Modulating Influenza and Heparin Binding Viruses’ Pathogenesis with Extrinsic Receptor Decoy Liposomes: A Dissertation
Influenza is a severe disease in humans and animals, causing upwards of 40,000 deaths every year in America alone. Influenza A virus (IAV) also causes periodic pandemics every 10 to 50 years, killing millions of people. Despite this, very few effective therapies are available. All strains of IAV are prone to developing resistance to antibodies due to the high mutation rate in the viral genome. Because of this mutation rate, a yearly vaccine must be generated before every flu season, and efficacy varies year to year. IAV has also mutated to escape several of the clinically-approved small molecule inhibitors. A therapeutic agent that targets a highly conserved region of the virus could bypass resistance and also be effective against multiple strains of IAV. IAV attachment is mediated by many individually weak hemagglutinin–sialic acid interactions that all together make a strong attachment to a host cell. Polymerized sialic acid analogs can recreate these interactions and block infection. However, they are not ideal therapeutics due to solubility issues and in vivo toxicity. We used liposomes as a novel means for delivery of the sialic acid-containing glycan, sialylneolacto-N-tetraose c (LSTc). LSTcbearing decoy liposomes form multivalent, polymer-like interactions with IAV. Decoy liposomes competitively bind IAV in hemagglutination inhibition assays and inhibit infection of target cells in a dose-dependent manner. LSTc decoy liposomes co-localize with IAV, while control liposomes do not. Inhibition is specific, as inhibition of Sendai virus and respiratory syncytial virus is not observed. In contrast, monovalent LSTc does not bind IAV or inhibit infectivity. LSTc decoy liposomes prevent the spread of IAV during multiple rounds of replication in vitro and extend survival of mice challenged with a lethal dose of virus. Considering the conservation of the hemagglutinin binding pocket and the ability of decoy liposomes to form high-avidity interactions with IAV hemagglutinin, our decoy liposomes have potential as a new therapeutic agent against emerging strains.
The dynamics of T cell responses have been extensively studied during single virus infection of naïve mice. During a viral infection, viral antigen is presented in the context of MHC class I molecules on the surface of infected cells. Activated CD8 T cells that recognized viral antigens mediate clearance of virus through lysis of these infected cells. We hypothesize that the balance between the replicating speed of the virus and the efficiency at which the T cell response clears the virus is key in determining the disease outcome of the host. Lower T cell efficiency and delayed viral clearance can lead to extensive T cellmediated immunopathology and death in some circumstances. To examine how the efficiency of the immune response would impact immunopathology we studied several viral infection models where T cell responses were predicted to be less than optimal: 1. a model of co-infection with two viruses that contain a crossreactive epitope, 2. a viral infection model where a high dose infection is known to induce clonal exhaustion of the CD8 T cell response, 3. a neonatal virus infection model where the immune system is immature and 4. A model of beneficial heterologous immunity and T cell crossreactivity where mice are immunized as neonates when the T cell pool is still developing.
Model 1. Simultaneous co-infections are common and can occur from mosquito bites, contaminated needle sticks, combination vaccines and the simultaneous administration of multiple vaccines. Using two distantly related arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PICV), we questioned if immunological T cell memory and subsequent protection would be altered following a simultaneous co-infection, where two immune responses are generated within the same host at the same time. Coinfection with these two viruses, which require CD8 T cell responses to clear, resulted in decreased immune protection and enhanced immunopathology after challenge with either virus. After primary co-infection, each virus-specific immune response impacted the other as they competed within the same host and resulted in several significant differences in the CD8 T cell responses compared to mice infected with a single virus. Co-infected mice had a dramatic decrease in the overall size of the LCMV-specific CD8 T cell response and variability in which virus-specific response dominated, along with skewing in the immunodominance hierarchies from the normal responses found in single virus infected mice. The reduction in the number of LCMV-specific CD8 memory T cells, specifically cells with an effector memory-like phenotype, was associated with higher viral loads and increased liver pathology in co-infected mice upon LCMV challenge. The variability in the immunodominance hierarchies of co-infected mice resulted in an enhanced cross-reactive response in some mice that mediated enhanced immune-mediated fat pad pathology during PICV challenge. In both viral challenge models, an ineffective memory T cell response in co-infected mice facilitated increased viral replication, possibly leading to enhanced and prolonged accumulation of secondary effector T cells in the tissues, thereby leading to increased immune pathology. Thus, the magnitude and character of memory CD8 T cell responses in simultaneous co-infections differed substantially from those induced by single immunization. This has implications for the design of combination vaccines and scheduling of simultaneous immunizations.
