Showing papers by "Jeffrey Bennett published in 2006"

The B cell response in multiple sclerosis

Abstract: Multiple sclerosis (MS) plaques and CSF contain increased amounts of intrathecally synthesized IgG, manifest as oligoclonal bands (OCBs) after protein electrophoresis. OCBs are not unique to MS and are also produced in infectious diseases of the CNS, in which the oligoclonal IgG has been shown to be antibody directed against the disease-causing agent. Thus, analysis of antibody specificity may identify the causative agent/antigen in MS. This review discusses recent studies that have analyzed the phenotypes of B cells in MS which infiltrate the CNS and the molecular features of their antigen-binding regions. Together with histologic studies showing the presence of ectopic lymphoid follicles in the meninges of some MS patients, this data supports the notion of a targeted and compartmentalized humoral response in MS.

Brainstem stereotactic biopsy sampling in children.

Abstract: Object Although it is widely accepted that biopsy sampling is not indicated for the diagnosis and empiric treatment of diffuse pontine glioma, it is common to encounter patients with brainstem lesions that cannot be diagnosed on the basis of imaging studies alone. In cases not amenable to resection, a tissue diagnosis may still be necessary to make appropriate treatment recommendations. The authors retrospectively reviewed their institutional experience with stereotactic biopsy procedures in pediatric patients during a 4-year period. Methods A three-dimensional graphics workstation was used for trajectory planning to obtain biopsy samples of brainstem lesions in 10 patients. One patient experienced mild diplopia postoperatively. No other morbidity was noted; no patient died as a result of the procedure. The biopsy procedure yielded a pathological diagnosis in all cases. A later resection in one patient resulted in a change in diagnosis. Overall, the pathological findings were varied, and in some cases the...

Choice modelling and the transfer of environmental values

Abstract: Benefit transfer is the practice of estimating economic values at a target site by utilizing the results of existing studies for different sites This text assesses the validity of benefit transfer using choice modeling in contrast to the traditional focus of transferring results from contingent valuation and travel cost models

Livelihood impacts of the conversion of cropland to forest and grassland program

Abstract: Land use changes induced by the Conversion of Cropland to Forest and Grassland Program are found to provide farm households sampled in four counties from Shaanxi and Qinghai Provinces with increased net profits. This result is found to be robust for a range of discount rates and output price projections. The net present value of the difference in farm profits with and without the Program is found to be positive even when payments made under the Program are subtracted from with Program profits. Variations in the impact of the Program on farm household net profits were observed across the county samples. These results suggest that reversion to pre-Program land uses is unlikely as long as farmer's rights over converted land are well defined and defended.

Natalizumab and progressive multifocal leukoencephalopathy: migrating towards safe adhesion molecule therapy in multiple sclerosis.

Abstract: Natalizumab, a humanized monoclonal antibody against alpha4beta1 integrin, was shown in clinical trials to dramatically reduce the relapse rate, development of new magnetic resonance imaging (MRI) lesions and progression of disability in patients with relapsing multiple sclerosis. Following its expedited approval, sales of the drug were discontinued owing to the emergence of two cases of progressive multifocal leukoencephalopathy (PML), a rare but deadly viral infection of the central nervous system (CNS) associated with immunosuppression. Owing to the effect of natalizumab on central nervous system leukocyte recruitment, the emergence of PML has been attributed to diminished immunosurveillance. The lack of additional opportunistic or CNS infections among natalizumab-treated patients, however, suggests that alternate mechanisms may contribute to the infectious risk. This review examines how the inhibition of alpha4beta1-mediated adhesion might establish a unique milieu for the development of PML and how future approaches to selective adhesion molecule therapy in multiple sclerosis might avoid a similar fate.

Identification of fibers at risk for degeneration by diffusion tractography in patients at high risk for MS after a clinically isolated syndrome.

Abstract: Purpose Focal inflammatory/demyelinating lesions are thought to be the source of Wallerian degeneration or other injury to local, transiting fiber tracts in the brain or spinal cord in multiple sclerosis (MS). A methodology is established to isolate connections between focal demyelinating lesions and intersecting fibers to permit explicit analyses of the pathology of secondary fiber injury distant from the focal lesion. Materials and Methods A strategy is described and feasibility demonstrated in three patients with a clinically isolated syndrome and positive MRI (at high risk for MS). The strategy utilizes streamtube diffusion tractography to identify neuronal fibers that intersect a focal lesion and pass through a region of interest, in this case the corpus callosum, where distal (to focal lesion) interrogation can be accomplished. Results A sizeable fraction of the normal appearing white matter (NAWM) in the early stages of disease can be defined in the corpus callosum, which is distinctive in that this tissue connects to distant demyelinating lesions. Conclusion The new class of tissue called fibers-at-risk for degeneration (FAR) can be identified and interrogated by a variety of quantitative MRI methodologies to better understand neuronal degeneration in MS. J. Magn. Reson. Imaging 2006. Published 2006 Wiley-Liss, Inc.

