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Germline Transgenesis And Insertional Mutagenesis In Schistosoma Mansoni Mediated By Murine Leukemia Virus, Gabriel Rinaldi, Sabine E. Eckert, Isheng J. Tsai, Suttas Suttiprapa, Kristine J. Kines, Jose F. Tort, Victoria H. Mann, Daniel J. Turner, Matthew Berriman, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Functional studies will facilitate characterization of role and essentiality of newly available genome sequences of the human schistosomes, Schistosoma mansoni, S. japonicum and S. haematobium. To develop transgenesis as a functional approach for these pathogens, we previously demonstrated that pseudotyped murine leukemia virus (MLV) can transduce schistosomes leading to chromosomal integration of reporter transgenes and short hairpin RNA cassettes. Here we investigated vertical transmission of transgenes through the developmental cycle of S. mansoni after introducing transgenes into eggs. Although MLV infection of schistosome eggs from mouse livers was efficient in terms of snail infectivity, >10-fold higher transgene copy …

Is Human Immunodeficiency Virus Infection A Risk Factor For Strongyloides Stercoralis Hyperinfection And Dissemination, Marc O. Siegel, Gary L. Simon

Medicine Faculty Publications

No abstract provided.

Il-4 Engagement Of The Type 1 Il-4 Receptor Complex Enhances Mouse Eosinophil Migration To Eotaxin-1 In Vitro, Nicola M. Heller, William M. Gwinn, Raymond P. Donnelly, Stephanie L. Constant, Achsah D. Keegan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Previous work from our laboratory demonstrated that IL-4Rα expression on a myeloid cell type was responsible for enhancement of Th2-driven eosinophilic inflammation in a mouse model of allergic lung inflammation. Subsequently, we have shown that IL-4 signaling through type I IL-4 receptors on monocytes/macrophages strongly induced activation of the IRS-2 pathway and a subset of genes characteristic of alternatively activated macrophages. The direct effect(s) of IL-4 and IL-13 on mouse eosinophils are not clear. The goal of this study was determine the effect of IL-4 and IL-13 on mouse eosinophil function.

Methods

Standard Transwell chemotaxis assay was used to …

Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract., Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Sheng, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Epidemiology Faculty Publications

Background

We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.

Methods

CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200–500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.

Results

CVL exhibited broad anti-HIV activity against multiple laboratory-adapted and transmitted/founder (T/F) viruses, with anti-HIV activity ranging from 0 to 100% …

Vasa-Like Dead-Box Rna Helicases Of Schistosoma Mansoni, Danielle E. Skinner, Gabriel Rinaldi, Sutas Suttiprapa, Victoria H. Mann, Pablo Smircich, Alexis A. Cogswell, David L. Williams, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Genome sequences are available for the human blood flukes, Schistosoma japonicum, S. mansoni and S. haematobium. Functional genomic approaches could aid in identifying the role and importance of these newly described schistosome genes. Transgenesis is established for functional genomics in model species, which can lead to gain- or loss-of-functions, facilitate vector-based RNA interference, and represents an effective forward genetics tool for insertional mutagenesis screens. Progress toward routine transgenesis in schistosomes might be expedited if germ cells could be reliably localized in cultured schistosomes. Vasa, a member of the ATP-dependent DEAD-box RNA helicase family, is a prototypic marker of …

An Early Assessment Of The Potential Impact Of Texas' "Affiliation" Regulation On Access To Care For Low-Income Women, Peter Shin, Jessica Sharac, Sara J. Rosenbaum

Geiger Gibson/RCHN Community Health Foundation Research Collaborative

This analysis provides an initial assessment of the implications for low-income women of Texas' "affiliation regulation," which would bar Planned Parenthood Federation of America (PPFA) clinics from participating in the Texas Women's Health Program (WHP). In 2010, more than 183,000 women were enrolled in the WHP, which provides health screening, family planning and birth control to low-income women, and nearly 106,000 received care through the program. In our analysis of WHP provider data, we find:

• Planned Parenthood (PPFA) clinics are by far the dominant source of care under the WHP. In FY 2010, PPFA clinics accounted for approximately 49 percent …

Revised: An Early Assessment Of The Potential Impact Of Texas’ “Affiliation” Regulation On Access To Care For Low-Income Women, Peter Shin, Jessica Sharac, Sara J. Rosenbaum

Geiger Gibson/RCHN Community Health Foundation Research Collaborative

No abstract provided.