Model 2. The balance between protective immunity and immunopathology often determines the fate of the virus-infected host. Several human viruses have been shown to induce a wide range of severity of disease. Patients with hepatitis B virus (HBV), for example, show disease progression ranging from acute resolving infection to a persistent infection and fulminant hepatitis. Certain rapidly replicating viruses have the ability to clonally exhaust the T cell response, such as HBV and hepatitis C virus (HCV) in humans and the clone 13 strain of LCMV in mice. How rapidly virus is cleared is a function of initial viral load, viral replication rate, and efficiency of antigen-specific T cells. By infecting mice with three different inocula of LCMV clone 13, we questioned how the race between virus replication and T cell responses could result in different disease outcomes. A low dose of LCMV generated efficient CD8 T effector cells, which cleared the virus with minimal lung and liver pathology. A high dose of LCMV resulted in clonal exhaustion of T cell responses, viral persistence and little immunopathology. An intermediate dose only partially exhausted the CD8 T cell responses and was associated with significant mortality, and the surviving mice developed viral persistence and massive immunopathology, including necrosis of the lungs and liver. This was a T cell-mediated disease as T cell-deficient mice had no pathology and became persistently infected like mice infected with a high dose of LCMV clone 13. This suggests that for non-cytopathic viruses like LCMV, HCV and HBV, clonal exhaustion may be a protective mechanism preventing severe immunopathology and death.
Model 3. Newborns are more susceptible to infections due to their lack of immunological memory and under-developed immune systems. Passive maternal immunity helps protect neonates until their immune systems have matured. We questioned if a noncytolytic virus that produces strong T cell responses in adult mice would also induce an equally effective response in neonatal mice. Neonates were infected with very low doses of LCMV Armstrong and surprisingly the majority succumbed to infection between days 7-11, which is the peak of the T cell response in adult mice infected with LCMV. Death was caused by T cell-dependent pathology and not viral load as 100% of T cell deficient neonates survived with minimal lung and liver pathology. This is similar to the adult model of medium dose LCMV clone 13, but T cell responses in neonates were not partially clonal exhausted. Furthermore, surviving neonates were not persistently infected, clearing virus by day 14 post infection. In adult mice direct intracranial infection leads to LCMV replication and CD8 T cell infiltration in the central nervous system (CNS), causing CD8 T cell-mediated death. However, this does not occur in adults during LCMV intraperitoneal (ip) infections. We questioned if unlike adults LCMV could be gaining access to the CNS in neonates following ip infection. Replicating LCMV was found in the brain of neonates after day 5 post infection along with virus-specific CD8 T cells producing IFNγ at day 9 post infection. Neonates lacking perforin had complete survival when followed until day 14 post infection, suggesting perforin-mediated T cell-dependent immunopathology within the CNS of neonates was causing death after LCMV infection. Passive immunity from LCMV-immune mothers also protected 100% of pups from death by helping control viral load early in infection. We believe that the maternal antibody compensates for the immature innate immune response of neonates and controls viral replication early so the neonatal T cell response induced less immunopathology. Neonates are commonly thought to have less functional immune systems, but these results show that neonates are capable of producing strong T cell responses that contribute to increased mortality.
