Environmental Biosciences Program Fourth Quarter Report

In May 2002, the United States Department of Energy (DOE) signed Assistance Instrument Number DE-FC09-02CH11109 with the Medical University of South Carolina (MUSC) to support the Environmental Biosciences Program (EBP). This funding instrument replaces DOE Assistance Instrument Number DE-FC02-98CH10902. EBP is an integrated, multidisciplinary scientific program, employing a range of research initiatives to identify, study and resolve environmental health risk issues. These initiatives are consistent with the Medical University's role as a comprehensive state-supported health sciences institution and the nation's need for new and better approaches to the solution of a complex and expansive array of environment-related health problems. The intrinsic capabilities of a comprehensive health sciences institution enable the Medical University to be a national resource for the scientific investigation of environmental health issues. EBP's success in convening worldwide scientific expertise is due in part to the inherent credibility the Medical University brings to the process of addressing these complex issues

Application of Cryopreserved Human Hepatocytes in Trichloroethylene Risk Assessment: Relative Disposition of Chloral Hydrate to Trichloroacetate and Trichloroethanol

BACKGROUND: Trichloroethylene (TCE) is a suspected human carcinogen and a common ground-water contaminant. Chloral hydrate (CH) is the major metabolite of TCE formed in the liver by cytochrome P450 2E1. CH is metabolized to the hepatocarcinogen trichloroacetate (TCA) by aldehyde dehydrogenase (ALDH) and to the noncarcinogenic metabolite trichloroethanol (TCOH) by alcohol dehydrogenase (ADH). ALDH and ADH are polymorphic in humans, and these polymorphisms are known to affect the elimination of ethanol. It is therefore possible that polymorphisms in CH metabolism will yield subpopulations with greater than expected TCA formation with associated enhanced risk of liver tumors after TCE exposure. METHODS: The present studies were undertaken to determine the feasibility of using commercially available, cryogenically preserved human hepatocytes to determine simultaneously the kinetics of CH metabolism and ALDH/ADH genotype. Thirteen human hepatocyte samples were examined. Linear reciprocal plots were obtained for 11 ADH and 12 ALDH determinations. RESULTS: There was large interindividual variation in the V(max) values for both TCOH and TCA formation. Within this limited sample size, no correlation with ADH/ALDH genotype was apparent. Despite the large variation in V(max) values among individuals, disposition of CH into the two competing pathways was relatively constant. CONCLUSIONS: These data support the use of cryopreserved human hepatocytes as an experimental system to generate metabolic and genomic information for incorporation into TCE cancer risk assessment models. The data are discussed with regard to cellular factors, other than genotype, that may contribute to the observed variability in metabolism of CH in human liver

The Qualitative Method of Impact Analysis

Consider the qualitative approach to evaluation design (as opposed to measurement) to be typified by a case study with a sample of just one. Although there have certainly been elaborate and emphatic defenses of the qualitative approach to program evaluation, such defenses rarely attempt to qualify the approach explicitly and rigorously as a method of impact analysis. The present paper makes that attempt. The problem with seeking to advance a qualitative method of impact analysis is that impact is a matter of causation and a non-quantitative approach to design is apparently not well suited to the task of establishing causal relations. The root of the difficulty is located in the counterfactual definition of causality, which is our only broadly accepted formal definition of causality for social science. It is not, however, the only definition we use informally. Another definition, labeled “physical causality,” is widely used in practice and has recently been formalized. Physical causality can be applied to the present problem. For example, it explains the persuasiveness of Striven’s “Modus Operandi” approach tailored case study design with a sample size of one in principle as strong a basis for making inferences program impact as a randomized experiment. Crucial program evaluation finding that people’s “operative reasons” for doing what they do are the physical actions. it is shown that external validity using this qualitative approach would have exceptional strengths.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67113/2/10.1177_109821409902000106.pd

