradient of striatal pathology in HD