492 research outputs found

    Ecology of the Ocean Sunfish, Mola mola, in the southern California Current System

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    The common ocean sunfish, Mola mola, occupies a unique position in the eastern Pacific Ocean and the California Current Large Marine Ecosystem (CCLME) as the world\u27s heaviest, most fecund bony fish, and one of the most abundant gelativores. M. mola frequently occur as bycatch in fisheries worldwide and comprise the greatest portion of the bycatch in California\u27s large-mesh drift gillnet fishery. In this first long-term tagging study of any ocean sunfish species in the eastern Pacific, 15 M. mola (99 cm to 200 cm total length) were tagged in the southern California Bight (SCB) between 2003 and 2010 using 14 satellite pop-off archival tags (PATs) and one Fastloc Mk10 GPS tag. Ten tags provided positional data for a cumulative dataset of 349 tracking days during the months of july through March. Thirteen tags provided temperature and depth data. All M. mola remained within similar to 300 km of the coast, and nearly all exhibited seasonal movement between the SCB and adjacent waters off northern and central Baja California, Mexico. No tagged individuals were tracked north of the SCB. Tag depth data showed diel vertical migration and occasional deep (\u3e500 m) dives. Data from the Fastloc GPS tag allowed close examination of the relationship between the movements of the largest tagged ocean sunfish (2 m TL) and fine-scale oceanographic features. Near-instantaneous satellite sea surface temperature images showed this individual associated with upwelling fronts along its migration path, which exceeded 800 km and ranged from 6 to 128 km from the coast. Tag depth data showed active use of the water column within the frontal zones. Synthetic aperture radar (SAR) images demonstrated that surface slicks, which often indicate convergent circulation, coincided with this type of front. Zooplankton tows in the southern region of tracking off central Baja California, Mexico revealed dense populations of salps toward the warm side of these fronts. Satellite tag and ecosystem data suggest that bio-physical interactions in coastal upwelling fronts create favorable foraging habitat. (C) 2015 The Authors. Published by Elsevier B.V

    Constitutive TRIM22 expression in the respiratory airway confers a pre-existing defence against influenza A virus infection

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    The induction of antiviral effector proteins as part of a homeostatically controlled innate immune response to infection plays a critical role in limiting the propagation and transmission of respiratory pathogens. However, the prolonged induction of this immune response can lead to lung hyperinflammation, tissue damage, and respiratory failure. We hypothesized that tissues exposed to the constant threat of infection may constitutively express higher levels of antiviral effector proteins to reduce the need to activate potentially harmful innate immune defences. By analysing transcriptomic data derived from a range of human tissues, we identify lung tissue to express constitutively higher levels of antiviral effector genes relative to that of other mucosal and non-mucosal tissues. By using primary cell lines and the airways of rhesus macaques, we show the interferon-stimulated antiviral effector protein TRIM22 (TRIpartite Motif 22) to be constitutively expressed in the lung independently of viral infection or innate immune stimulation. These findings contrast with previous reports that have shown TRIM22 expression in laboratory-adapted cell lines to require interferon stimulation. We demonstrate that constitutive levels of TRIM22 are sufficient to inhibit the onset of human and avian influenza A virus (IAV) infection by restricting the onset of viral transcription independently of interferon-mediated innate immune defences. Thus, we identify TRIM22 to confer a pre-existing (intrinsic) intracellular defence against IAV infection in cells derived from the respiratory tract. Our data highlight the importance of tissue-specific and cell-type dependent patterns of pre-existing immune gene expression in the intracellular restriction of IAV from the outset of infection

    Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study.