Model 4. Due to their enhanced susceptibility to infection neonatal and infant humans receive multiple vaccines. Several non-specific effects from immunizations have been observed, for example, measles or Bacillus Calmette- Guerin (BCG) vaccines have been linked to decreased death of children from infections other than measles virus or tuberculosis. These studies mirror the concepts of beneficial heterologous immunity, where previous immunization with an unrelated pathogen can result in faster viral clearance. LCMV-immune mice challenged with vaccinia virus (VV) have lower viral loads then naïve mice and survive lethal infections, but some mice do develop fat pad immunopathology in the form of panniculitis or acute fatty necrosis (AFN). We questioned how immunological T cell memory formed during the immature neonatal period would compare to memory generated in fully mature adults during a heterologous viral challenge. Mice immunized as neonates had comparable reduction in VV load and induction of AFN, indicating that heterologous immunity is established during viral infections early in life. Interestingly, the LCMV-specific memory populations that expanded in mice immunized as neonates differed from that of mice immunized as adults. In adult mice 50% of the mice have an expansion of LCMVNP205- specific CD8 T cells while the majority of neonates expanded the LCMVGP34- specific CD8 T cell pool. This alteration in dominant crossreactivities may be due to the limited T cell receptor repertoire of neonatal mice. In naïve neonatal mice we found altered Vβ repertoires within the whole CD8 T cell pool. Furthermore, there was altered Vβ usage within virus-specific responses compared to adult mice and a wide degree of variability between individual neonates, suggesting enhanced private specificity of the TCR repertoire. Beneficial heterologous immunity is maintained in neonates, but there was altered usage of crossreactive responses.
As neonatal mice were found to be so sensitive to LCMV infection we questioned if neonates could control another arena virus that did not replicate as efficiently in mice, PICV. Unlike LCMV infection, neonatal mice survived infection with PICV even with adult-like doses. However, viral clearance was protracted in neonates compared to adults, but was cleared from fat pad and kidney by day 11 post infection. The peak of the CD8 T cell response was similarly delayed. PICV infected neonates showed dose-dependent PICV-specific CD8 T cell responses,
which were similar to adult responses by frequency, but not total number. As with LCMV infection there were changes in immunodominance hierarchies in neonates. Examination of the immunodominance hierarchies of PICV-infected neonates showed that there were adult-like responses to the dominant NP38- specific response, but a loss of the NP122-specific response. Six weeks post neonatal infection mice were challenged with LCMV Armstrong and there was a strong skewing of the PICV immunodominance hierarchy to the crossreactive NP205-specific response. These data further support the hypothesis that heterologous immunity and crossreactivity develop following neonatal immunization, much as occurs in adults, although TCR repertoire and crossreactive patterns may differ.
Changing the balance between T cell efficiency and viral load was found to altered the severity of the developing immunopathology after viral infection.
Uncovering the evidence: Systematic review of interventions to reduce oral health disparities between adults with Intellectual Disability and the general population
Oral health is a public health concern for people with intellectual or developmental disabilities (I/DD). Research consistently shows that the population with I/DD experiences poorer oral hygiene, higher prevalence and severity of periodontal disease, and higher incidence of untreated caries when compared to the general population. Poor oral health can cause chronic pain, affect the ability to eat and communicate, and adversely affect physical health and quality of life. Intervention strategies include enhanced prevention, increased routine care, expanded insurance coverage, and training for dentists and hygienists. Research is needed to identify the most effective interventions. A standard systematic literature review for evidence-based practices is not adequate for identifying and evaluating the evidence in areas such as health policy and individual health behaviors. This presentation describes the structured processes used in uncovering evidence where there is limited published literature that includes 1) the I/DD population and 2) traditional scientific reviews of interventions addressing their oral health. By adapting a transdisciplinary conceptual model, which could be applied to a multitude of disciplines, we identify the best available evidence as collected through a conventional systematic review, allowing for additional emphasis on the personal, social and environmental factors that affect the I/DD population. The process includes search strategies to include peer reviewed and gray literature, along with other associated programs, policies, and practices, resulting in a unique evidence base from varied sources. Additionally, we frame and refine a formal plan to review the outcomes and establish a level of evidence for the identified interventions.
Chronic kidney disease and outcomes in heart failure with preserved versus reduced ejection fraction: the Cardiovascular Research Network PRESERVE Study
BACKGROUND: There is scant evidence on the effect that chronic kidney disease (CKD) confers on clinically meaningful outcomes among patients with heart failure with preserved left ventricular ejection fraction (HF-PEF).
