New Results on Context-Free Tree Languages

Context-free tree languages play an important role in algebraic semantics and are applied in mathematical linguistics. In this thesis, we present some new results on context-free tree languages

Education in action : educating USNORTHCOM's critical stakeholders at the Away Game

CHDS State/LocalTraining Team, educating key stakeholder personnel at their location. After providing background on the United States Northern Command (NORTHCOM) and discussing why it is important for stakeholders to have an understanding of the unit's missions, organizations, capabilities and limitations, the thesis poses a research question: "How can NORTHCOM change its outreach and education policies and practices to more effectively educate its key interagency stakeholders, at the stakeholder location, in order to improve response efforts during a crisis?" Stakeholders are identified ("WHO to Educate"), a customizable education package is presented ("WHAT to Educate"), several delivery options are discussed ("HOW to Educate"), and several courses of action are considered regarding Educator Options ("WHO Should Educate"). A methodology called the Military Decision Making Process (MDMP) is utilized to assist in identifying the most effective courses of action, developing evaluation criteria, ranking each course of action utilizing those criteria, and using a quantifiable system to determine the most effective courses of action. These chapters are augmented with a discussion on developing and implementing measures of effectiveness, along with recommended areas for future study.http://archive.org/details/educationinction109453957Major, Command Briefer, U.S. Northern Command (USNORAD/NORTHCOM) Commanders Action Group, author

Development and Implementation of a Pharmacist-managed Outpatient Parenteral Antimicrobial Therapy Program

Purpose The development and implementation of a pharmacist-managed outpatient parenteral antimicrobial therapy (OPAT) program in a county teaching hospital are described. Summary A pharmacist-managed OPAT program was developed and implemented at a county teaching hospital to provide consistent evaluation, approval, and monitoring of patients requiring OPAT for the treatment of infection. The developmental and implementation stages of the OPAT program included (1) a needs assessment, (2) the identification of resources necessary for program operation, (3) delineation of general OPAT program operations and activities of individual OPAT clinicians, (4) the development of patient selection criteria, including a plan of care algorithm, and (5) acquisition of administrative support to approve the program. In this program, the OPAT pharmacist plays an integral role in the management and oversight of OPAT patients, working under a collaborative agreement with infectious diseases physicians. The OPAT pharmacist assists with appropriate patient and regimen selection, confirmation of orders on discharge, assuring that laboratory tests for safety surveillance are performed and evaluated, performing routine monitoring for adverse events and line complications, and assuring the removal of the vascular access device upon the completion of OPAT. Conclusion: The OPAT program provides structured monitoring, patient follow-up, and led to improvements in patient outcome with minimization of treatment and line-related adverse events

Should histoplasmosis be screened for before initiation of tumour necrosis factor alpha inhibitors?

Histoplasmosis is a soil based dimorphic fungus endemic to the Midwest and Southeastern United States and is responsible for infection through inhalation of conidia. Infection is usually asymptomatic, as the fungal growth is contained by formation of granulomas. However, dissemination can occur in immunocompromised hosts due to the lack of optimal activity of interferon gamma, tumor necrosis factor-alpha (TNF-alpha) and interleukin-17. There is a significant overlap between the symptomatology of histoplasmosis and granulomatosis with polyangiitis (GPA). We are reporting a case of a 48-year-old female who presented with high grade fever, worsening generalized weakness and tachycardia. She had a previous history of bilateral cavitary lung lesions for which she was evaluated at an outside facility. As her entire infectious work up was negative and found to be positive for antineutrophil cytoplasmic antibody (ANCA), a diagnosis of GPA was made and she was initiated on rituximab infusions 7 weeks prior to her presentation to our facility. Repeat infectious work up at our facility was positive for (1,3) beta-D-glucan test and urine histoplasma antigen. Prompt discontinuation of rituximab and initiation of systemic antifungal therapy led to clinical improvement. Based on this experience we would like to highlight the association of histoplasma with ANCA positivity along with the importance of closely monitoring these patients, for possible clinical worsening after the initiation of immunosuppressive therapy, despite the negative infectious work up

Immune reconstitution inflammatory syndrome in AIDS patient after successful induction of virological suppression with cabotegravir/rilpivirine

