Pressure Relief Tunnel System at US22/SR7 Interchange, OH

Construction of the US22/SR7 interchange in Steubenville, OH resulted in the need to excavate the toe of the steep 350 ft. high slope overlooking the Ohio River. To maintain the stability of the slope, the Ohio Department of Transportation (ODOT) chose to construct a 4 tier, 130- ft. high, 2,200 ft. long tieback anchor retaining wall. During the design phase, it became apparent that reductions in both the tieback loading and cost could be realized by lowering the groundwater levels in the hillside. A Pressure Relief Tunnel System (PRTS) was selected from several drainage options. The PRTS consists of a 1,945 ft. long tunnel, excavated parallel to, and 200 ft. behind, the retaining wall, and a series 85 ft. long, sub-vertical drainage holes drilled upward from inside the tunnel. This paper presents the design of the PRTS, an outline of the instrumentation program and a comparison of the observed and expected drawdowns

Effects of carnitine and its congeners on eicosanoid discharge from rat cells: implications for release of TNFα

THE acyl carrier coenzyme A (CoA) is involved in fatty acid metabolism. The carnitine/CoA ratio is of particular importance in regulating the transport of long-chain fatty acids into mitochondria for oxidation. Also CoA has a role in the formation and breakdown of products from both the cyclooxygenase and lipoxygenase pathways of the precursor arachidonic acid. In the present study the effect of 4 days feeding of 300 mg/kg/day of L-carnitine, acetyl Lcarnitine and propionyl L-carnitine on the basal and calcium ionophore (A23187) stimulated release of arachidonic acid metabolites from rat carrageenin elicited peritoneal cells was investigated. There were two series of experiments carried out. In the first, the harvested peritoneal cell population consisted of less than 90% macrophages and additional polymorphonuclear (PMN) leucocytes. The basal release of prostaglandin E2 (PGE2), 6-ketoprostaglandin F1α (6-keto-PGF1α) and leukotriene B4 (LTB4) was stimulated by all treatments. The A23187 stimulated release of 6-keto-PGF1α and LTB4 was increased by all three compounds. The 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were increased by carnitine treatment. These results suggested that carnitine could modify the macrophage component of an inflammatory site in vivo. In the second series of experiments the harvested cell population was highly purified (>95% macrophages) and none of the compounds fed to the rats caused a change of either eicosanoid or TNFα formation. Moreover the 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were not enhanced by any of the compounds tested. It is conceivable that in the first series the increased ratios 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 reflected the effect of carnitine or its congeners on PMN leucocytes rather than on macrophages

Predicting sexual problems in women: The relevance of sexual excitation and sexual inhibition

This is the post-print version of the article. The official published version can be obtained from the link below.Data from a non-clinical sample of 540 heterosexual women were used to examine the relationships between scores on the Sexual Excitation/Sexual Inhibition Inventory for Women (SESII-W) and ratings of current sexual problems, lifetime arousal difficulty, lifetime orgasm difficulty, and lifetime problems with low sexual interest. Multiple regression analyses also included several demographic/background variables as predictors: age, full-time employment, completed college, children in household, married, health ratings, importance of sex, and whether the woman was in a sexual relationship. The strongest statistical predictors of both current and lifetime sexual problems were the SESII-W inhibition factors Arousal Contingency and Concerns about Sexual Function. Demographic factors did not feature largely in any of the models predicting sexual problems even when statistically significant relationships were found. If future research supports the predictive utility of the SESII-W in identifying women who are more likely to experience sexual difficulties, these scales may be used as prognostic factors in treatment studies.This study was funded, in part, by a grant from the Lilly Centre for Women's Health

Positive coexistence of water voles and beaver: water vole expansion in a beaver engineered wetland