Time-Series Model To Predict Impact Of H1n1 Influenza On A Children's Hospital., Michael C. Spaeder, Jonathan R. Stroud, Xiaoyan Song

Pediatrics Faculty Publications

The spring of 2009 witnessed the emergence of a novel influenza A(H1N1) virus resulting in the first influenza pandemic since 1968. In autumn of 2010, the 2009 novel H1N1 influenza strain re-emerged. We performed a retrospective time-series analysis of all patients with laboratory-confirmed H1N1 influenza who presented to our institution during 2009. Cases of influenza were assembled into 3-day aggregates and forecasting models of H1N1 influenza incidence were created. Forecasting estimates of H1N1 incidence for the 2010–2011 season were compared to actual values for our institution to assess model performance. Ninety-five percent confidence intervals calculated around our model's forecasts were …

Elevated Plasma Il-6 Associates With Increased Risk Of Advanced Fibrosis And Cholangiocarcinoma In Individuals Infected By Opisthorchis Viverrini, Banchob Sripa, Bandit Thinkhamrop, Eimorn Mairiang, Thewarach Laha, Sasithorn Kaewkes, Paiboon Sithithaworn, Maria V. Periago, Vajarabhongsa Bhudhisawasdi, Ponlapat Yonglitthipagon, Jason Mulvenna, Paul J. Brindley, Alex Loukas, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and …

Prioritization Of Biomarker Targets In Human Umbilical Cord Blood: Identification Of Proteins In Infant Blood Serving As Validated Biomarkers In Adults, Nicole Hansmeier, Tzu-Chiao Chao, Lynn R. Goldman, Frank R. Witter, Rolf U. Halden

Environmental and Occupational Health Faculty Publications

Background: Early diagnosis represents one of the best lines of defense in the fight against a wide array of human diseases. Umbilical cord blood (UCB) is one of the first easily available diagnostic biofluids and can inform about the health status of newborns. However, compared with adult blood, its diagnostic potential remains largely untapped.

Objectives: Our goal was to accelerate biomarker research on UCB by exploring its detectable protein content and providing a priority list of potential biomarkers based on known proteins involved in disease pathways.

Methods: We explored cord blood serum proteins by profiling a UCB pool of 12 …

Development Stage-Specific Proteomic Profiling Uncovers Small, Lineage Specific Proteins Most Abundant In The Aspergillus Fumigatus Conidial Proteome, Moo-Jin Suh, Natalie D. Fedorova, Steven E. Cagas, Susan Hastings, Robert D. Fleischmann, Scott N. Peterson, David S. Perlin, William C. Nierman, Rembert Pieper, Michelle Momany

Biochemistry and Molecular Medicine Faculty Publications

Background

The pathogenic mold Aspergillus fumigatus is the most frequent infectious cause of death in severely immunocompromised individuals such as leukemia and bone marrow transplant patients. Germination of inhaled conidia (asexual spores) in the host is critical for the initiation of infection, but little is known about the underlying mechanisms of this process.

Results

To gain insights into early germination events and facilitate the identification of potential stage-specific biomarkers and vaccine candidates, we have used quantitative shotgun proteomics to elucidate patterns of protein abundance changes during early fungal development. Four different stages were examined: dormant conidia, isotropically expanding conidia, hyphae …

Demographics And Survival Of Aids Cases With Cancer, Washington, Dc, 1996-2006, Heather A. Young, Eric Engels, Anne-Marie Sufian-Kargbo, Alicia Vargas, Kathleen Rogers, Tiffany West, Amanda D. Castel

Epidemiology Faculty Publications

Background

Washington, DC (DC) has one of the highest HIV/AIDS rates in the U.S and cancer is the second leading cause of death among DC residents. This study sought to examine the demographic characteristics and survival of persons with AIDS defining cancers (ADCs) compared to those with non-AIDS defining cancers (NADCs) between the early HAART era (1996-2001) and the late HAART era (2002-2006) in DC.

