The Next Generation of Market-Based Environmental Policies

We examine what will be required if market-based environmental policy instruments are to become a major force in U.S. environmental policy. We define market-based instruments, and specify five categories: pollution charges; tradable permits; deposit refund systems; reducing market barriers; and eliminating government subsidies. We review major U.S. applications, including: EPA's emissions trading program; the leaded gasoline phasedown; water quality permit trading; CFC trading; SO2 allowance trading; and the RECLAIM program. We assess the U.S. experience in terms of the relatively limited use of these instruments and in terms of the mixed record of performance of implemented instruments. We ask how the next generation of market-based instruments can be advanced, focusing on four sets of approaches: improving program design; applying market-based instruments on the state level; implementing new Federal programs; and addressing long-term issues. We conclude with a brief prognosis of the likely future role of market-based instruments in U.S. environmental policy.

Laboratory studies of stratified convection with multiple states

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier Ltd for personal use, not for redistribution. The definitive version was published in Ocean Modelling 11 (2006): 333-346, doi:10.1016/j.ocemod.2005.01.002.A simplified box model of the cooling of a salt-stratified ocean has been constructed in the laboratory to test a theory that predicts multiple equilibria if certain conditions exist. An isothermal basin of water had a thin layer of fresh water over salt water. Beside this was a smaller basin connected to the large basin by horizontal tubes at the top, middle and bottom. The small basin was cooled from above. If the top tube has more flow resistance than the bottom tubes, theory indicates that as cooling temperature T* is made colder, there is a sudden transition between two flow states. The velocities in the tubes jump to greater values, while salinity and temperature in the small basin jump to another value. These multiple states are found in the laboratory experiments along with some states that oscillate. Laboratory measurements and layered model calculations for hysteresis and the jump of temperature and salinity agree qualitatively, but there is only rough quantitative agreement.The National Science Foundation, Physical Oceanography Section under Grant OCE-0081179 supported the experimental laboratory studies

Maturation of neuron types in nucleus of solitary tract associated with functional convergence during development of taste circuits

Late fetal through postnatal development in sheep is a period of increasing convergence of afferent taste fibers onto second-order neurons in the nucleus of the solitary tract (NST). To learn whether neuron morphology alters in concert with convergence and neurophysiological development in NST, three-dimensional neuron reconstructions were made of cells in a functionally defined region of gustatory NST from Golgi preparations of the brainstem. Elongate, multipolar, and ovoid neurons were studied in fetuses from 85 days of gestation through the perinatal period (term = 147 days of gestation), to postnatal stages. Somal size and form, and dendritic complexity and extent, increased markedly from 85 to about 110 days of gestation in both of the proposed NST projection neurons, elongate and multipolar. From 130 days of gestation to postnatal ages, growth of dendrites of elongate neurons plateaued or declined, whereas dendrites of multipolar neurons apparently continued to increase in size and extent. In addition, spine density decreased on elongate neurons but remained stable on multipolar neurons. Morphological variables of ovoid cells, proposed interneurons in NST, did not alter over this later period. The data suggest that multipolar, not elongate or ovoid, neurons are logical candidates to receive the increasing afferent fiber input onto NST cells during late gestation. Also, neural activity from taste afferent fibers is more likely to have a role in altering NST neuron morphology at later, rather than earlier, developmental periods. © 1994 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50062/1/903450304_ftp.pd

Assessment of novel therapeutics and development of monoclonal antibody targeting moieties for drug delivery systems in the treatment of osteoarthritis

In Part 1 of this work ex vivo models of cytokine induced cartilage degradation were developed and extensively characterised for the subsequent assessment of Surfen, a heparan sulphate antagonist as a potential therapeutic for the treatment of osteoarthritis (OA). Cell signalling pathway analysis revealed synergistic activation of the stress-activated protein kinase (SAPK/JNK) pathway mediated by interleukin-1 alpha (IL-1a) + Oncostatin M (OSM) compared to either cytokine alone. Pharmacological inhibition confirmed the role of SAPK/JNK in catabolic gene expression and cartilage matrix degradation. Analysis of cartilage oligomeric matrix degradation (COMP) in cartilage in response to cytokines identified a role for ADAMTS-4 in COMP degradation. Surfen is a known inhibitor of anthrax lethal factor metalloproteinase. This Thesis identified Surfen as a direct inhibitor of ADAMTS-4 and furin, a pro-protein convertase involved in ADAMTS activation. Surfen inhibited glycosaminoglycan (GAG) loss and aggrecanase activity in IL-1a but not IL-1a+OSM treated cartilage explants. Gene expression studies showed Surfen (7 μM) attenuated IL-1a and IL-1a+OSM mediated increases in catabolic gene expression, however, increased Surfen concentration (15 μM) resulted in increased ADAMTS-4 expression and activity in IL-1a+OSM conditions that likely precludes the use of Surfen as an OA therapy. Targeting of sustained release drug delivery systems (DDS) to specific tissues within the joint could increase retention whilst reducing off-target effects. In Part 2 lubricin was identified as a candidate cartilage surface target. Conjugation of anti-lubricin mAb to DDS improved binding and retention in ex vivo studies. For the targeting of pro-inflammatory M1 subtype macrophages in the synovium, novel mAbs were developed to target human and murine FcgRI/CD64. Assessment of mIgG1 and mIgG2a anti-FcgRI/CD64 binding revealed species and isotype specific differences in non-specific binding to monocyte cell lines, whereas no non-specifc binding of mIgM was observed suggesting in these subtypes are preferential in the specifc targeting of FcgRI/CD64. Combined, this Thesis has assesed the potential of a novel therapeutic and developed novel joint targeting strategies for treatment of OA