This is the final version. Available on open access from the Mammal Society via the DOI in this recordWater voles (Arvicola amphibius) are critically endangered in Great Britain and there is a pressing need for successful conservation strategies. Meanwhile, another semi-aquatic rodent, the Eurasian beaver (Castor fiber) is being restored to much of its native range including Great Britain. Beavers are known as ecosystem engineers and keystone species, creating wetland habitats. As part of the River Otter Beaver Trial in South-West England, free-living beavers were reintroduced in a location where water vole were present and being surveyed. Here, we present survey data showing the expansion of water vole into newly beaver engineered wetland areas. We propose that complex beaver wetlands may benefit water vole populations by creating new habitat and providing refuge from predation, warranting further investigation as a nature recovery option

Amplification and Overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in Medulloblastoma

Medulloblastoma is the most common malignant brain tumour of childhood. The identification of critical genes involved in its pathogenesis will be central to advances in our understanding of its molecular basis, and the development of improved therapeutic approaches.We performed a SNP-array based genome-wide copy number analysis in medulloblastoma cell lines, to identify regions of genomic amplification and homozygous deletion, which may harbour critical disease genes. A series of novel and established medulloblastoma defects were detected (MYC amplification (n = 4), 17q21.31 high-level gain (n = 1); 9p21.1-p21.3 (n = 1) and 6q23.1 (n = 1) homozygous deletion). Most notably, a novel recurrent region of genomic amplification at 8q24.22-q24.23 was identified (n = 2), and selected for further investigation. Additional analysis by interphase fluorescence in situ hybridisation (iFISH), PCR-based mapping and SNP-array revealed this novel amplification at 8q24.22-q24.23 is independent of MYC amplification at 8q24.21, and is unique to medulloblastoma in over 800 cancer cell lines assessed from different tumour types, suggesting it contains key genes specifically involved in medulloblastoma development. Detailed mapping identified a 3Mb common minimal region of amplification harbouring 3 coding genes (ZFAT1, LOC286094, KHDRBS3) and two genes encoding micro-RNAs (hsa-miR-30b, hsa-miR-30d). Of these, only expression of hsa-miR-30b, hsa-miR-30d and KHDRBS3 correlated with copy number status, and all three of these transcripts also displayed evidence of elevated expression in sub-sets of primary medulloblastomas, measured relative to the normal cerebellum.These data implicate hsa-miR-30b, hsa-miR-30d and KHDRBS3 as putative oncogenic target(s) of a novel recurrent medulloblastoma amplicon at 8q24.22-q24.23. Our findings suggest critical roles for these genes in medulloblastoma development, and further support the contribution of micro-RNA species to medulloblastoma pathogenesis

‘Just like talking to someone about like shit in your life and stuff, and they help you’: hopes and expectations for therapy among depressed adolescents

Objective: To explore hopes and expectations for therapy among a clinical population of depressed adolescents. Method: As part of a randomised clinical trial, 77 adolescents aged 11 to 17, with moderate to severe depression, were interviewed using a semi-structured interview schedule. The interviews were analysed qualitatively, using Framework Analysis. Results: The findings are reported around five themes: “The difficulty of imagining what will happen in therapy”, "the 'talking cure'"; “the therapist as doctor”, “therapy as a relationship” and “regaining the old self or developing new capacities”. Conclusions: Differing expectations are likely to have implications for the way young people engage with treatment, and failure to identify these expectations may lead to a risk of treatment breakdown

GROND coverage of the main peak of Gamma-Ray Burst 130925A

Prompt or early optical emission in gamma-ray bursts is notoriously difficult to measure, and observations of the dozen cases show a large variety of properties. Yet, such early emission promises to help us achieve a better understanding of the GRB emission process(es). We performed dedicated observations of the ultra-long duration (T90 about 7000 s) GRB 130925A in the optical/near-infrared with the 7-channel "Gamma-Ray Burst Optical and Near-infrared Detector" (GROND) at the 2.2m MPG/ESO telescope. We detect an optical/NIR flare with an amplitude of nearly 2 mag which is delayed with respect to the keV--MeV prompt emission by about 300--400 s. The decay time of this flare is shorter than the duration of the flare (500 s) or its delay. While we cannot offer a straightforward explanation, we discuss the implications of the flare properties and suggest ways toward understanding it.Comment: 9 pages, 9 figures, accepted for publ. in A&