Methods

Cases reported from 1996-2006 to the DC Cancer Registry and the AIDS Surveillance Registry were linked using a probabilistic matching algorithm. Cases were included if the cancer occurred from 4 months to 60 months …

Modulation Of Gsk-3Β Activity In Venezuelan Equine Encephalitis Virus Infection, Kylene Kehn-Hall, Aarthi Narayanan, Lindsay Lundberg, Gavin Sampey, Chelsea Pinkham, Irene Guendel, Rachel Van Duyne, Svetlana Senina, Kimberly L. Schultz, Eric Stavale, M. Javad Aman, Charles Bailey, Fatah Kashanchi

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Alphaviruses, including Venezuelan Equine Encephalitis Virus (VEEV), cause disease in both equine and humans that exhibit overt encephalitis in a significant percentage of cases. Features of the host immune response and tissue-specific responses may contribute to fatal outcomes as well as the development of encephalitis. It has previously been shown that VEEV infection of mice induces transcription of pro-inflammatory cytokines genes (e.g., IFN-γ, IL-6, IL-12, iNOS and TNF-α) within 6 h. GSK-3β is a host protein that is known to modulate pro-inflammatory gene expression and has been a therapeutic target in neurodegenerative disorders such as Alzheimer's. Hence inhibition of GSK-3β …

Medicine + Health, Spring 2012, George Washington University, School Of Medicine And Health Sciences, Office Of Communications And Marketing

Medicine + Health Magazine

No abstract provided.

Genetic Manipulation Of Schistosomes - Progress With Integration Competent Vectors, Sutas Suttiprapa, Gabriel Rinaldi, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Draft genome sequences for Schistosoma japonicum and S. mansoni are now available. The schistosome genome encodes ∼13 000 protein-encoding genes for which the functions of few are well understood. Nonetheless, the new genes represent potential intervention targets, and molecular tools are being developed to determine their importance. Over the past 15 years, noteworthy progress has been achieved towards development of tools for gene manipulation and transgenesis of schistosomes. A brief history of genetic manipulation is presented, along with a review of the field with emphasis on reports of integration of transgenes into schistosome chromosomes.

Five-Year Longitudinal Assessment Of The Downstream Impact On Schistosomiasis Transmission Following Closure Of The Three Gorges Dam., Darren J. Gray, Aaron P. Thrift, Gail M. Williams, Feng Zheng, Yue-Sheng Li, Jiagang Guo, Honggen Chen, Tianping Wang, Xin J. Xu, Rong Zhu, Hongqing Zhu, Chun Li Cao, Dan D. Lin, Zhen Y. Zhao, Robert S. Li, George M. Davis, Donald P. Mcmanus

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Schistosoma japonicum is a major public health concern in the Peoples' Republic of China (PRC), with about 800,000 people infected and another 50 million living in areas at risk of infection. Based on ecological, environmental, population genetic and molecular factors, schistosomiasis transmission in PRC can be categorised into four discrete ecosystems or transmission modes. It is predicted that, long-term, the Three Gorges Dam (TGD) will impact upon the transmission of schistosomiasis in the PRC, with varying degree across the four transmission modes.

Methodology/Principal Findings

We undertook longitudinal surveillance from 2002 to 2006 in sentinel villages of the three transmission …

Health Information Privacy In The Correctional Environment, Melissa M. Goldstein

Health Policy and Management Faculty Publications

Information technology is considered a transformative element in health care because it facilitates the transparency and sharing of health information, which have always been central to the practice of medicine and the delivery of high-quality care. The widespread use of electronic health records (EHRs) and electronic health information exchange, among other technologies, is considered essential to improving the quality of care, reducing medical errors, reducing health disparities, and advancing the delivery of patient-centered medical care.