Mindfulness based interventions in multiple sclerosis: a systematic review

<b>Background</b> Multiple sclerosis (MS) is a stressful condition; depression, anxiety, pain and fatigue are all common problems. Mindfulness based interventions (MBIs) mitigate stress and prevent relapse in depression and are increasingly being used in healthcare. However, there are currently no systematic reviews of MBIs in people with MS. This review aims to evaluate the effectiveness of MBIs in people with MS.<p></p> <b>Methods</b> Systematic searches were carried out in seven major databases, using both subject headings and key words. Papers were screened, data extracted, quality appraised, and analysed by two reviewers independently, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Perceived stress was the primary outcome. Secondary outcomes include mental health, physical health, quality of life, and health service utilisation. Statistical meta-analysis was not possible. Disagreements were adjudicated by a third party reviewer.<p></p> <b>Results</b> Three studies (n = 183 participants) were included in the final analysis. The studies were undertaken in Wales (n = 16, randomised controlled trial - (RCT)), Switzerland (n = 150, RCT), and the United States (n = 17, controlled trial). 146 (80%) participants were female; mean age (SD) was 48.6 (9.4) years. Relapsing remitting MS was the main diagnostic category (n = 123, 67%); 43 (26%) had secondary progressive disease; and the remainder were unspecified. MBIs lasted 6–8 weeks; attrition rates were variable (5-43%); all employed pre- post- measures; two had longer follow up; one at 3, and one at 6 months. Socio-economic status of participants was not made explicit; health service utilisation and costs were not reported. No study reported on perceived stress. All studies reported quality of life (QOL), mental health (anxiety and depression), physical (fatigue, standing balance, pain), and psychosocial measures. Statistically significant beneficial effects relating to QOL, mental health, and selected physical health measures were sustained at 3- and 6- month follow up.<p></p> <b>Conclusion</b> From the limited data available, MBIs may benefit some MS patients in terms of QOL, mental health, and some physical health measures. Further studies are needed to clarify how MBIs might best serve the MS population.<p></p&gt

A review of physical supply and EROI of fossil fuels in China

This paper reviews China’s future fossil fuel supply from the perspectives of physical output and net energy output. Comprehensive analyses of physical output of fossil fuels suggest that China’s total oil production will likely reach its peak, at about 230 Mt/year (or 9.6 EJ/year), in 2018; its total gas production will peak at around 350 Bcm/year (or 13.6 EJ/year) in 2040, while coal production will peak at about 4400 Mt/year (or 91.9 EJ/year) around 2020 or so. In terms of the forecast production of these fuels, there are significant differences among current studies. These differences can be mainly explained by different ultimately recoverable resources assumptions, the nature of the models used, and differences in the historical production data. Due to the future constraints on fossil fuels production, a large gap is projected to grow between domestic supply and demand, which will need to be met by increasing imports. Net energy analyses show that both coal and oil and gas production show a steady declining trend of EROI (energy return on investment) due to the depletion of shallow-buried coal resources and conventional oil and gas resources, which is generally consistent with the approaching peaks of physical production of fossil fuels. The peaks of fossil fuels production, coupled with the decline in EROI ratios, are likely to challenge the sustainable development of Chinese society unless new abundant energy resources with high EROI values can be found

Evidence for nucleotide excision repair as a modifying factor of O6-methylguanine-DNA methyltransferase-mediated innate chloroethylnitrosourea resistance in human tumor cell lines

