Circles, columns and screenings: mapping the institutional, discursive, physical and gendered spaces of film criticism in 1940s London

This article revisits the period considered within ‘The Quality Film Adventure: British Critics and the Cinema 1942-1948’, mapping the professional cultures, working contexts and industry relationships that underpinned the aesthetic judgements and collective directions which John Ellis has observed within the critics published writings. Drawing on the records of the Critics’ Circle, Dilys Powell’s papers and Kinematograph Weekly, it explores the evolution of increasingly organised professional cultures of film criticism and film publicity, arguing that the material conditions imposed by war caused tensions between them to escalate. In the context of two major challenges to critical integrity and practice – the evidence given by British producer R.J. Minney in front of the 1948 Royal Commission on the Press and an ongoing libel case between a BBC critic and MGM – the different spaces of hospitality and film promotion became highly contested sites. This article focuses on the ways in which these spaces were characterised, used, and policed. It finds that the value and purpose of press screenings were hotly disputed and observes the way the advancement of women within one sector (film criticism) but not the other (film publicity) created particular difficulties, as key female critics avoided the more compromised masculine spaces of publicity, making them harder for publicists to reach and fuelling trade resentment. More broadly, the article asserts the need to consider film critics as geographically and culturally located audiences, who experience films as ‘professional’ viewers within extended and embodied cultures of habitual professional practice and physical space

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

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

Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy

BackgroundThere are no definitive markers to aid in diagnosis of neonatal encephalopathy (NE). The purpose of our study was (1) to identify and evaluate the utility of neuronal nitric oxide synthase (NOS1) in umbilical cord blood as a NE biomarker and (2) to identify the source of NOS1 in umbilical cord blood.MethodsThis was a nested case–control study of neonates >35 weeks of gestation. ELISA for NOS1 in umbilical cord blood was performed. Sources of NOS1 in umbilical cord were investigated by immunohistochemistry, western blot, ELISA, and quantitative PCR. Furthermore, umbilical cords of full-term neonates were subjected to 1% hypoxia ex vivo.ResultsNOS1 was present in umbilical cord blood and increased in NE cases compared with controls. NOS1 was expressed in endothelial cells of the umbilical cord vein, but not in artery or blood cells. In ex vivo experiments, hypoxia was associated with increased levels of NOS1 in venous endothelial cells of the umbilical cord as well as in ex vivo culture medium.ConclusionThis is the first study to investigate an early marker of NE. NOS1 is elevated with hypoxia, and further studies are needed to investigate it as a valuable tool for early diagnosis of neonatal brain injury

Germline variants are associated with increased primary melanoma tumor thickness at diagnosis

Germline genetic variants have been identified, which predispose individuals and families to develop melanoma. Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness. To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness. The analyses utilized 10 604 individuals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated individuals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 individuals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry. We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P < 5 × 10-8) with tumor thickness. Our work indicates that sufficiently large datasets will enable the discovery of genetic variants associated with greater tumor thickness, and this will lead to the identification of host biological processes influencing melanoma growth and invasion.E.M. was supported by the Malaysian Ministry of Higher Education and Universiti Sains Malaysia to study for a PhD at the University of Leeds. A.E.C. was supported by a National Health and Medical Research Council (NHMRC) of Australia Career Development Fellowship (1147843). K.K. was supported by an NHMRC Career Development Fellowship (1125290). M.M.I. was supported by Cancer Research UK (c588/a19167) and the NIH (ca083115). R.A.S. and G.V.L. are supported by NHMRC Practitioner Fellowships; R.A.S. and J.F.T. also acknowledge support from an NHMRC program grant. D.C.W., S.M. and N.K.H were supported by NHMRC Research Fellowships (1058522, 1155413, 1154543 and 1117663). We thank Nicholas G. Martin for assistance with access to data from the Q-MEGA cohort and with manuscript writing. This work was conducted using the UK Biobank Resource (application number 25331)

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Saying and believing: the norm commonality assumption

One very popular assumption in the epistemological literature is that belief and assertion are governed by one and the same epistemic norm. This paper challenges this claim. Extant arguments in defence of the view are scrutinized and found to rest on value-theoretic inaccuracies. First, the belief-assertion parallel is shown to lack the needed normative strength. Second, I argue that the claim that assertion inherits the norm of belief in virtue of being an expression thereof rests on a failed instance of deontic transmission. Third, the inheritance argument from the norm for action is proven guilty of deontic equivocation. Last but not least, it is argued that, on a functionalist normative picture, assertion and belief are governed by different epistemic norms, in virtue of serving different epistemic functions