Enhanced Protective Efficacy Of A Chimeric Form Of The Schistosomiasis Vaccine Antigen Sm-Tsp-2, Mark S. Pearson, Darren A. Pickering, Henry J. Mcsorley, Jeffrey M. Bethony, Leon Tribolet, Annette M. Dougall, Peter J. Hotez, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG1 and IgG3 from putatively resistant individuals resident in S. mansoniendemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to …

Characterising The Mucosal And Systemic Immune Responses To Experimental Human Hookworm Infection., Soraya Gaze, Henry J. Mcsorley, James Daveson, Di Jones, Jeffrey M. Bethony, Luciana M. Oliveira, Richard Speare, James S. Mccarthy, Christian R. Engwerda, John Croese, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after …

Environmental Drivers Of Ross River Virus In South-East Tasmania, Australia: Towards Strengthening Public Health Interventions, Angela Werner, Sarah Goater, Scott Carver, Greg Robertson, Philip Weinstein

Global Health Faculty Publications

In Australia, Ross River virus (RRV) is predominantly identified and managed through passive health surveillance. Here, the proactive use of environmental datasets to improve community-scale public health interventions in southeastern Tasmania is explored. Known environmental drivers (temperature, rainfall, tide) of the RRV vector Aedes camptorhynchus are analysed against cumulative case records for five adjacent local government areas (LGAs) from 1993 to 2009. Allowing for a 0- to 3-month lag period, temperature was the most significant driver of RRV cases at 1-month lag, contributing to a 23. 2% increase in cases above the long-term case average. The potential for RRV to …

Utility Of Serum Procalcitonin Values In Patients With Acute Exacerbations Of Chronic Obstructive Pulmonary Disease: A Cautionary Note, Ann R. Falsey, Kenneth L. Becker, Andrew J. Swinburne, Eric S. Nylen, Richard H. Snider, Maria A. Formica, Patricia A. Hennessey, Mary M. Criddle, Derick R. Peterson, Edward E. Walsh

Medicine Faculty Publications

Background: Serum procalcitonin levels have been used as a biomarker of invasive bacterial infection and recently have been advocated to guide antibiotic therapy in patients with chronic obstructive pulmonary disease (COPD). However, rigorous studies correlating procalcitonin levels with microbiologic data are lacking. Acute exacerbations of COPD (AECOPD) have been linked to viral and bacterial infection as well as noninfectious causes. Therefore, we evaluated procalcitonin as a predictor of viral versus bacterial infection in patients hospitalized with AECOPD with and without evidence of pneumonia.

Methods: Adults hospitalized during the winter with symptoms consistent with AECOPD underwent extensive testing for viral, bacterial, …

Localization And Sub-Cellular Shuttling Of Htlv-1 Tax With The Mirna Machinery, Rachel Van Duyne, Irene Guendel, Zachary Klase, Aarthi Narayanan, William Coley, Elizabeth Jaworski, Jessica Roman, Anastas Popratiloff, Renaud Mahieux, Kylene Kehn-Hall, Fatah Kashanchi

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in …

Redefining Chronic Toxoplasmosis: A T Cell Exhaustion Perspective, Rajarshi Bhadra, Imtiaz A. Khan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

The Adjuvanticity Of An O. Volvulus-Derived Rov-Asp-1 Protein In Mice Using Sequential Vaccinations And In Non-Human Primates, Jing Wang, Nancy Trichoche, Lanying Du, Meredith Hunter, Bin Zhan, Gaddam Goud, Elizabeth S. Didier, Jing Liu, Lu Lu, Preston A. Marx, Shibo Jiang, Sara Lustigman

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulusrecombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the r …

Application Of Nanomedicine In Emergency Medicine: Point-Of-Care Testing And Drug Delivery In Twenty - First Century, Ali Pourmand, Mohammed Reza Pourmand, Justin Wang, Robert Shesser

Emergency Medicine Faculty Publications

The application of emerging nanotechnology to the practice of medicine represents a frontier of nanomedicine. Nanomedicine has been defined as a science which emphasizes the use of nanoscale tools in conjunction with background knowledge of the human body for medical diagnosis and treatment. Application of nanomedicine in EM may give EM providers the opportunity to diagnose and treat life-threatening diseases in a shorter period of time. These applications include diagnostic utilities, preventive medicine, targeted pharmacotherapy, and tissue regeneration.