SUMMARY We examined the O 6 -methylguanine-DNA methyltransferase (MGMT) protein as well as MGMT activity levels and the excision repair cross-complementing rodent repair deficiency gene, ERCC2 (XPD), protein levels in 14 human tumor cell lines not selected for chloroethylnitrosourea (CENU) resistance. These results were compared with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) cytotoxicity and UV light sensitivity. MGMT protein correlated significantly with MGMT activity (r ϭ 0.9497, p ϭ 0.0001). There was no significant linear correlation between BCNU cytotoxicity and MGMT content as determined by both Western analysis (r ϭ 0.139, p ϭ 0.6348) and activity assay (r ϭ 0.131, p ϭ 0.6515). However, MGMT-rich cell lines were found to be more resistant than MGMT-poor cell lines to BCNU (t ϭ 2.2375, p ϭ 0.0225) but not to UV (t ϭ 1.1734, p ϭ 0.1317). Furthermore, the most BCNU-sensitive cell lines were all MGMT-poor. UV sensitivity was significantly correlated to BCNU cytotoxicity (r ϭ 0.858, p ϭ 0.0001). Significant correlations were found between ERCC2 protein levels and BCNU cytotoxicity (r ϭ 0.786, p ϭ 0.0009) or UV sensitivity (r ϭ 0.874, p ϭ 0.0001). Our results confirm that MGMT plays an important role in CENU resistance, but not in UV resistance. The correlation of UV sensitivity with BCNU cytotoxicity suggests that nucleotide excision repair is an important modifying factor of MGMT-mediated innate CENU resistance in human tumor cell lines, especially in highly resistant cell lines. ERCC2 may be implicated in this process

Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

The End of the Rainbow: What Can We Say About the Extragalactic Sub-Megahertz Radio Sky?

The Galactic disc is opaque to radio waves from extragalactic sources with frequencies nu less than ~3 MHz. However, radio waves with kHz, Hz, and even lower frequencies may propagate through the intergalactic medium (IGM). I argue that the presence of these waves can be inferred by using the Universe as our detector. I discuss possible sub-MHz sources and set new non-trivial upper limits on the energy density of sub-MHz radio waves in galaxy clusters and the average cosmic background. Limits based on five effects are considered: (1) changes in the expansion of the Universe from the radiation energy density (2) heating of the IGM by free-free absorption; (3) radiation pressure squeezing of IGM clouds by external radio waves; (4) synchrotron heating of electrons in clusters; and (5) Inverse Compton upscattering of sub-MHz radio photons. Any sub-MHz background must have an energy density much smaller than the CMB at frequencies below 1 MHz. The free-free absorption bounds from the Lyman-alpha forest are potentially the strongest, but are highly dependent on the properties of sub-MHz radio scattering in the IGM. I estimate an upper limit of 6 * 10^4 L_sun Mpc^-3 for the emissivity within Lyman-alpha forest clouds in the frequency range 5 - 200 Hz. The sub-MHz energy density in the Coma cluster is constrained to be less than ~10^-15 erg cm^-3. At present, none of the limits is strong enough to rule out a maximal T_b = 10^12 K sub-MHz synchrotron background, but other sources may be constrained with a better knowledge of sub-MHz radio propagation in the IGM.Comment: Accepted by MNRAS, 4 figures, 20 pages

Distinct contributions of extrastriate body area and temporoparietal junction in perceiving one's own and others' body.

The right temporoparietal cortex plays a critical role in body representation. Here, we applied repetitive transcranial magnetic stimulation (rTMS) over right extrastriate body area (EBA) and temporoparietal junction (TPJ) to investigate their causative roles in perceptual representations of one's own and others' body. Healthy women adjusted size-distorted pictures of their own body or of the body of another person according to how they perceived the body (subjective task) or how others perceived it (intersubjective task). In keeping with previous reports, at baseline, we found an overall underestimation of body size. Crucially, EBA-rTMS increased the underestimation bias when participants adjusted the images according to how others perceived their own or the other woman's body, suggesting a specific role of EBA in allocentric body representations. Conversely, TPJ-rTMS increased the underestimation bias when participants adjusted the body of another person, either a familiar other or a close friend, in both subjective and intersubjective tasks, suggesting an involvement of TPJ in representing others' bodies. These effects were body-specific, since no TMS-induced modulation was observed when participants judged a familiar object. The results suggest that right EBA and TPJ play active and complementary roles in the complex interaction between the perceptions of one's own and other people's body