84 research outputs found
Interpreting Community Accountability: Citizen Views of Responding to Domestic Violence (or Not)
In spite of common public condemnations of domestic violence, survey research suggests that citizens aware of actual abuse often believe they cannot or should not personally respond. Through in-depth interviews with 20 local citizens across the political spectrum, we sought to explore this dynamic more carefully by better understanding community interpretations of domestic violence and its appropriate response. This paper explores ten specific views identified in these interviews as potentially relevant to citizen action (or inaction) in response to known abuse. After examining subtle consequences of each belief, we explore broader implications for community mobilization and propose several ways of facilitating a more thoughtful and extensive deliberation about domestic violence among the general public
Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents
BACKGROUND: HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%≥25 were categorized as having no immune suppression (NS), and those with CD4%≤15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLA- B*57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of naïve CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups. CONCLUSIONS/SIGNIFICANCE: Together, these data suggest that, at least in vertically infected adolescents, the region of HIV-1-Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions
A hierarchy of determining factors controls motoneuron innervation
Quail leg buds were grafted in place of chick leg buds or chick wing buds and vice versa at stages 18 to 21 after colonization by muscle precursor cells had been completed. Motor endplate pattern in the plantaris muscle of the grafts was analyzed before hatching by means of esterase and acetylcholinesterase staining techniques. Muscle fibre types were made visual using the myosin ATPase reaction. Investigations are based on the species-specific endplate pattern of the plantaris muscle: multiply innervated fibres in the chick and focally innervated fibres in the quail. Muscle pieces isolated from the adjacent medial gastrocnemius muscle of the grafted legs were histologically examined to judge their species-specific composition. Horseradish peroxidase was injected into the plantaris muscles of both the grafted and the opposite leg as well as in the plantaris muscle of normal quail embryos, in order to be sure that the plantaris muscle of the graft is innervated by appropriate motoneurons. This procedural design offers for the first time a possibility to test experimentally the influences of motoneurons on endplate pattern formation under conditions corresponding to those in normal ontogenesis. It is shown that such appropriate motoneurons of one species which project to the plantaris muscle of the other species dictate the endplate pattern. When the plantaris muscle is innervated by inappropriate motoneurons, the endplate pattern inherent in the muscle primordium itself becomes realized. A sequence of hierarchically acting factors is proposed to bring different results in line. According to this, the neuronally set programme has priority compared with that set in the muscle. This is true for the normal development and might generate the high neuro-muscular specificity. If under experimental conditions the neuronal programme and the peripheral programme differ, the axons and muscle fibres selectively interact with respect to their inherent characteristics and the muscle-specific programme becomes expressed. If there is a lack of a certain axon type, muscle fibres might become innervated by non-corresponding motoneurons which alter the muscle fibre type.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47522/1/429_2004_Article_BF00309770.pd
Detection of extended TeV emission around the Geminga pulsar with H.E.S.S.
Highly extended gamma-ray emission around the Geminga pulsar was discovered by Milagro and verified by HAWC. Despite many observations with Imaging Atmospheric Cherenkov Telescopes (IACTs), detection of gamma-ray emission on angular scales exceeding the IACT field-of-view has proven challenging. Recent developments in analysis techniques have enabled the detection of significant emission around Geminga in archival data with H.E.S.S.. In 2019, further data on the Geminga region were obtained with an adapted observation strategy. Following the announcement of the detection of significant TeV emission around Geminga in archival data, in this contribution we present the detection in an independent dataset. New analysis results will be presented, and emphasis given to the technical challenges involved in observations of highly extended gamma-ray emission with IACTs
Search for enhanced TeV gamma ray emission from Giant Molecular Clouds using H.E.S.S.
Cosmic Ray (CR) interactions with the dense gas inside Giant Molecular Clouds (GMCs) produce neutral pions, which in turn decay into gamma rays. Thus, the gamma ray emission from GMCs is a direct tracer of the cosmic ray density and the matter density inside the clouds. Detection of enhanced TeV emission from GMCs, i.e., an emission significantly larger than what is expected from the average Galactic cosmic rays illuminating the cloud, can imply a variation in the local cosmic ray density, due to, for example, the presence of a recent accelerator in proximity to the cloud. Such gamma-ray observations can be crucial in probing the cosmic ray distribution across our Galaxy, but are complicated to perform with present generation Imaging Atmospheric Cherenkov Telescopes (IACTs). These studies require differentiating between the strong cosmic-ray induced background, the large scale diffuse emission, and the emission from the clouds, which is difficult to the small field of view of present generation IACTs. In this contribution, we use H.E.S.S. data collected over 16 years to search for TeV emission from GMCs in the inner molecular galacto-centric ring of our Galaxy. We implement a 3D FoV likelihood technique, and simultaneously model the hadronic background, the galactic diffuse emission and the emission expected from known VHE sources to probe for excess TeV gamma ray emission from GMCs
Multi-messenger observations of a binary neutron star merger
On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
"Prozac Saved My Life" vs. "Prozac Ruined My Life": Investigating the Adoption, Constitution and Maintenance of Distinct Interpretations Associated with Depression and its Medical Treatment.
