Synthetic Studies on Gibberellins

Based upon the serendipitous conversion of carbomethoxy-2-(p-methoxyphenyl)-cyclohexane-1-carboxylic acid into endo-2-(p-methoxyphenyl)-cyclohexane-cis-1,5-dicarboxylic acid anhydride, a stereospecific synthesis of 1,2,3,4,4a(betaH),9a(betaH)-hexahydro-7-methoxy-o-oxofluorene-2-carboxylic acid has been achieved in excellent yield, originating from the regiospecific and stereoselective Diels Alder cyclisation between acrylyl chloride and 5-(p-methoxyphenyl)-trans, trans-penta-2,4-dienoyl chloride. The Diels Alder reaction between related dienes and dienophiles was also investigated. A detailed investigation of the intramolecular Dieckmann cyclisation of methyl (1,2,3,4,4a(betaH),9a-hexahydro-2-carbomethoxy-7-methoxy-9-oxofluorenyl-9abeta)-acetate and of its 9-desoxy and 9alpha-hydroxy derivatives as a route to 3-methoxy-6,16-dioxo-9(betaH)-gibb-A-triene suggests that strain factors are the cause of failure of this cyclisation. 3-methoxy-16-oxogibba-1(10),2,4 ,9(11)-tetraene was obtained by acid catalysed cyclisation of the olefinic diazo ketone, 1,2,3,4,4a(betaH)-tetrahydro-Delta9,11-2-diazoacyl-7-methoxyfluorene. A keto-carbenoid C-H insertion reaction applied to the corresponding hexahydro and 9alpha-hydroxy-hexahydro derivatives failed to yield any tetracyclic material. An attempt to extend the Parham hydrofluorene synthesis failed at an early stage when 2-bromo-5-methoxybenzyl alcohol, or its 1-alkoxy-l-ethoxyethane acetal derivative failed to undergo electrophilic halogen exchange. A similar lack of success was experienced with the corresponding Grignard reagent

How 'dynasty' became a modern global concept : intellectual histories of sovereignty and property

The modern concept of ‘dynasty’ is a politically-motivated modern intellectual invention. For many advocates of a strong sovereign nation-state across the nineteenth and early twentieth century, in France, Germany, and Japan, the concept helped in visualizing the nation-state as a primordial entity sealed by the continuity of birth and blood, indeed by the perpetuity of sovereignty. Hegel’s references to ‘dynasty’, read with Marx’s critique, further show how ‘dynasty’ encoded the intersection of sovereignty and big property, indeed the coming into self-consciousness of their mutual identification-in-difference in the age of capitalism. Imaginaries about ‘dynasty’ also connected national sovereignty with patriarchal authority. European colonialism helped globalize the concept in the non-European world; British India offers an exemplar of ensuing debates. The globalization of the abstraction of ‘dynasty’ was ultimately bound to the globalization of capitalist-colonial infrastructures of production, circulation, violence, and exploitation. Simultaneously, colonized actors, like Indian peasant/‘tribal’ populations, brought to play alternate precolonial Indian-origin concepts of collective regality, expressed through terms like ‘rajavamshi’ and ‘Kshatriya’. These concepts nourished new forms of democracy in modern India. Global intellectual histories can thus expand political thought today by provincializing and deconstructing Eurocentric political vocabularies and by recuperating subaltern models of collective and polyarchic power.PostprintPeer reviewe

Neuroimaging in encephalitis:analysis of imaging findings and interobserver agreement

AimTo assess the role of imaging in the early management of encephalitis and the agreement on findings in a well-defined cohort of suspected encephalitis cases enrolled in the Prospective Aetiological Study of Encephalitis conducted by the Health Protection Agency (now incorporated into Public Health England).Materials and methodsEighty-five CT examinations from 68 patients and 101 MRI examinations from 80 patients with suspected encephalitis were independently rated by three neuroradiologists blinded to patient and clinical details. The level of agreement on the interpretation of images was measured using the kappa statistic. The sensitivity, specificity, and negative and positive predictive values of CT and MRI for herpes simplex virus (HSV) encephalitis and acute disseminated encephalomyelitis (ADEM) were estimated.ResultsThe kappa value for interobserver agreement on rating the scans as normal or abnormal was good (0.65) for CT and moderate (0.59) for MRI. Agreement for HSV encephalitis was very good for CT (0.87) and MRI (0.82), but only fair for ADEM (0.32 CT; 0.31 MRI). Similarly, the overall sensitivity of imaging for HSV encephalitis was ∼80% for both CT and MRI, whereas for ADEM it was 0% for CT and 20% for MRI. MRI specificity for HSV encephalitis between 3–10 days after symptom onset was 100%.ConclusionThere is a subjective component to scan interpretation that can have important implications for the clinical management of encephalitis cases. Neuroradiologists were good at diagnosing HSV encephalitis; however, agreement was worse for ADEM and other alternative aetiologies. Findings highlight the importance of a comprehensive and multidisciplinary approach to diagnosing the cause of encephalitis that takes into account individual clinical, microbiological, and radiological features of each patient

Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program.

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children's health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO's rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children