A survey of a population-based sample of U.S adults was conducted to measure their attitudes about, and inform the design of the Precision Medicine Initiative's planned national cohort study.
An ...online survey was conducted by GfK between May and June of 2015. The influence of different consent models on willingness to share data was examined by randomizing participants to one of eight consent scenarios.
Of 4,777 people invited to take the survey, 2,706 responded and 2,601 (54% response rate) provided valid responses. Most respondents (79%) supported the proposed study, and 54% said they would definitely or probably participate if asked. Support for and willingness to participate in the study varied little among demographic groups; younger respondents, LGBT respondents, and those with more years of education were significantly more likely to take part if asked. The most important study incentive that the survey asked about was learning about one's own health information. Willingness to share data and samples under broad, study-by-study, menu and dynamic consent models was similar when a statement about transparency was included in the consent scenarios. Respondents were generally interested in taking part in several governance functions of the cohort study.
A large majority of the U.S. adults who responded to the survey supported a large national cohort study. Levels of support for the study and willingness to participate were both consistent across most demographic groups. The opportunity to learn health information about one's self from the study appears to be a strong motivation to participate.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human memory B cells comprise isotype-switched and nonswitched cells with both subsets displaying somatic hypermutation. In addition to somatic hypermutation, CD27 expression has also been considered ...a universal memory B cell marker. We describe a new population of memory B cells containing isotype-switched (IgG and IgA) and IgM-only cells and lacking expression of CD27 and IgD. These cells are present in peripheral blood and tonsils of healthy subjects and display a degree of hypermutation comparable to CD27+ nonswitched memory cells. As conventional memory cells, they proliferate in response to CpG DNA and fail to extrude rhodamine. In contrast to other recently described CD27-negative (CD27neg) memory B cells, they lack expression of FcRH4 and recirculate in the peripheral blood. Although CD27neg memory cells are relatively scarce in healthy subjects, they are substantially increased in systemic lupus erythematosus (SLE) patients in whom they frequently represent a large fraction of all memory B cells. Yet, their frequency is normal in patients with rheumatoid arthritis or chronic hepatitis C. In SLE, an increased frequency of CD27neg memory cells is significantly associated with higher disease activity index, a history of nephritis, and disease-specific autoantibodies (anti-dsDNA, anti-Smith (Sm), anti-ribonucleoprotein (RNP), and 9G4). These findings enhance our understanding of the B cell diversification pathways and provide mechanistic insight into the immunopathogenesis of SLE.
Rheumatoid arthritis (RA) is mediated by a proinflammatory cytokine network with TNF at its apex. Accordingly, drugs that block TNF have demonstrated significant efficacy in the treatment of RA. A ...great deal of experimental evidence also strongly implicates B cells in the pathogenesis of RA. Yet, it remains unclear whether these two important players and the therapies that target them are mechanistically linked. In this study we demonstrate that RA patients on anti-TNF (etanercept) display a paucity of follicular dendritic cell networks and germinal center (GC) structures accompanied by a reduction in CD38+ GC B cells and peripheral blood memory B cell lymphopenia compared with healthy controls and RA patients on methotrexate. This study provides initial evidence in humans to support the notion that anti-TNF treatment disrupts GC reactions at least in part via effects on follicular dendritic cells.
Foot strike pattern and movement variability have each been associated with running injuries. Foot contact angle (FCA) is a common measure of strike pattern. Thus, variability in FCA could be an ...important running injury risk factor. The purposes of this study were to compare (a) foot contact angle (FCA) and its variability between runners with and without injury history and, (b) FCA variability between habitual rearfoot strike (RFS) and non‐RFS runners during a prolonged run. Twenty‐three runners with and 21 without injury history participated. Motion capture was used to collect kinematic data during a 40 min treadmill run. Average FCA and its variability were compared between injury groups and among four time points. FCA and its variability were not different between runners with and without injury history or among time points during the run. FCA variability was lower in non‐RFS compared to RFS runners (P < 0.001). Lower FCA variability in non‐RFS runners may have implications for higher injury risks due to repeated localized tissue loading. Prospective analyses on the effects of lower FCA variability on injury risk are needed.
Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions ...made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb.
Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity.
The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Interest in hereditary lung cancer is increasing, in particular germline mutations in the Epidermal Growth Factor Receptor (EGFR) gene. We review the current literature on this topic, discuss risk of ...developing lung cancer, treatment and screening options and describe a family of 3 sisters with lung cancer and their unaffected mother all with a rare EGFR germline mutation (EGFR p.R776H).
We searched PubMed, Medline, Embase, the Cochrane Library, Google Scholar and scanned reference lists of articles. Search terms included “EGFR germline” and “familial lung cancer” or “EGFR familial lung cancer”. We also describe our experience of managing a family with rare germline EGFR mutant lung cancer.
