Characterization of IgA response among women with incident HPV 16 infection

AbstractPrevious studies have characterized the prevalence and duration of serum IgG antibodies to human papillomavirus type 16 (HPV 16) in a well-studied cohort of college women, using viruslike particle- (VLP) based ELISAs. In this study IgA antibodies in cervical secretions and sera were examined using a newly developed capsomer-based ELISA and the patterns observed for serum IgG, serum IgA, and cervical IgA antibodies were compared. The median time to antibody detection from the first detection of HPV 16 DNA was 10.5 months for IgA in cervical secretions and 19.1 months for serum IgA. Serum IgA antibody conversion was observed less frequently and occurred later than IgA conversion in cervical secretions (P = 0.011) or serum IgG conversion (P = 0.051). The median time to antibody reversion, following seroconversion, was 12.0 months for IgA in cervical secretions and 13.6 months for serum IgA, whereas approximately 20% of women with serum IgG antibodies reverted within 36 months. Thus, the duration of IgA in cervical secretions and sera was shorter than the duration of serum IgG (P = 0.007 and 0.001)

Simulating the global distribution of nitrogen isotopes in the ocean

We present a new nitrogen isotope model incorporated into the three-dimensional ocean component of a global Earth system climate model designed for millennial timescale simulations. The model includes prognostic tracers for the two stable nitrogen isotopes, 14N and 15N, in the nitrate (NO3−), phytoplankton, zooplankton, and detritus variables of the marine ecosystem model. The isotope effects of algal NO3− uptake, nitrogen fixation, water column denitrification, and zooplankton excretion are considered as well as the removal of NO3− by sedimentary denitrification. A global database of δ15NO3− observations is compiled from previous studies and compared to the model results on a regional basis where sufficient observations exist. The model is able to qualitatively and quantitatively reproduce many of the observed patterns such as high subsurface values in water column denitrification zones and the meridional and vertical gradients in the Southern Ocean. The observed pronounced subsurface minimum in the Atlantic is underestimated by the model presumably owing to too little simulated nitrogen fixation there. Sensitivity experiments reveal that algal NO3− uptake, nitrogen fixation, and water column denitrification have the strongest effects on the simulated distribution of nitrogen isotopes, whereas the effect from zooplankton excretion is weaker. Both water column and sedimentary denitrification also have important indirect effects on the nitrogen isotope distribution by reducing the fixed nitrogen inventory, which creates an ecological niche for nitrogen fixers and, thus, stimulates additional N2 fixation in the model. Important model deficiencies are identified, and strategies for future improvement and possibilities for model application are outlined

A model to guide development and application of multiple nursing theories

Over the past decade there has been an explosion of interest and activity in the nursing profession directed toward the development of a theory base for nursing education and practice. Although we support the overall thrust of nursing theory development, we have concerns about its utility, scope and stated purposes. We are especially sensitive to the plight of the practising nurse who might attempt to use the current nursing theories to guide and explain choices made in daily practice. In this paper we examine current use of the word 'theory' and describe problems inherent in nursing's efforts to apply educationally derived conceptual frameworks to nursing practice. We identify a need for the development and use of many theories for nursing and argue that there is a logical need for a 'meta-model' which will guide the use of multiple theories in practice. A model is presented which allows the practising nurse to examine the various theories in terms of their applicability to a given client situation. We believe the model is also useful to nurse educators and researchers who may be attempting to use nursing theories for educational purposes or develop nursing's knowledge base through empirical work

Association of NMT2 with the acyl-CoA carrier ACBD6 protects the N-myristoyltransferase reaction from palmitoyl-CoA[S]

The covalent attachment of a 14-carbon aliphatic tail on a glycine residue of nascent translated peptide chains is catalyzed in human cells by two N-myristoyltransferase (NMT) enzymes using the rare myristoyl-CoA (C(14)-CoA) molecule as fatty acid donor. Although, NMT enzymes can only transfer a myristate group, they lack specificity for C(14)-CoA and can also bind the far more abundant palmitoyl-CoA (C(16)-CoA) molecule. We determined that the acyl-CoA binding protein, acyl-CoA binding domain (ACBD)6, stimulated the NMT reaction of NMT2. This stimulatory effect required interaction between ACBD6 and NMT2, and was enhanced by binding of ACBD6 to its ligand, C(18:2)-CoA. ACBD6 also interacted with the second human NMT enzyme, NMT1. The presence of ACBD6 prevented competition of the NMT reaction by C(16)-CoA. Mutants of ACBD6 that were either deficient in ligand binding to the N-terminal ACBD or unable to interact with NMT2 did not stimulate activity of NMT2, nor could they protect the enzyme from utilizing the competitor C(16)-CoA. These results indicate that ACBD6 can locally sequester C(16)-CoA and prevent its access to the enzyme binding site via interaction with NMT2. Thus, the ligand binding properties of the NMT/ACBD6 complex can explain how the NMT reaction can proceed in the presence of the very abundant competitive substrate, C(16)-CoA

Modeling Hepatitis C treatment policy.

Chronic infection with Hepatitis C virus (HCV) results in cirrhosis, liver cancer and death. As the nation's largest provider of care for HCV, US Veterans Health Administration (VHA) invests extensive resources in the diagnosis and treatment of the disease. This report documents modeling and analysis of HCV treatment dynamics performed for the VHA aimed at improving service delivery efficiency. System dynamics modeling of disease treatment demonstrated the benefits of early detection and the role of comorbidities in disease progress and patient mortality. Preliminary modeling showed that adherence to rigorous treatment protocols is a primary determinant of treatment success. In depth meta-analysis revealed correlations of adherence and various psycho-social factors. This initial meta-analysis indicates areas where substantial improvement in patient outcomes can potentially result from VA programs which incorporate these factors into their design

Modeling Hepatitis C treatment policy.

Chronic infection with Hepatitis C virus (HCV) results in cirrhosis, liver cancer and death. As the nation's largest provider of care for HCV, US Veterans Health Administration (VHA) invests extensive resources in the diagnosis and treatment of the disease. This report documents modeling and analysis of HCV treatment dynamics performed for the VHA aimed at improving service delivery efficiency. System dynamics modeling of disease treatment demonstrated the benefits of early detection and the role of comorbidities in disease progress and patient mortality. Preliminary modeling showed that adherence to rigorous treatment protocols is a primary determinant of treatment success. In depth meta-analysis revealed correlations of adherence and various psycho-social factors. This initial meta-analysis indicates areas where substantial improvement in patient outcomes can potentially result from VA programs which incorporate these factors into their design

Outpatient Upper Respiratory Tract Viral Infections in Children with Malaria Symptoms in Western Kenya

A cross-sectional study was performed in children 5 through 10 years of age presenting to outpatient clinics in Nyanza Province, Kenya, in which nasal swab and blood specimens were collected during the high malaria transmission season. Patients presenting with malaria-like symptoms within 4 days of fever onset were enrolled in the study. Plasmodium parasitemia was determined by blood smear microscopy. Nasal swabs were screened for a panel of respiratory viruses by polymerase chain reaction. Influenza A, rhinoviruses, and other respiratory viruses were detected in 18%, 26%, and 12% of 197 specimens, respectively. Four of 36 patients with influenza A had a positive malaria blood slide, compared with 20 of 52 patients with rhinovirus. A significant burden of disease caused by influenza A in febrile children during the study period was observed, highlighting the need for further research into the burden of influenza disease in regions where malaria is holoendemic