Pharmaco-economic assessment of the HMGCoA reductase inhibitors

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A ‘criminal personas’ approach to countering criminal creativity

This paper describes a pilot study of a ‘criminal personas’ approach to countering criminal creativity. The value of the personas approach has been assessed by comparing the identification of criminal opportunity, through ‘traditional’ brainstorming and then through ‘criminal personas’ brainstorming The method involved brainstorm sessions with Computer Forensics Practitioners and with Product Designers, where they were required to generate criminal scenarios, select the most serious criminal opportunities, and propose means of countering them. The findings indicated that there was merit in further research in the development and application of the ‘criminal personas’ approach. The generation of criminal opportunity ideas and proposal of counter criminal solutions were both greater when the brainstorm approach involved the group responding through their given criminal personas

Financial contagion in large, inhomogeneous stochastic interbank networks

We consider the fraction of nodes that default in large, stochastic, inhomogeneous financial networks following an initial shock to the system. Results for deterministic sequences of networks are generalized to stochastic networks to account for interbank lending relationships that change frequently. A general class of inhomogeneous stochastic networks is proposed for use in systemic risk research, and we illustrate how results that hold for Erdős–Rényi networks can be generalized to the proposed network class. The network structure of a system is determined by interbank lending behavior which may vary according to the relative sizes of the banks. We then use the results of the paper to illustrate how network structure influences the systemic risk inherent in large banking systems.The National Research Foundation (NRF) and the ABSA chair in Actuarial Science.https://www.worldscientific.com/worldscinet/acs2020-03-04hj2019Insurance and Actuarial ScienceMathematics and Applied Mathematic

Dysfunctional Dopaminergic Neurones in Mouse Models of Huntington's Disease: A Role for SK3 Channels

Background: Huntington's disease (HD) is a late-onset fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene coding for the protein huntingtin and is characterised by progressive motor, psychiatric and cognitive decline. We previously demonstrated that normal synaptic function in HD could be restored by application of dopamine receptor agonists, suggesting that changes in the release or bioavailability of dopamine may be a contributing factor to the disease process. Objective: In the present study, we examined the properties of midbrain dopaminergic neurones and dopamine release in presymptomatic and symptomatic transgenic HD mice. Methods and Results:Using intracellular sharp recordings and immunohistochemistry, we found that neuronal excitability was increased due to a loss of slow afterhyperpolarisation and that these changes were related to an apparent functional loss and abnormal distribution of SK3 channels (KCa2.3 encoded by the KCNN3 gene), a class of small-conductance calcium-activated potassium channels. Electrochemical detection of dopamine showed that this observation was associated with an enhanced dopamine release in presymptomatic transgenic mice and a drastic reduction in symptomatic animals. These changes occurred in the context of a progressive expansion in the CAG repeat number and nuclear localisation of mutant protein within the substantia nigra pars compacta. Conclusions: Dopaminergic neuronal dysfunction is a key early event in HD disease progression. The initial increase in dopamine release appears to be related to a loss of SK3 channel function, a protein containing a polyglutamine tract. Implications for polyglutamine-mediated sequestration of SK3 channels, dopamine-associated DNA damage and CAG expansion are discussed in the context of HD.</br

Large rivers and orogens: the evolution of the Yarlung Tsangpo–Irrawaddy system and the eastern Himalayan syntaxis

The eastern Himalayan syntaxis has experienced some of the highest rates of deformation and erosion in the orogen during the Late Cenozoic, and the Yarlung Tsangpo, Brahmaputra, Irrawaddy, Salween, and Mekong rivers are the key erosional systems in that region. The Yarlung Tsangpo drains southern Tibet and the deep Siang River gorge through the eastern Himalayan syntaxis before joining the Brahmaputra in northeastern India. It has been proposed that the Yarlung Tsangpo drained into other large rivers of southern Asia, such as the Irrawaddy, Salween and Red River. We have used uranium/lead dating and hafnium measurements of detrital zircons from Cenozoic sedimentary deposits in Central Myanmar to demonstrate that the Yarlung Tsangpo formerly drained into the Irrawaddy River in Myanmar through the eastern syntaxis, and that this ancient river system was established by (at least) the Middle–Late Eocene. The Yarlung Tsangpo–Irrawaddy river disconnected in the Early Miocene driven by increased deformation in the eastern syntaxis and headward erosion by tributaries of the Brahmaputra. Our results highlight the significance of the sedimentary record of large orogen-parallel rivers and provide key chronological constraints on landscape evolution during the Early Miocene phase of the Himalayan orogeny

A framework for simulating systemic risk and its application to the South African banking sector

