49 research outputs found

    The Ill Man: An Exploration of Chronic Illness Disclosure within Masculine Culture

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    Masculine culture is known for teaching men to be strong, independent, and in control; however, the presence of chronic illness creates challenges for men when attempting to uphold a dominant masculine identity and make disclosure decisions about sharing illness information. This study explores the intersection between illness related self-disclosure and masculine culture. Utilizing qualitative methods, it examines the challenges chronically ill men face when making decisions about self-disclosure. Semi-structured interviews were conducted with five men (N=5) who have one or more chronic illnesses. Transcripts were analyzed and coded using grounded theory to identify emergent themes. The analysis revealed three primary themes and several secondary and tertiary themes. The three primary themes are: 1) participant expression of masculine culture; 2) communication challenges; and 3) disclosure strategies. Participants’ accounts of their experiences with living with chronic illness are positioned within literature on chronic illnesses, self-disclosure, and masculine culture

    Unsupervised Content-Based Characterization and Anomaly Detection of Online Community Dynamics

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    The structure and behavior of human networks have been investigated and quantitatively modeled by modern social scientists for decades, however the scope of these efforts is often constrained by the labor-intensive curation processes that are required to collect, organize, and analyze network data. The surge in online social media in recent years provides a new source of dynamic, semi-structured data of digital human networks, many of which embody attributes of real-world networks. In this paper we leverage the Reddit social media platform to study social communities whose dynamics indicate they may have experienced a disturbance event. We describe an unsupervised approach to analyzing natural language content for quantifying community similarity, monitoring temporal changes, and detecting anomalies indicative of disturbance events. We demonstrate how this method is able to detect anomalies in a spectrum of Reddit communities and discuss its applicability to unsupervised event detection for a broader class of social media use cases

    The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

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    Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

    Anterolateral Ligament Expert Group consensus paper on the management of internal rotation and instability of the anterior cruciate ligament - deficient knee

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    Purpose of this paper is to provide an overview of the latest research on the anterolateral ligament (ALL) and present the consensus of the ALL Expert Group on the anatomy, radiographic landmarks, biomechanics, clinical and radiographic diagnosis, lesion classification, surgical technique and clinical outcomes. A consensus on controversial subjects surrounding the ALL and anterolateral knee instability has been established based on the opinion of experts, the latest publications on the subject and an exchange of experiences during the ALL Experts Meeting (November 2015, Lyon, France). The ALL is found deep to the iliotibial band. The femoral origin is just posterior and proximal to the lateral epicondyle; the tibial attachment is 21.6 mm posterior to Gerdy's tubercle and 4-10 mm below the tibial joint line. On a lateral radiographic view the femoral origin is located in the postero-inferior quadrant and the tibial attachment is close to the centre of the proximal tibial plateau. Favourable isometry of an ALL reconstruction is seen when the femoral position is proximal and posterior to the lateral epicondyle, with the ALL being tight upon extension and lax upon flexion. The ALL can be visualised on ultrasound, or on T2-weighted coronal MRI scans with proton density fat-suppressed evaluation. The ALL injury is associated with a Segond fracture, and often occurs in conjunction with acute anterior cruciate ligament (ACL) injury. Recognition and repair of the ALL lesions should be considered to improve the control of rotational stability provided by ACL reconstruction. For high-risk patients, a combined ACL and ALL reconstruction improves rotational control and reduces the rate of re-rupture, without increased postoperative complication rates compared to ACL-only reconstruction. In conclusion this paper provides a contemporary consensus on all studied features of the ALL. The findings warrant future research in order to further test these early observations, with the ultimate goal of improving the long-term outcomes of ACL-injured patients. Level of evidence Level V-Expert opinion

    Sensory and Quasi-Sensory Experiences of the Deceased in Bereavement : An Interdisciplinary and Integrative Review

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    Bereaved people often report having sensory and quasi-sensory experiences of the deceased (SED), and there is an ongoing debate over whether SED are associated with pathology, such as grief complications. Research into these experiences has been conducted in various disciplines, including psychiatry, psychology, and anthropology, without much crossover. This review brings these areas of research together, drawing on the expertise of an interdisciplinary working group formed as part of the International Consortium for Hallucination Research (ICHR). It examines existing evidence on the phenomenology, associated factors, and impact of SED, including the role of culture, and discusses the main theories on SED and how these phenomena compare with unusual experiences in other contexts. The review concludes that the vast majority of these experiences are benign and that they should be considered in light of their biographical, relational, and sociocultural contexts

    Validating Molecular Dynamics Simulations against Experimental Observables in Light of Underlying Conformational Ensembles