METHODS AND RESULTS: We identified a community-based cohort of patients with HF. Electronic medical record data were used to divide into HF-PEF and reduced left ventricular EF on the basis of quantitative and qualitative estimates. Level of CKD was assessed by estimated glomerular filtration rate (eGFR) and by dipstick proteinuria. We followed patients for a median of 22.1 months for outcomes of death and hospitalization (HF-specific and all-cause). Multivariable Cox regression estimated the adjusted relative-risk of outcomes by level of CKD, separately for HF-PEF and HF with reduced left ventricular EF. We identified 14 579 patients with HF-PEF and 9762 with HF with reduced left ventricular EF. When compared with patients with eGFR between 60 and 89 mL/min per 1.73 m(2), lower eGFR was associated with an independent graded increased risk of death and hospitalization. For example, among patients with HF-PEF, the risk of death was nearly double for eGFR 15 to 29 mL/min per 1.73 m(2) and 7x higher for eGFR/min per 1.73 m(2), with similar findings in those with HF with reduced left ventricular EF.
CONCLUSIONS: CKD is common and an important independent predictor of death and hospitalization in adults with HF across the spectrum of left ventricular systolic function. Our study highlights the need to develop new and effective interventions for the growing number of patients with HF complicated by CKD.
BACKGROUND: Cognitive impairment, highly prevalent in patients with heart failure (HF), increases risk for hospitalization and mortality. However, the course of cognitive change in HF is not well characterized. The purpose of this systematic review was to examine the available evidence longitudinal changes in cognitive function in patients with HF.
METHODS AND RESULTS: A literature search of several electronic databases was performed. Studies published from January 1, 1980, to September 30, 2012, that used validated measures to diagnose HF and assess cognitive function >/=2x in adults with HF were eligible for inclusion. Change in cognitive function was examined in the context of HF treatments applied (eg, medication initiation, left ventricular assist device implantation), length of follow-up, and comparison group. Fifteen studies met eligibility criteria. Significant decline in cognitive function was noted among patients with HF followed up for >1 year. Improvements in cognition were observed among patients with HF undergoing interventions to improve cardiac function (eg, heart transplantation) and among patients examined over short time periods (<1 >year). Studies comparing patients' cognition over time with their own baseline tended to report improvements, whereas studies using a comparison group without HF tended to report declines or stability in cognition over time among patients with HF.
CONCLUSIONS: Patients with HF are at increased risk for cognitive decline, but this risk seems to be modifiable with cardiac treatment. Further research is needed to identify the mechanisms that cause cognitive changes in HF.
IDEAS for a healthy baby--reducing disparities in use of publicly reported quality data: study protocol for a randomized controlled trial
BACKGROUND: Publicly reported performance on quality measures is intended to enable patients to make more informed choices. Despite the growing availability of these reports, patients' use remains limited and disparities exist. Low health literacy and numeracy are two barriers that may contribute to these disparities. Patient navigators have helped patients overcome barriers such as these in other areas, such as cancer care and may prove useful for overcoming barriers to using publicly reported quality data.
METHODS/DESIGN: The goals of this study are: to determine the efficacy of a patient navigator intervention to assist low-income pregnant women in the use of publicly available information about quality of care when choosing a pediatrician; to evaluate the relative importance of factors influencing women's choice of pediatric practices; to evaluate the effect of the intervention on patient engagement in management of their own and their child's health care; and to assess variation in efficacy of the intervention for sub-groups based on parity, age, and race/ethnicity. English speaking women ages 16 to 50 attending a prenatal clinic at a large urban medical center will be randomized to receive an in-person navigator intervention or an informational pamphlet control between 20 to 34 weeks of gestation. The intervention will include in-person guided use of the Massachusetts Health Quality Partners website, which reports pediatric practices' performance on quality measures and patient experience. The primary study outcomes will be the mean scores on a) clinical quality and b) patient experience measures.
DISCUSSION: Successful completion of the study aims will yield important new knowledge about the value of guided website navigation as a strategy to increase the impact of publicly reported quality data and to reduce disparities in use of these data.
TRIAL REGISTRATION: ClinicalTrials.gov #NCT01784575.
PURPOSE: To conduct a synthesis of the literature on methods to evaluate the impacts of FDA regulatory actions and identify best practices for future evaluations.
METHODS: We searched MEDLINE for manuscripts published between January 1948 and August 2011 that included terms related to FDA, regulatory actions, and empirical evaluation; the review additionally included FDA-identified literature. We used a modified Delphi method to identify preferred methodologies. We included studies with explicit methods to address threats to validity and identified designs and analytic methods with strong internal validity that have been applied to other policy evaluations.
