56 research outputs found
Toward stronger theory in critical public health: Insights from debates surrounding posthumanism
The “posthumanist turn” in critical theory comprises efforts to recognize and analyze the interdependence of human existence with non-human entities, including other animals, spaces, and technologies. Scholarship aligned to and debating posthumanism pertains to public health, but has yet to be clearly articulated for a public health audience. This commentary and an appended glossary illustrate the relevance of these ideas for enhancing critical theory in public health. Keywords: Social Sciences, Humanities, Technology, Animals, Public HealthCanadian Institutes of Health Researc
Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer
Background
Mesothelin has attracted much interest as a tumor specific antigen; it has been reported to promote tumor development and to be a good target for cancer treatment. Most studies to date have used human mesothelin in immunocompromised mice. Since these models do not allow for study of the natural immune response to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so the effects of this protein can be assessed in immunocompetent mouse strains.
Methods
We analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo.
Results
We show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorage-independent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice.
Conclusion
The mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice
Toward stronger theory in critical public health: insights from debates surrounding posthumanism
The \u27posthumanist turn\u27 in critical theory comprises efforts to recognize and analyze the interdependence of human existence with non-human entities, including other animals, spaces, and technologies. Scholarship aligned to and debating posthumanism pertains to public health, but has yet to be clearly articulated for a public health audience. This commentary and an appended glossary illustrate the relevance of these ideas for enhancing critical theory in public health. 2013 Taylor & Francis
The Zwicky Transient Facility: System Overview, Performance, and First Results
The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg^2 field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope
Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures
Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo
To which world regions does the valence–dominance model of social perception apply?
Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of
how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social
judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether
these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across
11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy,
the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated
dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance
model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed
when we use different extraction methods and correlate and rotate the dimension reduction solution.C.L. was supported by the Vienna Science and Technology Fund (WWTF VRG13-007);
L.M.D. was supported by ERC 647910 (KINSHIP); D.I.B. and N.I. received funding from
CONICET, Argentina; L.K., F.K. and Á. Putz were supported by the European Social
Fund (EFOP-3.6.1.-16-2016-00004; ‘Comprehensive Development for Implementing
Smart Specialization Strategies at the University of Pécs’). K.U. and E. Vergauwe were
supported by a grant from the Swiss National Science Foundation (PZ00P1_154911 to E.
Vergauwe). T.G. is supported by the Social Sciences and Humanities Research Council
of Canada (SSHRC). M.A.V. was supported by grants 2016-T1/SOC-1395 (Comunidad
de Madrid) and PSI2017-85159-P (AEI/FEDER UE). K.B. was supported by a grant
from the National Science Centre, Poland (number 2015/19/D/HS6/00641). J. Bonick
and J.W.L. were supported by the Joep Lange Institute. G.B. was supported by the Slovak
Research and Development Agency (APVV-17-0418). H.I.J. and E.S. were supported
by a French National Research Agency ‘Investissements d’Avenir’ programme grant
(ANR-15-IDEX-02). T.D.G. was supported by an Australian Government Research
Training Program Scholarship. The Raipur Group is thankful to: (1) the University
Grants Commission, New Delhi, India for the research grants received through its
SAP-DRS (Phase-III) scheme sanctioned to the School of Studies in Life Science;
and (2) the Center for Translational Chronobiology at the School of Studies in Life
Science, PRSU, Raipur, India for providing logistical support. K. Ask was supported by
a small grant from the Department of Psychology, University of Gothenburg. Y.Q. was
supported by grants from the Beijing Natural Science Foundation (5184035) and CAS
Key Laboratory of Behavioral Science, Institute of Psychology. N.A.C. was supported
by the National Science Foundation Graduate Research Fellowship (R010138018). We
acknowledge the following research assistants: J. Muriithi and J. Ngugi (United States
International University Africa); E. Adamo, D. Cafaro, V. Ciambrone, F. Dolce and E.
Tolomeo (Magna Græcia University of Catanzaro); E. De Stefano (University of Padova);
S. A. Escobar Abadia (University of Lincoln); L. E. Grimstad (Norwegian School of
Economics (NHH)); L. C. Zamora (Franklin and Marshall College); R. E. Liang and R.
C. Lo (Universiti Tunku Abdul Rahman); A. Short and L. Allen (Massey University, New
Zealand), A. Ateş, E. Güneş and S. Can Özdemir (Boğaziçi University); I. Pedersen and T.
Roos (Åbo Akademi University); N. Paetz (Escuela de Comunicación Mónica Herrera);
J. Green (University of Gothenburg); M. Krainz (University of Vienna, Austria); and B.
Todorova (University of Vienna, Austria). The funders had no role in study design, data
collection and analysis, decision to publish or preparation of the manuscript.https://www.nature.com/nathumbehav/am2023BiochemistryGeneticsMicrobiology and Plant Patholog
The effects of diets enriched in omega-3 polyunsaturated fatty acids on systemic vaccinia virus infection
Omega-3 polyunsaturated fatty acids (PUFA, n-3 fatty acids), the key components of fish and flaxseed oils, are increasingly consumed by the public because of their potential health benefits and are available by prescription for hypertriglyceridemia. However, numerous studies have shown that these compounds are immunoregulatory and immunosuppressive and thus may increase susceptibility to infection. In this study, we tested the effects of the amount of fat and the types of fatty acid in the diet on infection by vaccinia virus, an acute infection that begins in the respiratory tract and spreads by viremia to internal organs. Male C57Bl6 mice (~5 week old) were fed for 3 weeks prior to infection and continuing during infection and recovery one of the following: 1) a normal low fat (13% kcal) diet, 2) a low fat diet containing n-3 PUFAs, 3) a high fat (41% kcal) diet rich in n-3 PUFAs, 4) a high fat n-6 PUFA diet, or 5) a high fat monounsaturated diet. We found no statistically significant differences in the susceptibility of mice to viral infection, morbidity, viral organ titers, recovery time, or mortality with these diets, indicating that, over this approximately 6-week time period, dietary fats did not substantially affect responses to poxviral infection
Development of improved therapeutic mesothelin-based vaccines for pancreatic cancer
Pancreatic cancer is the 5th leading cause of cancer deaths, and there are no effective treatments. We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine. Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment. We show here that the modified vaccinia virus Ankara (MVA) virus expressing mesothelin and the enhanced MVA virus missing the immunosuppressive A35 gene and expressing mesothelin were both safe in mice and were able to induce IFN-gamma secreting T cells in response to mesothelin expressing tumor cells. In addition, the MVA virus has oncolytic properties in vitro as it can replicate in and kill Panc02 pancreatic adenocarcinoma cell line tumor cells, even though it is unable to replicate in most mammalian cells. Deletion of the A35 gene in MVA improved T cell responses as expected. However, we were unable to demonstrate inhibition of Panc02 tumor growth in immunocompetent mice with pre-vaccination of mice, boosts, or even intratumoral injections of the recombinant viruses. Vaccine efficacy may be limited by shedding of mesothelin from tumor cells thus creating a protective screen from the immune system
Treatment of tumor bearing mice.
<p>C57BL/6 mice were injected s.c. in one flank with 640,000 wild type Panc02 cells. At 11, 18, and 25 days (arrows) post tumor injection, mice were injected i.m. contralaterally with PBS or 7.6 x 10<sup>7</sup> pfu/mouse of MVA, MVAmeso (Meso) or MVAmesoA35Del (A35D) viruses in 25 ul. (A) Tumor volumes were measured 3 times per week and survival (B) was monitored.</p
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