623 research outputs found

    Topological Hochschild homology and the Bass trace conjecture

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    Abstract. We use the methods of topological Hochschild homology to shed new light on groups satisfying the Bass trace conjecture. Factorization of the Hattori-Stallings rank map through the Bökstedt-Hsiang-Madsen cyclotomic trace map leads to Linnell's restriction on such groups. As a new consequence of this restriction, we show that the conjecture holds for any group G wherein every subgroup isomorphic to the additive group of rational numbers has nontrivial and central image in some quotient of G

    Shriver National Institute of Child Health and Human Development

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    ABSTRACT N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamatergic receptors that have been implicated in learning, development, and neuropathological conditions. They are typically composed of GluN1 and GluN2A-D subunits. Whereas a great deal is known about the role of GluN2A-and GluN2B-containing NMDARs, much less is known about GluN2D-containing NMDARs. Here we explore the subunit composition of synaptic NMDARs on hippocampal interneurons. GluN2D mRNA was detected by single-cell PCR and in situ hybridization in diverse interneuron subtypes in the CA1 region of the hippocampus. The GluN2D subunit was detectable by immunoblotting and immunohistochemistry in all subfields of the hippocampus in young and adult mice. In whole-cell patch-clamp recordings from acute hippocampal slices, (1)-CIQ, the active enantiomer of the positive allosteric modulator CIQ, significantly enhanced the amplitude of the NMDAR component of miniature excitatory postsynaptic currents (mEPSCs) in CA1 interneurons but not in pyramidal cells. (1)-CIQ had no effect in slices from Grin2d2/2 mice, suggesting that GluN2D-containing NMDARs participate in excitatory synaptic transmission onto hippocampal interneurons. The time course of the NMDAR component of the mEPSC was unaffected by (1)-CIQ potentiation and was not accelerated in slices from Grin2d2/2 mice compared with wild-type, suggesting that GluN2D does not detectably slow the NMDAR EPSC time course at this age. (1)-CIQ increased the activity of CA1 interneurons as detected by the rate and net charge transfer of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from CA1 pyramidal cells. These data provide evidence that interneurons contain synaptic NMDARs possessing a GluN2D subunit, which can influence interneuron function and signal processing

    Malaysia and the end of the Bretton Woods system 1965-72: disentangling from Sterling

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    This article examines the tense and complex monetary relationship between Britain, Singapore and Malaysia in the period from 1965 to 1972. It questions the assumption that Malaysia's economic significance to Britain was 'on the wane' by the 1960s. As the second largest government holder of sterling assets in the world, Malaysia should have been able to exert considerable leverage in London over the disposition of these assets. Ultimately, however, the very scale of these assets limited Malaysia's room for manoeuvre, as it could not sell off a significant proportion of them without undermining international confidence in the exchange rate of the pound and thereby precipitating the devaluation of its remaining sterling assets. The devaluation of sterling in 1967 emerges as a watershed in relations between London and Kuala Lumpur, with the Malaysians thereafter seeking to forge a more independent monetary policy. It is clear, however, that they did not actually succeed in doing so until 1972

    Societal Costs and Benefits of Treatment with Trastuzumab in Patients with Early HER2neu-Overexpressing Breast Cancer in Singapore

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    <p>Abstract</p> <p>Background</p> <p>Trastuzumab has revolutionized the way we treat early Her2Neu-positive breast cancer, as it significantly improves disease-free and overall survival. Little is known about the societal costs and benefits of treatment with trastuzumab in the adjuvant setting in Southeast Asia.</p> <p>Methods</p> <p>Societal costs (benefits) were estimated as the sum of direct and indirect costs minus benefits in the base case. Direct costs were derived from 4 treatment centers in Singapore (2 private and 2 public, comprising 60-70% of all patients with cancer seen in the island-nation); indirect costs were assessed as the loss of productivity caused by the disease or treatment. Benefits to society were based on extra years of productivity, as measured by GNI per capita, resulting from the quality adjusted life-years (QALYs) saved with the use of trastuzumab as determined in the models by Kurian, Liberato and Garrison.</p> <p>Results</p> <p>Incremental costs in Singapore, in 2005 US dollars, were 26,971.05.AverageCostperQALYwas26,971.05. Average Cost per QALY was 19,174.59 (Median: 18,993.70).Costs(benefits)tosocietyrangedfromacostof18,993.70). Costs (benefits) to society ranged from a cost of 79.42 to a benefit of 9,263.06,dependingonthemodelused(Averagebenefit:9,263.06, depending on the model used (Average benefit: 4,375.89, Median 3,944.03).Sensitivityanalysisrangedfromacostof3,944.03). Sensitivity analysis ranged from a cost of 10,685.00 to a Benefit of US$17,298.79</p> <p>Conclusions</p> <p>Treatment with adjuvant trastuzumab is likely to generate net societal economic benefits in Singapore. Nevertheless, the lower range of possible outcomes does not refute the possibility that treatment may actually generate costs. These costs however clearly fall within the usual range of acceptable cost-effectiveness.</p