Beyond the brute pain of depression, individuals enduring this problem also commonly face a more subtle, added burden related to both societal and personal confusion about the basic nature of depression and its appropriate resolution. This dissertation study seeks to better understand diverging interpretations or narratives at play in the experiences of those facing depression by examining the language of actual survivors. In particular, the complexity of individuals’ decisions regarding possible medication use is investigated. Through fourteen in-depth interviews with survivors reflecting diverse (both positive and negative) psychiatric experiences, three specific questions are explored: 1) How exactly do individuals come to adopt a particular narrative of depression and its treatment? 2) What are the most meaningful differences between varied narratives that arise? 3) After being adopted, how do particular narratives appear to be maintained over time? The first section of the report describes basic patterns across survivor accounts—first, in reviewing individual synopses of each narrative (Ch. 3), and second, in documenting key interpretive themes across all interviews (Ch. 4-5). The second section moves into more direct analyses of these narratives, taking up explicitly the three empirical questions in turn. Chapter 6 identifies multiple resources that individuals draw upon in the adoption of distinct treatment narratives (e.g., intense levels of confusion and urgency; comments from friends/family; drug effects). Ensuing moments are proposed as powerfully cementing and galvanizing specific interpretations of both depression and associated medication use. Chapter 7 explores several issues underlying some of the most meaningful differences between narratives (how participants interpret the role of biology, agency, medication and surrounding relationships). In Chapter 8, strategies that appear to be associated with the maintenance of particular treatment narratives are examined. Among other things, analysis of patterns across accounts points to a striking role for diverging narratives in the unfolding treatment experiences of those facing depression. Since such individuals typically have little awareness that their treatment experience can be interpreted in fundamentally different ways, nor that these distinctions may have substantial implications for how their experience ultimately unfolds, a more thoughtful and broad-based deliberation involving both professionals and those facing depression is subsequently proposed.unpublishe
"Prozac Saved My Life" vs. "Prozac Ruined My Life": Investigating the Adoption, Constitution and Maintenance of Distinct Interpretations Associated With Depression and Its Medical Treatment
219 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009.Beyond the brute pain of depression, individuals enduring this problem also commonly face a more subtle, added burden related to both societal and personal confusion about the basic nature of depression and its appropriate resolution. This dissertation study seeks to better understand diverging interpretations or narratives at play in the experiences of those facing depression by examining the language of actual survivors. In particular, the complexity of individuals' decisions regarding possible medication use is investigated. Through fourteen in-depth interviews with survivors reflecting diverse (both positive and negative) psychiatric experiences, three specific questions are explored: (1) How exactly do individuals come to adopt a particular narrative of depression and its treatment? (2) What are the most meaningful differences between varied narratives that arise? (3) After being adopted, how do particular narratives appear to be maintained over time? The first section of the report describes basic patterns across survivor accounts---first, in reviewing individual synopses of each narrative (Ch. 3), and second, in documenting key interpretive themes across all interviews (Ch. 4-5). The second section moves into more direct analyses of these narratives, taking up explicitly the three empirical questions in turn. Chapter 6 identifies multiple resources that individuals draw upon in the adoption of distinct treatment narratives (e.g., intense levels of confusion and urgency; comments from friends/family; drug effects). Ensuing moments are proposed as powerfully cementing and galvanizing specific interpretations of both depression and associated medication use. Chapter 7 explores several issues underlying some of the most meaningful differences between narratives (how participants interpret the role of biology, agency, medication and surrounding relationships). In Chapter 8, strategies that appear to be associated with the maintenance of particular treatment narratives are examined. Among other things, analysis of patterns across accounts points to a striking role for diverging narratives in the unfolding treatment experiences of those facing depression. Since such individuals typically have little awareness that their treatment experience can be interpreted in fundamentally different ways---nor that these distinctions may have substantial implications for how their experience ultimately unfolds---a more thoughtful and broad-based deliberation involving both professionals and those facing depression is subsequently proposed.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD
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