Screening Random Peptide Libraries with Subacute Sclerosing Panencephalitis Brain-Derived Recombinant Antibodies Identifies Multiple Epitopes in the C-Terminal Region of the Measles Virus Nucleocapsid Protein

Abstract: Infectious and inflammatory diseases of the CNS are often characterized by a robust B-cell response that manifests as increased intrathecal immunoglobulin G (IgG) synthesis and the presence of oligoclonal bands We previously used laser capture microdissection and single-cell PCR to analyze the IgG variable regions of plasma cells from the brain of a patient with subacute sclerosing panencephalitis (SSPE) Five of eight human IgG1 recombinant antibodies (rAbs) derived from SSPE brain plasma cell clones recognized the measles virus (MV) nucleocapsid protein, confirming that the antibody response in SSPE targets primarily the agent causing disease In this study, as part of our work on antigen identification, we used four rAbs to probe a random phage-displayed peptide library to determine if epitopes within the MV nucleocapsid protein could be identified with SSPE brain rAbs All four of the SSPE rAbs enriched phage-displayed peptide sequences that reacted specifically to their panning rAb by enzyme-linked immunosorbent assay BLASTP searches of the NCBI protein database revealed clear homologies in three peptides and different amino acid stretches within the 65 C-terminal amino acids of the MV nucleocapsid protein The specificities of SSPE rAbs to these regions of the MV nucleocapsid protein were confirmed by binding to synthetic peptides or to short cDNA expression products These results indicate the feasibility of using peptide screening for antigen discovery in central nervous system inflammatory diseases of unknown etiology, such as multiple sclerosis, neurosarcoidosis, or Behcet's syndrome

An integrated approach for modelling the impacts of land and water resource use in the Dak Lak plateau, Viet Nam

Abstract: This paper describes an integrated approach developed to model the physical and related social welfare impacts of alternative water allocations in the Dak Lak plateau, Viet Nam. A physically based, distributed and integrated model of the plateau’s surface and groundwater resources has been developed. This model distributively links hydrodynamics and water use decisions, in particular how the plateau’s hydrology responds to different spatial configurations of cropping patterns, crop water allocations and urban water use. The outputs of this model will be compartmentally linked to economic modelling work in order to simulate distributive welfare outcomes resulting from different water allocation decisions over the short to medium term. The welfare impacts of alternative water allocations are being assessed for three “goods” – agricultural production, urban and environmental – using both revealed and stated preference approaches. This paper is a progress report on this modelling effort, detailing the objectives, approach and integration methodology and including discussion of some results to date.

Valuing Australian cultural institutions: developing a cultural worldview scale

Abstract: This paper explores the relationship between cultural attitudes and estimates of the economic value of cultural institutions. The relationship is tested with preliminary findings from an empirical study of the economic value of two national cultural institutions in Australia?the National Museum of Australia and Old Parliament House (the historic former national parliament building). The two institutions are the subject of separate choice modelling surveys aimed at estimating their economic value. An innovative element of the study is the development of a cultural worldview (CW) scale, similar in concept to the new ecological paradigm scale, to measure the latent characteristics of respondents. The study enables the testing of relationships between the CW scale, socio-demographic variables, and the stated economic values.

Estimating intergenerational distribution preferences using choice modelling

Abstract: Resource management decisions influence not only the output of the economy but also the distribution of utility between groups within the community. The theory of Cost Benefit Analysis provides a means of incorporating distributional changes into the decision making calculus through the application of distributional or welfare weights. This paper reports the results of research designed to estimate distributional weights suitable for inclusion in a Cost Benefit Analysis framework. The findings of a choice modelling experiment designed to estimate community preferences with respect to intergenerational utility distribution are presented.

Estimating intergenerational utility distribution preferences

Abstract: Resource management decisions influence not only the output of the economy but also the distribution of utility between groups within the community. The theory of Benefit Cost Analysis provides a means of incorporating this distributional change through the application of distributional or welfare weights. This paper reports the results of research designed to estimate distributional weights suitable for inclusion in a Benefit Cost Analysis framework. The findings of a choice modelling experiment estimating community preferences with respect to intergenerational utility distribution are presented to illustrate this innovative application of a stated preference technique.

A Critique of Conventional Non-market Valuation: Attitudes and Action

Abstract: This paper revisits two conventional beliefs of environmental nonmarket valuation and examines their weaknesses and a new opportunity. The two beliefs are that willingness to pay (WTP) is an appropriate measure of non-market behaviour and that exogenous variables are relevant predictors of WTP whilst endogenous variables are not. The contemporary literature in psychology and economics is reviewed to demonstrate departures from these two beliefs.

A Critique of Conventional Non-market Valuation: Attitudes and Action

Abstract: This paper revisits two conventional beliefs of environmental nonmarket valuation and examines their weaknesses and a new opportunity. The two beliefs are that willingness to pay (WTP) is an appropriate measure of non-market behaviour and that exogenous variables are relevant predictors of WTP whilst endogenous variables are not. The contemporary literature in psychology and economics is reviewed to demonstrate departures from these two beliefs.