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    BACKGROUND: Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation. METHODS: This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device. RESULTS: After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training. CONCLUSIONS: The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients

    Constitutive TRIM22 expression within the respiratory tract identifies tissue-specific and cell-type dependent intrinsic immune barriers to influenza A virus infection

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    We hypothesized that increased expression of antiviral host factors at portals of viral entry may protect exposed tissues from the constant threat of invading pathogens. Comparative transcriptomic analysis identified the broad-acting restriction factor TRIM22 (TRIpartite Motif 22) to be among the most abundantly expressed antiviral host factors in the lung, a major portal of entry for many respiratory pathogens. This was surprising, as TRIM22 is currently considered to be an interferon stimulated gene (ISG) product that confers protection following the activation of pathogen-induced cytokine-mediated innate immune defences. Using human respiratory cell lines and the airways of rhesus macaques, we experimentally confirmed high levels of constitutive TRIM22 expression in the lung. In contrast, TRIM22 expression in many widely used transformed cell lines could only be observed following immune stimulation. Endogenous levels of TRIM22 in non-transformed cells were sufficient to restrict human and avian influenza A virus (IAV) infection by inhibiting the onset of viral transcription independently of cytokine-mediated innate immune defences. Thus, TRIM22 confers a pre-existing (intrinsic) tissue-specific immune barrier to IAV infection in the respiratory tract. We investigated whether the constitutive expression of TRIM22 was a characteristic shared by other ISGs in human lung tissue. Transcriptomic analysis identified a large group of ISGs and IAV immuno-regulatory host factors that were similarly enriched in the lung relative to other mucosal tissues, but whose expression was downregulated in transformed cell-lines. We identify common networks of immune gene downregulation which correlated with enhanced permissivity of transformed cells to initiate IAV replication. Our data highlight the importance of tissue-specific and cell-type dependent patterns of pre-existing immune gene expression in the intrinsic intracellular restriction of IAV; findings highly relevant to the immune regulation of many clinically important respiratory pathogens

    Probing the Structure, Dynamics, and Bonding of Coinage Metal Complexes of White Phosphorus

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    A series of cationic white phosphorus complexes of the coinage metals Au and Cu have been synthesised and characterised both in the solid state and in solution. All complexes feature a P4 unit coordinated through an edge P-P vector (η(2)-like), although the degree of activation (as measured by the coordinated P-P bond length) is greater in the gold species. All of the cations are fluxional on the NMR timescale at room temperature, but in the case of the gold systems fluxionality is frozen out at -90 °C. Electronic structure calculations suggest that this fluxionality proceeds via an η(1)-coordinated M-P4 intermediate

    Gaze-based rehearsal in children under 7:A developmental investigation of eye movements during a serial spatial memory task

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    The emergence of strategic verbal rehearsal at around 7 years of age is widely considered a major milestone in descriptions of the development of short‐term memory across childhood. Likewise, rehearsal is believed by many to be a crucial factor in explaining why memory improves with age. This apparent qualitative shift in mnemonic processes has also been characterized as a shift from passive visual to more active verbal mnemonic strategy use, but no investigation of the development of overt spatial rehearsal has informed this explanation. We measured serial spatial order reconstruction in adults and groups of children 5–7 years old and 8–11 years old, while recording their eye movements. Children, particularly the youngest children, overtly fixated late‐list spatial positions longer than adults, suggesting that younger children are less likely to engage in covert rehearsal during stimulus presentation than older children and adults. However, during retention the youngest children overtly fixated more of the to‐be‐remembered sequences than any other group, which is inconsistent with the idea that children do nothing to try to remember. Altogether, these data are inconsistent with the notion that children under 7 do not engage in any attempts to remember. They are most consistent with proposals that children's style of remembering shifts around age 7 from reactive cue‐driven methods to proactive, covert methods, which may include cumulative rehearsal

    Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

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    Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

    What Makes AI ‘Intelligent’ and ‘Caring’?:Exploring Affect and Relationality Across Three Sites of Intelligence and Care

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    This research was funded in whole by the Wellcome Trust [Seed Award ‘AI and Health’ 213643/Z/18/Z]. For the purpose of Open Access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The authors would like to thank Dr Jane Hopton for inspiring discussions about AI and dimensions of intelligence, and three anonymous reviewers as well as the editor in chief Dr Timmemans at Social Science and Medicine for their very helpful and constructive feedback.Peer reviewedPublisher PD
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