RESULTS: We included 18 studies out of 243 abstracts and papers screened. Overall, analytic rigor in prior evaluations of FDA regulatory actions varied considerably; less than a quarter of studies (22%) included control groups. Only 56% assessed changes in the use of substitute products/services, and 11% examined patient health outcomes. Among studies meeting minimal criteria of rigor, 50% found no impact or weak/modest impacts of FDA actions and 33% detected unintended consequences. Among those studies finding significant intended effects of FDA actions, all cited the importance of intensive communication efforts. There are preferred methods with strong internal validity that have yet to be applied to evaluations of FDA regulatory actions.
CONCLUSIONS: Rigorous evaluations of the impact of FDA regulatory actions have been limited and infrequent. Several methods with strong internal validity are available to improve trustworthiness of future evaluations of FDA policies.
OBJECTIVE: The disclosure of medical errors has attracted considerable research interest in recent years. However, the research to date has lacked interdisciplinary dialog, making translation of findings into medical practice challenging. This article lays out the disciplinary perspectives of the fields of medicine, ethics, law and communication on medical error disclosure and identifies gaps and tensions that occur at these interdisciplinary boundaries.
METHODS: This article summarizes the discussion of an interdisciplinary error disclosure panel at the 2012 EACH Conference in St. Andrews, Scotland, in light of the current literature across four academic disciplines.
RESULTS: Current medical, ethical, legal and communication perspectives on medical error disclosure are presented and discussed with particular emphasis on the interdisciplinary gaps and tensions.
CONCLUSION: The authors encourage interdisciplinary collaborations that strive for a functional approach to understanding and improving the disclosure of medical errors with the ultimate goal to improve quality and promote safer medical care.
PRACTICE IMPLICATIONS: Interdisciplinary collaborations are needed to reconcile the needs of the stakeholders involved in medical error disclosure. A particular challenge is the effective translation of error disclosure research into practice. Concrete research questions are provided throughout the manuscript to facilitate a resolution of the tensions that currently impede interdisciplinary progress.
Effects of transitioning from conventional methods to liquid-based methods on unsatisfactory Papanicolaou tests: results from a multicenter US study
BACKGROUND: Papanicolaou (Pap) testing has transitioned from conventional preparations (CPs) to liquid-based preparations (LBPs) because of the perceived superiority of LBPs. Many studies conclude that LBPs reduce unsatisfactory Pap tests; however, some believe that the evidence substantiating this claim is weak. The authors studied the effect of the transition from CPs to LBPs on the proportion of unsatisfactory Pap tests in 4 health care systems in the United States participating in the National Institutes of Health-funded Screening Effectiveness and Research in Community-Based Healthcare (SEARCH) project.
METHODS: The study cohort consisted of 548,174 women ages 21 to 65 years who had 1443,725 total Pap tests between 2000 and 2010. Segmented regression analysis was used to estimate the effect of adopting LBPs on the proportion of unsatisfactory Pap tests after adjusting for age.
RESULTS: Three sites that implemented SurePath LBP experienced significant reductions in unsatisfactory Pap tests (estimated effect: site 1, -2.46%; 95% confidence interval [CI], -1.47%, -3.45%; site 2, -1.78%; 95% CI, -1.54%, -2.02%; site 3, -8.25%; 95% CI, -7.33%, -9.17%). The fourth site that implemented ThinPrep LBP did not experience a reduction in unsatisfactory Pap tests. The relative risk of an unsatisfactory Pap test in women aged >/= 50 years increased after the transition to LBPs (SurePath: relative risk, 2.1; 95% CI, 1.9-2.2; ThinPrep: relative risk, 1.7; 95% CI, 1.5-2.0).
CONCLUSIONS: The observed changes in the proportion of unsatisfactory Pap tests varied across the participating sites and depended on the type of LBP technology, the age of women, and the rates before the implementation of this technology.
V(D)J joining is mediated by RAG recombinase during early B-lymphocyte development in the bone marrow (BM). Activation-induced deaminase initiates isotype switching in mature B cells of secondary lymphoid structures. Previous studies questioned the strict ontological partitioning of these processes. We show that pro-B cells undergo robust switching to a subset of immunoglobulin H (IgH) isotypes. Chromatin studies reveal that in pro-B cells, the spatial organization of the Igh locus may restrict switching to this subset of isotypes. We demonstrate that in the BM, V(D)J joining and switching are interchangeably inducible, providing an explanation for the hyper-IgE phenotype of Omenn syndrome.
Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type-specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.
Despite advances in DNA sequencing technology, assembly of complex genomes remains a major challenge, particularly for genomes sequenced using short reads, which yield highly fragmented assemblies. Here we show that genome-wide in vivo chromatin interaction frequency data, which are measurable with chromosome conformation capture-based experiments, can be used as genomic distance proxies to accurately position individual contigs without requiring any sequence overlap. We also use these data to construct approximate genome scaffolds de novo. Applying our approach to incomplete regions of the human genome, we predict the positions of 65 previously unplaced contigs, in agreement with alternative methods in 26/31 cases attempted in common. Our approach can theoretically bridge any gap size and should be applicable to any species for which global chromatin interaction data can be generated.
Biological networks can be used to functionally annotate genes on the basis of interaction-profile similarities. Metrics known as association indices can be used to quantify interaction-profile similarity. We provide an overview of commonly used association indices, including the Jaccard index and the Pearson correlation coefficient, and compare their performance in different types of analyses of biological networks. We introduce the Guide for Association Index for Networks (GAIN), a web tool for calculating and comparing interaction-profile similarities and defining modules of genes with similar profiles.
Influenza A and B viruses form different genera, which were originally distinguished by antigenic differences in their nucleoproteins and matrix 1 proteins. Cross-protection between these two genera has not been observed in animal experiments, which is consistent with the low homology in viral proteins common to both viruses except for one of three polymerase proteins, polymerase basic 1 (PB1). Recently, however, antibody and CD4+ T cell epitopes conserved between the two genera were identified in humans. A protective antibody epitope was located in the stalk region of the surface glycoprotein, hemagglutinin, and a CD4+ T cell epitope was located in the fusion peptide of the hemagglutinin. The fusion peptide was also found to contain antibody epitopes in humans and animals. A short stretch of well-conserved peptide was also identified in the other surface glycoprotein, neuraminidase, and antibodies binding to this peptide were generated by peptide immunization in rabbits. Although PB1, the only protein which has relatively high overall sequence homology between influenza A and B viruses, is not considered an immunodominant protein in the T cell responses to influenza A virus infection, amino acid sequence comparisons show that a considerable number of previously identified T cell epitopes in the PB1 of influenza A viruses are conserved in the PB1 of influenza B viruses. These data indicate that B and T cell cross-reactivity exists between influenza A and B viruses, which may have modulatory effects on the disease process and recovery. Although the antibody titers and the specific T cell frequencies induced by natural infection or standard vaccination may not be high enough to provide cross protection in humans, it might be possible to develop immunization strategies to induce these cross-reactive responses more efficiently.
Effect of Race/Ethnicity and Socioeconomic Status on Pandemic H1N1-Related Outcomes in Massachusetts
Objectives. We linked hospital discharge and American Community Survey and US Census data to investigate 2009 H1N1 influenza (H1N1)-related outcomes by racial/ethnic groups and socioeconomic status (SES).
Methods. We examined the population discharged from any acute care hospital in Massachusetts and calculated rates of intensive care unit (ICU) stay by racial/ethnic and SES groups between April 26 and September 30, 2009. We used logistic regression models to identify predictors of ICU stay.
Results. Of 4874 H1N1-related hospitalizations, 526 (11%) were admitted to the ICU. Those in less affluent SES groups had lower risk of ICU stay than the most affluent SES group. Compared with Whites, Hispanics had significantly lower risk of 2009 H1N1-related ICU stay (odds ratio = 0.52; 95% confidence interval = 0.32, 0.86). Only 13% of Whites admitted to the ICU were in the lowest SES group, compared with 63% of Hispanics and 43% of Blacks.
Conclusions. To our knowledge, this is the first statewide description of 2009 H1N1 influenza-related ICU stays according to racial/ethnic group and SES in the United States. Future work should investigate evidence related to social determinants of health among racial/ethnic groups to reduce disparities in relation to pandemic influenza.