Long-acting (LA) cabotegravir/rilpivirine (CAB/RPV) is a complete regimen for the management of human immunodeficiency virus type 1 (HIV-1) infection to replace their oral antiretroviral therapy (ART) when they have been virologically suppressed. We present a case of successful achievement of undetectable HIV RNA viral load levels in an acquired immunodeficiency syndrome (AIDS) patient with long-standing virologic failure within two months of CAB/RPV LA initiation. This was later complicated by immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium-intracellulare (MAI) infection and hepatitis B virus (HBV) reactivation

Genetic Modification of Human Peripheral Blood Lymphocytes with a Transdominant Negative Form of Rev: Safety and Toxicity

Overview summary Expression of Rev M10, a transdominant mutant form of the Rev gene, in T cell lines confers resistance to HIV in vitro. Isertion of this Rev M10 gene into PBL appears to be nontoxic and well-tolerated by SCID mice. These results demonstrate that genetic modification of T cells by an antiviral gene can be performed safely and without overt toxicity. This finding encourages the development of therapeutic strategies to genetically protect T cells to prolong their survival in HIV-infected individuals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63234/1/hum.1995.6.8-997.pd

Virulence Factors Identified by Cryptococcus neoformans Mutant Screen Differentially Modulate Lung Immune Responses and Brain Dissemination

Deletions of cryptococcal PIK1, RUB1, and ENA1 genes independently rendered defects in yeast survival in human CSF and within macrophages. We evaluated virulence potential of these genes by comparing wild-type Cryptococcus neoformans strain H99 with deletant and complement strains in a BALB/c mouse model of pulmonary infection. Survival of infected mice; pulmonary cryptococcal growth and pathology; immunological parameters; dissemination kinetics; and CNS pathology were examined. Deletion of each PIK1, RUB1, and ENA1 differentially reduced pulmonary growth and dissemination rates of C. neoformans and extended mice survival. Furthermore, pik1Δ induced similar pathologies to H99, however, with significantly delayed onset; rub1Δ was more efficiently contained within pulmonary macrophages and was further delayed in causing CNS dissemination/pathology; whereas ena1Δ was progressively eliminated from the lungs and did not induce pathological lesions or disseminate into the CNS. The diminished virulence of mutant strains was associated with differential modulation of pulmonary immune responses, including changes in leukocyte subsets, cytokine responses, and macrophage activation status. Compared to H99 infection, mutants induced more hallmarks of a protective Th1 immune response, rather than Th2, and more classical, rather than alternative, macrophage activation. The magnitude of immunological effects precisely corresponded to the level of virulence displayed by each strain. Thus, cryptococcal PIK1, RUB1, and ENA1 differentially contribute to cryptococcal virulence, in correlation with their differential capacity to modulate immune responses

Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous Structure, by Cryptococcus neoformans Promotes Alternative Activation of Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2 Bias

Macrophage receptor with collagenous structure (MARCO) contributes to fungal containment during the early/innate phase of cryptococcal infection; however, its role in adaptive antifungal immunity remains unknown. Using a murine model of cryptococcosis, we compared host adaptive immune responses in wild-type and MARCO−/− mice throughout an extended time course post-infection. Unlike in early infection, MARCO deficiency resulted in improved pulmonary fungal clearance and diminished cryptococcal dissemination during the efferent phase. Improved fungal control in the absence of MARCO expression was associated with enhanced hallmarks of protective Th1-immunity, including higher frequency of pulmonary TNF-α-producing T cells, increased cryptococcal-antigen-triggered IFN-γ and TNF-α production by splenocytes, and enhanced expression of M1 polarization genes by pulmonary macrophages. Concurrently, we found lower frequencies of IL-5- and IL-13-producing T cells in the lungs, impaired production of IL-4 and IL-10 by cryptococcal antigen-pulsed splenocytes, and diminished serum IgE, which were hallmarks of profoundly suppressed efferent Th2 responses in MARCO-deficient mice compared to WT mice. Mechanistically, we found that MARCO expression facilitated early accumulation and alternative activation of CD11b+ conventional DC (cDC) in the lung-associated lymph nodes (LALNs), which contributed to the progressive shift of the immune response from Th1 toward Th2 at the priming site (LALNs) and local infection site (lungs) during the efferent phase of cryptococcal infection. Taken together, our study shows that MARCO can be exploited by the fungal pathogen to promote accumulation and alternative activation of CD11b+ cDC in the LALN, which in turn alters Th1/Th2 balance to promote fungal persistence and dissemination