Impact Of Antiviral Treatment And Hospital Admission Delay On Risk Of Death Associated With 2009 A/H1n1 Pandemic Influenza In Mexico, Gerardo Chowell, Cecile Viboud, Lone Simonsen, Mark A. Miller, Santiago Echevarría-Zuno, Margotx González-León, Víctor H. Borja Aburto

Global Health Faculty Publications

Background

Increasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe outcomes of 2009 A/H1N1 influenza infections in different populations (e.g., [1-5]), analyses of the determinants of mortality risk spanning multiple pandemic waves and geographic regions are scarce. Between-country differences in the mortality burden of the 2009 pandemic could be linked to differences in influenza case management, underlying population health, …

Hiv-1 Resistant Cdk2-Knockdown Macrophage-Like Cells Generated From 293t Cell-Derived Human Induced Pluripotent Stem Cells, Marina Jerebtsova, Namita Kumari, Min Xu, Gustavo Brito Alvim De Melo, Xiaomei Niu, Kuan-Teh Jeang, Sergei Nekhai

Pediatrics Faculty Publications

A major challenge in studies of human diseases involving macrophages is low yield and heterogeneity of the primary cells and limited ability of these cells for transfections and genetic manipulations. To address this issue, we developed a simple and efficient three steps method for somatic 293T cells reprogramming into monocytes and macrophage-like cells. First, 293T cells were reprogrammed into induced pluripotent stem cells (iPSCs) through a transfection-mediated expression of two factors, Oct-4 and Sox2, resulting in a high yield of iPSC. Second, the obtained iPSC were differentiated into monocytes using IL-3 and M-CSF treatment. And third, monocytes were differentiated into …

Reasons For Low Pandemic H1n1 2009 Vaccine Acceptance Within A College Sample, Russell D. Ravert, Linda Y. Fu

Pediatrics Faculty Publications

This study examined health beliefs associated with novel influenza A (H1N1) immunization among US college undergraduates during the 2009-2010 pandemic. Undergraduates (ages 18–24 years) from a large Midwestern University were invited to complete an online survey during March, 2010, five months after H1N1 vaccines became available. Survey items measured H1N1 vaccine history and H1N1-related attitudes based on the health belief literature. Logistic regression was used to identify attitudes associated with having received an H1N1 vaccine, and thematic analysis of student comments was conducted to further understand influences on vaccine decisions. Among the 296 students who participated in the survey, 15.2% …

Pulmonary And Peritoneal Tuberculosis Associated With Tumor Necrosis Factor-Alpha Inhibitor Use: A Case Report And Review Of The Literature, Niharika Tipirneni, Marc O. Siegel

Medicine Faculty Publications

The association between the use of tumor necrosis factor-α inhibitors and the increased risk of granulomatous infections, especially tuberculosis, has been well documented. Given the rapidly expanding list of inflammatory conditions for which tumor necrosis factor-α inhibitors are receiving FDA approval, the incidence of tuberculosis in this patient population has increased. Despite heightened awareness by physicians, the diagnosis of tuberculosis can remain challenging, given that extrapulmonary sites of infection are more frequently involved. We present a case of pulmonary and peritoneal tuberculosis in a gentleman being treated with a tumor necrosis factor-α inhibitor and discuss the diagnostic challenges of establishing …

Etravirine Induced Severe Hypersensitivity Reaction And Fulminant Hepatitis: A Case Report And Review Of The Literature., Linda Nabha, Gayle P. Balba, Princy N.S. Kumar, Carmelita Tuazon

Medicine Faculty Publications

We report the first published case of etravirine induced hypersensitivity reaction leading to fulminant hepatic failure in a 49-year-old female patient with Human Immunodefi ciency Virus. She presented with a life threatening rash and end stage organ damage requiring intensive care unit supportive care. Liver biopsy supported the diagnosis of drug-induced hypersensitivity. The patient recovered after withdrawal of etravirine and the use of systemic corticosteroids. The authors describe etravirine drug hypersensitivity as a clinically important reaction and that early recognition can improve survival.