    Dominion cartoon satire as trench culture narratives: complaints, endurance and stoicism

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    Although Dominion soldiers’ Great War field publications are relatively well known, the way troops created cartoon multi-panel formats in some of them has been neglected as a record of satirical social observation. Visual narrative humour provides a ‘bottom-up’ perspective for journalistic observations that in many cases capture the spirit of the army in terms of stoicism, buoyed by a culture of internal complaints. Troop concerns expressed in the early comic strips of Australians, Canadians, New Zealanders and British were similar. They shared a collective editorial purpose of morale boosting among the ranks through the use of everyday narratives that elevated the anti-heroism of the citizen soldier, portrayed as a transnational everyman in the service of empire. The regenerative value of disparagement humour provided a redefinition of courage as the very act of endurance on the Western Front

    Seroconversion and asymptomatic infections during oseltamivir prophylaxis against Influenza A H1N1 2009

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    <p>Abstract</p> <p>Background</p> <p>Anti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxis and after cessation of prophylaxis.</p> <p>Methods</p> <p>Between 22 Jun and 16 Jul 09, we performed a cohort study in 3 outbreaks in the Singapore military where post-exposure oseltamivir ring chemoprophylaxis (75 mg daily for 10 days) was administered. The entire cohort was screened by RT-PCR (with HA gene primers) using nasopharyngeal swabs three times a week. Three blood samples were taken for haemagglutination inhibition testing - at the start of outbreak, 2 weeks after completion of 10 day oseltamivir prophylaxis, and 3 weeks after the pandemic's peak in Singapore. Questionnaires were also administered to collect clinical symptoms.</p> <p>Results</p> <p>237 personnel were included for analysis. The overall infection rate of 2009 Influenza A (H1N1) during the three outbreaks was 11.4% (27/237). This included 11 index cases and 16 personnel (7.1%) who developed four-fold or higher rise in antibody titres during oseltamivir prophylaxis. Of these 16 personnel, 8 (3.5%) were symptomatic while the remaining 8 personnel (3.5%) were asymptomatic and tested negative on PCR. Post-cessation of prophylaxis, an additional 23 (12.1%) seroconverted. There was no significant difference in mean fold-rise in GMT between those who seroconverted during and post-prophylaxis (11.3 vs 11.7, p = 0.888). No allergic, neuropsychiatric or other severe side-effects were noted.</p> <p>Conclusions</p> <p>Post-exposure oseltamivir prophylaxis reduced the rate of infection during outbreaks, and did not substantially increase subsequent infection rates upon cessation. Asymptomatic infections occur during prophylaxis, which may confer protection against future infection. Post-exposure prophylaxis is effective as a measure in mitigating pandemic influenza outbreaks.</p

    Shared decision making in breast cancer treatment guidelines: Development of a quality assessment tool and a systematic review

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    Background: It is not clear whether clinical practice guidelines (CPGs) and consensus statements (CSs) are adequately promoting shared decision making (SDM). Objective: To evaluate the recommendations about SDM in CPGs and CSs concerning breast cancer (BC) treatment. Search strategy: Following protocol registration (Prospero no.: CRD42018106643), CPGs and CSs on BC treatment were identified, without language restrictions, through systematic search of bibliographic databases (MEDLINE, EMBASE, Web of Science, Scopus, CDSR) and online sources (12 guideline databases and 51 professional society websites) from January 2010 to December 2019. Inclusion criteria: CPGs and CSs on BC treatment were selected whether published in a journal or in an online document. Data extraction and synthesis: A 31-item SDM quality assessment tool was developed and used to extract data in duplicate. Main results: There were 167 relevant CPGs (139) and CSs (28); SDM was reported in only 40% of the studies. SDM was reported more often in recent publications after 2015 (42/101 (41.6 %) vs 46/66 (69.7 %), P = .0003) but less often in medical journal publications (44/101 (43.5 %) vs 17/66 (25.7 %), P = .009). In CPGs and CSs with SDM, only 8/66 (12%) met one-fifth (6 of 31) of the quality items; only 14/66 (8%) provided clear and precise SDM recommendations. Discussion and conclusions: SDM descriptions and recommendations in CPGs and CSs concerning BC treatment need improvement. SDM was more frequently reported in CPGs and CSs in recent years, but surprisingly it was less often covered in medical journals, a feature that needs attention
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