(Am J Public Health. Published online ahead of print November 14, 2013: e1-e8. doi:10.2105/AJPH.2013.301626).
Building an eScience Thesaurus for Librarians: A Collaboration Between the National Network of Libraries of Medicine, New England Region and an Associate Fellow at the National Library of Medicine
Objective: In response to the growing interest and adoption of eScience roles by librarians, those from the National Network of Libraries of Medicine, New England Region (NN/LM NER) and an Associate Fellow from the National Library of Medicine collaborated to build an eScience Thesaurus. The Thesaurus will introduce librarians to terminology and concepts in eScience, point to relevant literature and resources on data and digital research topics, and provide links to interviews with librarians and experts working in eScience-related roles. The eScience Thesaurus is a starting place for librarians to find the vocabulary to research the background, resources, and tools necessary for developing their capacity to provide eScience-related services.
Methods: The Associate Fellow completed a review of eScience-related literature to identify the seminal publications for the originations of these terms and concepts as they apply to libraries. Next, the Associate Fellow worked with the NN/LM NER to compile an environmental scan of resources that would be useful and applicable for librarians, and created a scope document and record structure. The team interviewed prominent librarians working in eScience roles and experts that have created digital tools and services used by the library community. Finally, the team sent the Thesaurus records out to five members of the advisory and editorial review boards from the eScience Portal for New England Librarians for evaluation.
Results: The eScience Thesaurus is now hosted on the eScience Portal for New England Librarians’ website. It provides a comprehensive list of more than 50 different terminologies and concepts, with links to seminal and relevant literature, resources, grants, and interviews on a variety of eScience-related topics.
Conclusion: The eScience Thesaurus is an evolving resource; as the field expands and more eScience-related terms are adopted by the library and information science community, the Portal will enable its users to electronically submit new vocabulary and records to the Thesuarus, thus preserving it as a go-to eScience resource for librarians.
Librarian involvement in the Open Access (OA) movement has traditionally focused on access to scholarly publications. Recent actions by the White House have focused attention on access on the data produced from federally sponsored research. Questions have emerged concerning access to the output of federally sponsored research and whether it is a public or private good. Understanding the political battle over access to federally funded research is closely tied to the ownership of the peer review process in higher education and associated revenue streams, and as a result, interest groups seeking to influence government regulation have politicized the issues. As a major funder of research in higher education, policies from the federal government are likely to drive change in research practices at higher education institutions and impact library services. The political economy of federally sponsored research data will shape research enterprises in higher education inspire a number of new services distributed throughout the research life cycle.
JESLIB Editor Elaine R. Martin introduces the articles in Volume 2, Issue 2 by discussing the evolving professional identity of embedded librarians. She proposes that it is time for the embedded librarian to push boundaries and move from a "bounded" professional to a "blended" professional.
Summary: Supplemental workbook for the Maintaining Independence and Sobriety through Systems Integration, Outreach, and Networking (MISSION) treatment approach, which was adapted specifically for Veterans (MISSION-VET). MISSION-VET, a flexible, integrated, time-limited, yet assertive service delivery platform was designed specifically to provide direct treatment, ongoing support, and care coordination to homeless Veterans suffering from co-occurring disorders and transitioning and/or adjusting to independent living in the community.
The Consumer Workbook is a supplemental workbook to engage homeless Veterans by providing exercises and resources to aid in their recovery from a co-occurring disorder and homelessness. Peer Support Specialists and Case Managers should work with the Veteran to complete the items in the workbook that correspond with specific Dual-Recovery Therapy sessions and use the workbook as a talking point in helping clients with co-occurring mental illness and substance abuse, homelessness and related issues that arise in the various stages of their recovery.
The Department of Housing and Urban Development – VA Supportive Housing (HUD-VASH) Program is a joint effort between HUD and VA to move Veterans and their families out of homelessness and into permanent housing. The HUD-VASH Resource Guide for Permanent Housing and Clinical Care was designed to provide case managers, and other who work with homeless Veterans in the HUD-VASH program, with a comprehensive set of resources to assist in addressing the multifaceted needs of homeless Veterans. The Resource Guide is a product of the National Center on Homelessness Among Veterans and was developed by a dynamic team of researchers, policy analysts, public health experts, psychologists, physicians and social workers located throughout the country.