Spontaneous Abortion and Preterm Labor and Delivery in Nonhuman Primates: Evidence from a Captive Colony of Chimpanzees (Pan troglodytes)

Preterm birth is a leading cause of perinatal mortality, yet the evolutionary history of this obstetrical syndrome is largely unknown in nonhuman primate species.We examined the length of gestation during pregnancies that occurred in a captive chimpanzee colony by inspecting veterinary and behavioral records spanning a total of thirty years. Upon examination of these records we were able to confidently estimate gestation length for 93 of the 97 (96%) pregnancies recorded at the colony. In total, 78 singleton gestations resulted in live birth, and from these pregnancies we estimated the mean gestation length of normal chimpanzee pregnancies to be 228 days, a finding consistent with other published reports. We also calculated that the range of gestation in normal chimpanzee pregnancies is approximately forty days. Of the remaining fifteen pregnancies, only one of the offspring survived, suggesting viability for chimpanzees requires a gestation of approximately 200 days. These fifteen pregnancies constitute spontaneous abortions and preterm deliveries, for which the upper gestational age limit was defined as 2 SD from the mean length of gestation (208 days).The present study documents that preterm birth occurred within our study population of captive chimpanzees. As in humans, pregnancy loss is not uncommon in chimpanzees, In addition, our findings indicate that both humans and chimpanzees show a similar range of normal variation in gestation length, suggesting this was the case at the time of their last common ancestor (LCA). Nevertheless, our data suggest that whereas chimpanzees' normal gestation length is ∼20-30 days after reaching viability, humans' normal gestation length is approximately 50 days beyond the estimated date of viability without medical intervention. Future research using a comparative evolutionary framework should help to clarify the extent to which mechanisms at work in normal and preterm parturition are shared in these species

Global human footprint on the linkage between biodiversity and ecosystem functioning in reef fishes

Copyright: © 2011 Mora et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Difficulties in scaling up theoretical and experimental results have raised controversy over the consequences of biodiversity loss for the functioning of natural ecosystems. Using a global survey of reef fish assemblages, we show that in contrast to previous theoretical and experimental studies, ecosystem functioning (as measured by standing biomass) scales in a non-saturating manner with biodiversity (as measured by species and functional richness) in this ecosystem. Our field study also shows a significant and negative interaction between human population density and biodiversity on ecosystem functioning (i.e., for the same human density there were larger reductions in standing biomass at more diverse reefs). Human effects were found to be related to fishing, coastal development, and land use stressors, and currently affect over 75% of the world's coral reefs. Our results indicate that the consequences of biodiversity loss in coral reefs have been considerably underestimated based on existing knowledge and that reef fish assemblages, particularly the most diverse, are greatly vulnerable to the expansion and intensity of anthropogenic stressors in coastal areas

Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium

Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the retinal microcirculation and that both channel expression and activity is downregulated by hyperglycaemia. Quantitative PCR and immunostaining demonstrated molecular expression of TRPV4 in cultured bovine retinal microvascular endothelial cells (RMECs). Functional TRPV4 activity was assessed in cultured RMECs from endothelial Ca2+-responses recorded using fura-2 microfluorimetry and electrophysiological recordings of membrane currents. The TRPV4 agonist 4α-phorbol 12,13-didecanoate (4-αPDD) increased [Ca2+]i in RMECs and this response was largely abolished using siRNA targeted against TRPV4. These Ca2+-signals were completely inhibited by removal of extracellular Ca2+, confirming their dependence on influx of extracellular Ca2+. The 4-αPDD Ca2+-response recorded in the presence of cyclopiazonic acid (CPA), which depletes the intracellular stores preventing any signal amplification through store release, was used as a measure of Ca2+-influx across the cell membrane. This response was blocked by HC067047, a TRPV4 antagonist. Under voltage clamp conditions, the TRPV4 agonist GSK1016790A stimulated a membrane current, which was again inhibited by HC067047. Following incubation with 25 mM D-glucose TRPV4 expression was reduced in comparison with RMECs cultured under control conditions, as were 4αPDD-induced Ca2+-responses in the presence of CPA and ion currents evoked by GSK1016790A. Molecular expression of TRPV4 in the retinal vascular endothelium of 3 months' streptozotocin-induced diabetic rats was also reduced in comparison with that in age-matched controls. We conclude that hyperglycaemia and diabetes reduce the molecular and functional expression of TRPV4 channels in retinal microvascular endothelial cells. These changes may contribute to diabetes induced endothelial dysfunction and retinopathy