Fluorescent Labeling of Helminth Extracellular Vesicles Using an In Vivo Whole Organism Approach

In the last two decades, extracellular vesicles (EVs) from the three domains of life, Archaea, Bacteria and Eukaryotes, have gained increasing scientific attention. As such, the role of EVs in host-pathogen communication and immune modulation are being intensely investigated. Pivotal to EV research is the determination of how and where EVs are taken up by recipient cells and organs in vivo, which requires suitable tracking strategies including labelling. Labelling of EVs is often performed post-isolation which increases risks of non-specific labelling and the introduction of labelling artefacts. Here we exploited the inability of helminths to de novo synthesise fatty acids to enable labelling of EVs by whole organism uptake of fluorescent lipid analogues and the subsequent incorporation in EVs. We showed uptake of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (DOPE-Rho) in Anisakis spp. and Trichuris suis larvae. EVs isolated from the supernatant of Anisakis spp. labelled with DOPE-Rho were characterised to assess the effects of labelling on size, structure and fluorescence of EVs. Fluorescent EVs were successfully taken up by the human macrophage cell line THP-1. This study, therefore, presents a novel staining method that can be utilized by the EV field in parasitology and potentially across multiple species

Service User Perspectives on Engagement in an Occupational Therapy-Led Pulmonary Rehabilitation Programme: A Qualitative Interview Study

Introduction: Pulmonary rehabilitation (PR) is an intervention for people with chronic respiratory conditions. There are questions about which components are important to its success, including the nature of occupational therapy involvement. The aim of this research was to explore the experiences of people who had attended an occupational therapy-led PR programme in the United Kingdom to determine the most important components.Method: Semi-structured telephone interviews were conducted with service users who had experience of a community based PR programme. Interviews were transcribed verbatim. Data were analysed using the framework analysis method with three researchers contributing to the analysis. Findings: Nine people took part in the interviews, with a mean age of 72 years. Four themes were identified which were organised around the concepts of Doing, Being, Becoming Belonging. These were ‘Doing exercise and physical activity’, ‘being breathless’, ‘belonging as an individual within the group’ and ‘becoming a person who lives with COPD’. Conclusion: Doing physical activity, whilst coping with being breathless and belonging as an individual within a group can positively influence experiences and perceived outcomes during and after PR. These dimensions have the potential to shape occupation-focussed PR programmes and the occupational therapy contribution in this area of practice

Cost-benefit analysis of extending support to domestic abuse victims with NRPF: a technical report for the Domestic Abuse Commissioner

This report provides the technical underpinning to the report by the Domestic Abuse Commissioner’s Report1 laid before Parliament in December 2022. That report was in response to the Home Office request that she set out ‘the gaps in evidence available to the Home Office on support for Migrant Victims of Domestic Abuse, by establishing the number of victims and survivors of domestic abuse who have no recourse to public funds, the cost of supporting those who need support, and the cost benefit of such interventions.2’ LSE was asked by the Commissioner to provide a detailed technical analysis to underpin her response. This LSE report provides our views on relevant evidence but no policy recommendations. Such recommendations are made in the Commissioner’s report, having considered our evidence alongside the evidence of other stakeholders and people she has consulted. Our analysis required us to make strong assumptions, and there is significant uncertainty around many of them. There is considerable uncertainty in published validated statistics about the numbers of migrants in the UK with each visa status, and even more uncertainty about numbers of undocumented migrants and of ‘visitors’. There is also uncertainty about how many of these migrants currently experience domestic abuse, and an added and independent uncertainty about the proportion of those people who would present at services. We have also had to make various assumptions which affect the costs and benefits. We address and mitigate these and other uncertainties through our sensitivity analysis and additional modelling in this report. In addition, an accompanying Excel workbook sets out in detail our assumptions and how they underpin our conclusions, which allows for further sensitivity analysis and modelling to be done

Ultrastructure of primary afferent terminals and synapses in the rat nucleus of the solitary tract: Comparison among the greater superficial petrosal, chorda tympani, and glossopharyngeal nerves

The greater superficial petrosal (GSP), chorda tympani (CT), and glossopharyngeal (IX) nerves terminate in overlapping patterns in the brainstem in the rat nucleus of the solitary tract (NTS). There is one region, in particular, that receives overlapping inputs from all three nerves and is especially plastic during normal and experimentally altered development. To provide the requisite data necessary ultimately to delineate the circuitry in this region, we characterized the morphology of the synaptic inputs provided by the GSP, CT, and IX nerves through transmission electron microscopy. Although all three nerves had features characteristic of excitatory nerve terminals, ultrastructural analysis revealed dimorphic morphologies differentiating IX terminals from GSP and CT terminals. IX terminals had a larger area than GSP and CT terminals, and more synapses were associated with IX terminals compared with GSP and CT terminals. Additionally, IX terminals formed synapses most often with spines, as opposed to GSP and CT terminals, which formed synapses more often with dendrites. IX terminals also exhibited morphological features often associated with synaptic plasticity more often than was seen for GSP and CT terminals. These normative data form the basis for future studies of developmentally and environmentally induced plasticity in the rodent brainstem. J. Comp. Neurol. 502:1066–1078, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55995/1/21371_ftp.pd