A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus

Summary: The Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies (nAbs) against RVFV Gn, which exhibited protective efficacy in a mouse infection model. Structural characterization revealed that these nAbs were directed to the membrane-distal domain of RVFV Gn and likely prevented virus entry into a host cell by blocking fusogenic rearrangements of the Gn-Gc lattice. Genome sequence analysis confirmed that this region of the RVFV Gn-Gc assembly was under selective pressure and constituted a site of vulnerability on the virion surface. These data provide a blueprint for the rational design of immunotherapeutics and vaccines capable of preventing RVFV infection and a model for understanding Ab-mediated neutralization of bunyaviruses more generally. : Allen et al. reveal a molecular basis of antibody-mediated neutralization of Rift Valley fever virus, an important human and animal pathogen. They isolate and demonstrate the protective efficacy of a monoclonal antibody in a murine model of virus infection, providing a blueprint for rational therapeutic and vaccine design. Keywords: phlebovirus, Rift Valley fever virus, antibody, structure, bunyavirus, virus-host interactions, immune response, vaccine, antiviral, neutralizatio

Regulatory Improvement Legislation: Risk Assessment, Cost-Benefit Analysis, and Judicial Review

As the number, cost, and complexity of federal regulations have grown over the past twenty years, there has been growing interest in the use of analytic tools such as risk assessment and cost-benefit analysis to improve the regulatory process. The application of these tools to public health, safety, and environmental problems has become commonplace in the peer-reviewed scientific and medical literatures. Recent studies prepared by Resources for the Future, the American Enterprise Institute, the Brookings Institution, and the Harvard Center for Risk Analysis have demonstrated how formal analyses can and often do help government agencies achieve more protection against hazards at less cost than would otherwise occur. Although analytic tools hold great promise, their use by federal agencies is neither consistent nor rigorous. The 103rd, 104th, 105th and 106th Congresses demonstrated sustained interest in the passage of comprehensive legislation governing the employment of these tools in the federal regulatory process. While legislative proposals on this issue have attracted significant bipartisan interest, and recent amendments to particular enabling statutes have incorporated some of these analytical requirements, no comprehensive legislation has been enacted into law since passage of the Administrative Procedure Act in 1946. The inability to pass such legislation has been attributed to a variety of factors, but a common substantive concern has been uncertainty and controversy about how such legislation should address judicial review issues. For example, the judicial review portion of The Regulatory Improvement Act (S. 981), the 105th Congress\u27s major legislative initiative, was criticized simultaneously as meaningless (for allegedly offering too few opportunities for petitioners to challenge poorly reasoned agency rules) and dangerous (as supposedly enabling petitioners to paralyze even well-reasoned agency rules). Thus, a significant obstacle to regulatory improvement legislation appears to be the conflicting opinions among legal scholars and practitioners about how judicial review issues should be addressed in such legislation. The Clinton Administration and the authors of S. 981 believe they have crafted a workable compromise, one that accommodates the need to bring more rigor and transparency to an agency\u27s decisional processes without imposing excessive judicial review. Nevertheless, it is clear that their agreement on this subject, if included in future legislative deliberations, will be scrutinized and contested. Recognizing the importance of the judicial review issue to this and, indeed, any effort to improve the regulatory process, the Center for Risk Analysis at the Harvard School of Public Health convened an invitational Workshop of accomplished legal practitioners and scholars to discuss how judicial review should be handled in legislation of this kind. The full-day Workshop was conducted in Washington, D.C. on December 17, 1998. Its purpose was to discuss principles, experiences, and insights that might inform future public debate about how judicial review should be addressed in legislative proposals that entail use of risk assessment and/or cost-benefit analysis in agency decision-making (whether the proposals are comprehensive or agency-specific). In order to provide the Workshop a practical focus, participants analyzed the provisions of S. 981 (as modified at the request of the Clinton Administration). An exchange of letters between S. 981\u27s chief sponsors and the Clinton Administration defining the terms of the agreement was examined as well. This Report highlights the themes of the Workshop discussion and offers some specific commentary on how proposed legislation (including but not limited to S. 981) could be improved in future legislative deliberations