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    Far from the static, idealized conformations deposited into structural databases, proteins are highly dynamic molecules that undergo conformational changes on temporal and spatial scales that may span several orders of magnitude. These conformational changes, often intimately connected to the functional roles that proteins play, may be obscured by traditional biophysical techniques. Over the past 40 years, molecular dynamics (MD) simulations have complemented these techniques by providing the “hidden” atomistic details that underlie protein dynamics. However, there are limitations of the degree to which molecular simulations accurately and quantitatively describe protein motions. Here we show that although four molecular dynamics simulation packages (AMBER, GROMACS, NAMD, and <i>il</i>mm) reproduced a variety of experimental observables for two different proteins (engrailed homeodomain and RNase H) equally well overall at room temperature, there were subtle differences in the underlying conformational distributions and the extent of conformational sampling obtained. This leads to ambiguity about which results are correct, as experiment cannot always provide the necessary detailed information to distinguish between the underlying conformational ensembles. However, the results with different packages diverged more when considering larger amplitude motion, for example, the thermal unfolding process and conformational states sampled, with some packages failing to allow the protein to unfold at high temperature or providing results at odds with experiment. While most differences between MD simulations performed with different packages are attributed to the force fields themselves, there are many other factors that influence the outcome, including the water model, algorithms that constrain motion, how atomic interactions are handled, and the simulation ensemble employed. Here four different MD packages were tested each using best practices as established by the developers, utilizing three different protein force fields and three different water models. Differences between the simulated protein behavior using two different packages but the same force field, as well as two different packages with different force fields but the same water models and approaches to restraining motion, show how other factors can influence the behavior, and it is incorrect to place all the blame for deviations and errors on force fields or to expect improvements in force fields alone to solve such problems

    Validating Molecular Dynamics Simulations against Experimental Observables in Light of Underlying Conformational Ensembles

    No full text
    Far from the static, idealized conformations deposited into structural databases, proteins are highly dynamic molecules that undergo conformational changes on temporal and spatial scales that may span several orders of magnitude. These conformational changes, often intimately connected to the functional roles that proteins play, may be obscured by traditional biophysical techniques. Over the past 40 years, molecular dynamics (MD) simulations have complemented these techniques by providing the “hidden” atomistic details that underlie protein dynamics. However, there are limitations of the degree to which molecular simulations accurately and quantitatively describe protein motions. Here we show that although four molecular dynamics simulation packages (AMBER, GROMACS, NAMD, and <i>il</i>mm) reproduced a variety of experimental observables for two different proteins (engrailed homeodomain and RNase H) equally well overall at room temperature, there were subtle differences in the underlying conformational distributions and the extent of conformational sampling obtained. This leads to ambiguity about which results are correct, as experiment cannot always provide the necessary detailed information to distinguish between the underlying conformational ensembles. However, the results with different packages diverged more when considering larger amplitude motion, for example, the thermal unfolding process and conformational states sampled, with some packages failing to allow the protein to unfold at high temperature or providing results at odds with experiment. While most differences between MD simulations performed with different packages are attributed to the force fields themselves, there are many other factors that influence the outcome, including the water model, algorithms that constrain motion, how atomic interactions are handled, and the simulation ensemble employed. Here four different MD packages were tested each using best practices as established by the developers, utilizing three different protein force fields and three different water models. Differences between the simulated protein behavior using two different packages but the same force field, as well as two different packages with different force fields but the same water models and approaches to restraining motion, show how other factors can influence the behavior, and it is incorrect to place all the blame for deviations and errors on force fields or to expect improvements in force fields alone to solve such problems

    Modulation of post-powerstroke dynamics in myosin II by 2′-deoxy-ADP

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    Muscle myosins are molecular motors that hydrolyze ATP and generate force through coordinated interactions with actin filaments, known as cross-bridge cycling. During the cross-bridge cycle, functional sites in myosin ‘sense’ changes in interactions with actin filaments and the nucleotide binding region, resulting in allosteric transmission of information throughout the structure. We investigated whether the dynamics of the post- powerstroke state of the cross-bridge cycle are modulated in a nucleotide-dependent fashion. We compared molecular dynamics simulations of the myosin II motor domain (M) from Dictyostelium discoideum in the presence of ADP (M.ADP) versus 2′-deoxy-ADP bound myosin (M.dADP). We found that dADP was more flexible than ADP and the two nucleotides interacted with myosin in different ways. Replacement of ADP with dADP in the post- powerstroke state also altered the conformation of the actin binding region in myosin heads. Our results provide atomic level insights into allosteric communication networks in myosin that provide insight into the nucleotide- dependent dynamics of the cross-bridge cycle
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