We present a network-based framework for simulating systemic risk that considers shock propagation in banking systems. In particular, the framework allows the modeller to reflect a top-down framework where a shock to one bank in the system affects the solvency and liquidity position of other banks, through systemic market risks and consequential liquidity strains. We illustrate the framework with an application using South African bank balance sheet data. Spikes in simulated assessments of systemic risk agree closely with spikes in documented subjective assessments of this risk. This indicates that network models can be useful for monitoring systemic risk levels. The model results are sensitive to liquidity risk and market sentiment and therefore the related parameters are important considerations when using a network approach to systemic risk modelling.The National Research Foundation (NRF) and the Absa chair in Actuarial Science.https://www.actuarialsociety.org.za/assa-news/sa-actuarial-journal-and-articlesam2019Mathematics and Applied Mathematic

The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Background: Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases. Methods: We combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases. Results: PRS for both population IQ (P = 4.39 × 10–28) and EA (P = 1.27 × 10–26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS. Conclusions: Cognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that pr

The position of graptolites within Lower Palaeozoic planktic ecosystems.

An integrated approach has been used to assess the palaeoecology of graptolites both as a discrete group and also as a part of the biota present within Ordovician and Silurian planktic realms. Study of the functional morphology of graptolites and comparisons with recent ecological analogues demonstrates that graptolites most probably filled a variety of niches as primary consumers, with modes of life related to the colony morphotype. Graptolite coloniality was extremely ordered, lacking any close morphological analogues in Recent faunas. To obtain maximum functional efficiency, graptolites would have needed varying degrees of coordinated automobility. A change in lifestyle related to ontogenetic changes was prevalent within many graptolite groups. Differing lifestyle was reflected by differing reproductive strategies, with synrhabdosomes most likely being a method for rapid asexual reproduction. Direct evidence in the form of graptolithophage 'coprolitic' bodies, as well as indirect evidence in the form of probable defensive adaptations, indicate that graptolites comprised a food item for a variety of predators. Graptolites were also hosts to a variety of parasitic organisms and provided an important nutrient source for scavenging organisms

Seasonal size variation in the predatory cladoceran Bythotrephes cederstroemii in Lake Michigan

1.  Dry weight, body length and spine length were measured for the exotic cladoceran Bythotrephes cederstroemii collected from offshore and inshore stations in southeastern Lake Michigan. Average dry weight of each developmental stage exhibited seasonal variation by a factor of more than 5. 2.  Mean dry weight of Bythotrephes was closely correlated with water temperature. Contrary to the inverse relationship between water temperature and body size frequently observed for other invertebrates, the dry weight of Bythotrephes increased at higher ambient temperatures. 3.  No significant correlation was observed between abundances of major zooplankton taxa and the dry weight of Bythotrephes . An indirect effect of temperature on prey consumption may cause seasonal variation in dry weight of Bythotrephes in Lake Michigan. 4.  Distances between adjacent pairs of barbs, added to the caudal spine with each moult, are significantly shorter in Bythotrephes which produce resting eggs. Less material investment in the exoskeleton of sexually reproducing females was observed in favour of growth and reproduction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74641/1/j.1365-2427.1994.tb00842.x.pd

Nucleon Decay Searches with large Liquid Argon TPC Detectors at Shallow Depths: atmospheric neutrinos and cosmogenic backgrounds

Grand Unification of the strong, weak and electromagnetic interactions into a single unified gauge group is an extremely appealing idea which has been vigorously pursued theoretically and experimentally for many years. The detection of proton or bound-neutron decays would represent its most direct experimental evidence. In this context, we studied the physics potentialities of very large underground Liquid Argon Time Projection Chambers (LAr TPC). We carried out a detailed simulation of signal efficiency and background sources, including atmospheric neutrinos and cosmogenic backgrounds. We point out that a liquid Argon TPC, offering good granularity and energy resolution, low particle detection threshold, and excellent background discrimination, should yield very good signal over background ratios in many possible decay modes, allowing to reach partial lifetime sensitivities in the range of 1034−1035 years with exposures up to 1000 kton×year, often in quasi-background-free conditions optimal for discoveries at the few events level, corresponding to atmospheric neutrino background rejections of the order of 105. Multi-prong decay modes like e.g. p→μ−π+K+ or p→e+π+π− and channels involving kaons like e.g. p→K+ν¯, p→e+K0 and p→μ+K0 are particularly suitable, since liquid Argon imaging (...)This work was in part supported by ETH and the Swiss National Foundation. AB, AJM and SN have been supported by CICYT Grants FPA-2002-01835 and FPA-2005-07605-C02-01. SN acknowledges support from the Ramon y Cajal Programme. We thank P. Sala for help with FLUKA while she was an ETH employee