Although the numbers are small, the described cases in the literature show several similarities. The patients are younger and usually have no or light smoking history. 50% of the patients were treated with a tyrosine kinase inhibitor (TKIs) with OS over six months.
Although rare, germline p.R776H EGFR lung cancer mutations are over-represented in light or never smoking female patients who often also possess an additional somatic EGFR mutation. Treatment with TKIs appears suitable but further research is needed into the appropriate screening regime for unaffected carriers or light/never smokers.
Basal iguanodontian dinosaurs were extremely successful animals, found in great abundance and diversity almost worldwide during the Early Cretaceous. In contrast to Europe and Asia, the North ...American record of Early Cretaceous basal iguanodonts has until recently been limited largely to skulls and skeletons of Tenontosaurus tilletti.
Herein we describe two new basal iguanodonts from the Yellow Cat Member of the Cedar Mountain Formation of eastern Utah, each known from a partial skull and skeleton. Iguanacolossus fortis gen. et sp. nov. and Hippodraco scutodens gen. et sp. nov. are each diagnosed by a single autapomorphy and a unique combination of characters.
Iguanacolossus and Hippodraco add greatly to our knowledge of North American basal iguanodonts and prompt a new comprehensive phylogenetic analysis of basal iguanodont relationships. This analysis indicates that North American Early Cretaceous basal iguanodonts are more basal than their contemporaries in Europe and Asia.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With rapid urban expansion, biodiversity conservation and human asset protection often require different regimes for managing wildfire risk. We conducted a controlled, replicated experiment to ...optimise habitat restoration for the threatened Australian pink-tailed worm-lizard, Aprasia parapulchella while reducing fire fuel load in a rapidly developing urban area. We used dense addition of natural rock (30Â % cover) and native grass revegetation (Themeda triandra and Poa sieberiana) to restore critical habitat elements. Combinations of fire and herbicide (Glyphosate) were used to reduce fuel load and invasive exotic species. Rock restoration combined with herbicide application met the widest range of restoration goals: it reduced fire fuel load, increased ant occurrence (the primary prey of A. parapulchella) in the short-term and increased the growth and survival of native grasses. Lizards colonised the restored habitat within a year of treatment. Our study documents an innovative way by which conflicts between biodiversity conservation and human asset protection can be overcome.
Extinct animal behavior has often been inferred from qualitative assessments of relative brain region size in fossil endocranial casts. For instance, flight capability in pterosaurs and early birds ...has been inferred from the relative size of the cerebellar flocculus, which in life protrudes from the lateral surface of the cerebellum. A primary role of the flocculus is to integrate sensory information about head rotation and translation to stabilize visual gaze via the vestibulo-occular reflex (VOR). Because gaze stabilization is a critical aspect of flight, some authors have suggested that the flocculus is enlarged in flying species. Whether this can be further extended to a floccular expansion in highly maneuverable flying species or floccular reduction in flightless species is unknown. Here, we used micro computed-tomography to reconstruct "virtual" endocranial casts of 60 extant bird species, to extract the same level of anatomical information offered by fossils. Volumes of the floccular fossa and entire brain cavity were measured and these values correlated with four indices of flying behavior. Although a weak positive relationship was found between floccular fossa size and brachial index, no significant relationship was found between floccular fossa size and any other flight mode classification. These findings could be the result of the bony endocranium inaccurately reflecting the size of the neural flocculus, but might also reflect the importance of the flocculus for all modes of locomotion in birds. We therefore conclude that the relative size of the flocculus of endocranial casts is an unreliable predictor of locomotor behavior in extinct birds, and probably also pterosaurs and non-avian dinosaurs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The literature surrounding rodent models of human anxiety disorders is discrepant concerning which models reflect anxiety‐like behavior distinct from general activity and whether different models are ...measuring the same underlying constructs. This experiment compared the responses of 15 inbred mouse strains (129S1/SvlmJ, A/J, AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, C57L/J, CBA/J, CE/J, DBA/2J, FVB/NJ, NZB/B1NJ, PL/J, SJL/J and SWR/J) in three anxiety‐like behavioral tasks (light/dark test, elevated zero‐maze and open field) to examine whether responses were phenotypically and/or genetically correlated across tasks. Significant strain differences were found for all variables examined. Principal components analyses showed that variables associated with both activity and anxiety‐like behaviors loaded onto one factor, while urination and defecation loaded onto another factor. Our findings differ from previous research by suggesting that general activity and anxiety‐related behaviors are linked, negatively correlated and cannot easily be dissociated in these assays. However, these findings may not necessarily generalize to other unconditioned anxiety‐like behavioral tests.
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