Strategy revision opportunities and collusion

This paper studies whether and how strategy revision opportunities affect levels of collusion in indefinitely repeated two-player games. Consistent with standard theory, we find that such opportunities do not affect strategy choices, or collusion levels, if the game is of strategic substitutes. In games of strategic complements, by contrast, revision opportunities lead to more collusion. We discuss alternative explanations for this result

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras

Strong vacuum squeezing from bichromatically driven Kerrlike cavities: from optomechanics to superconducting circuits

Squeezed light, displaying less fluctuation than vacuum in some observable, is key in the flourishing field of quantum technologies. Optical or microwave cavities containing a Kerr nonlinearity are known to potentially yield large levels of squeezing, which have been recently observed in optomechanics and nonlinear superconducting circuit platforms. Such Kerr-cavity squeezing however suffers from two fundamental drawbacks. First, optimal squeezing requires working close to turning points of a bistable cycle, which are highly unstable against noise thus rendering optimal squeezing inaccessible. Second, the light field has a macroscopic coherent component corresponding to the pump, making it less versatile than the so-called squeezed vacuum, characterised by a null mean field. Here we prove analytically and numerically that the bichromatic pumping of optomechanical and superconducting circuit cavities removes both limitations. This finding should boost the development of a new generation of robust vacuum squeezers in the microwave and optical domains with current technology

An assessment of the malaria-related knowledge and practices of Tanzania's drug retailers: exploring the impact of drug store accreditation.

BACKGROUND: Since 2003 Tanzania has upgraded its approximately 7000 drug stores to Accredited Drug Dispensing Outlets (ADDOs), involving dispenser training, introduction of record keeping and enhanced regulation. Prior to accreditation, drug stores could officially stock over-the-counter medicines only, though many stocked prescription-only antimalarials. ADDOs are permitted to stock 49 prescription-only medicines, including artemisinin combination therapies and one form of quinine injectable. Oral artemisinin monotherapies and other injectables were not permitted at any time. By late 2011 conversion was complete in 14 of 21 regions. We explored variation in malaria-related knowledge and practices of drug retailers in ADDO and non-ADDO regions. METHODS: Data were collected as part of the Independent Evaluation of the Affordable Medicines Facility - malaria (AMFm), involving a nationally representative survey of antimalarial retailers in October-December 2011. We randomly selected 49 wards and interviewed all drug stores stocking antimalarials. We compare ADDO and non-ADDO regions, excluding the largest city, Dar es Salaam, due to the unique characteristics of its market. RESULTS: Interviews were conducted in 133 drug stores in ADDO regions and 119 in non-ADDO regions. Staff qualifications were very similar in both areas. There was no significant difference in the availability of the first line antimalarial (68.9% in ADDO regions and 65.2% in non-ADDO regions); both areas had over 98% availability of non-artemisinin therapies and below 3.0% of artemisinin monotherapies. Staff in ADDO regions had better knowledge of the first line antimalarial than non-ADDO regions (99.5% and 91.5%, p = 0.001). There was weak evidence of a lower price and higher market share of the first line antimalarial in ADDO regions. Drug stores in ADDO regions were more likely to stock ADDO-certified injectables than those in non-ADDO regions (23.0% and 3.9%, p = 0.005). CONCLUSIONS: ADDO conversion is frequently cited as a model for improving retail sector drug provision. Drug stores in ADDO regions performed better on some indicators, possibly indicating some small benefits from ADDO conversion, but also weaknesses in ADDO regulation and high staff turnover. More evidence is needed on the value-added and value for money of the ADDO roll out to inform retail policy in Tanzania and elsewhere

How HIV/AIDS scale-up has impacted on non- HIV priority services in Zambia

Background: Much of the debate as to whether or not the scaling up of HIV service delivery in Africa benefits non-HIV priority services has focused on the use of nationally aggregated data. This paper analyses and presents routine health facility record data to show trend correlations across priority services. Methods: Review of district office and health facility client records for 39 health facilities in three districts of Zambia, covering four consecutive years (2004-07). Intra-facility analyses were conducted, service and coverage trends assessed and rank correlations between services measured to compare service trends within facilities. Results: VCT, ART and PMTCT client numbers and coverage levels increased rapidly. There were some strong positive correlations in trends within facilities between reproductive health services (family planning and antenatal care) and ART and PMTCT, with Spearman rank correlations ranging from 0.33 to 0.83. Childhood immunisation coverage also increased. Stock-outs of important drugs for non-HIV priority services were significantly more frequent than were stock-outs of antiretroviral drugs. Conclusions: The analysis shows scale-up in reproductive health service numbers in the same facilities where HIV services were scaling up. While district childhood immunisations increased overall, this did not necessarily occur in facility catchment areas where HIV service scale-up occurred. The paper demonstrates an approach for comparing correlation trends across different services, using routine health facility information. Larger samples and explanatory studies are needed to understand the client, facility and health systems factors that contribute to positive and negative synergies between priority services

Primary sensory and motor cortex excitability are co-modulated in response to peripheral electrical nerve stimulation

Peripheral electrical stimulation (PES) is a common clinical technique known to induce changes in corticomotor excitability; PES applied to induce a tetanic motor contraction increases, and PES at sub-motor threshold (sensory) intensities decreases, corticomotor excitability. Understanding of the mechanisms underlying these opposite changes in corticomotor excitability remains elusive. Modulation of primary sensory cortex (S1) excitability could underlie altered corticomotor excitability with PES. Here we examined whether changes in primary sensory (S1) and motor (M1) cortex excitability follow the same timecourse when PES is applied using identical stimulus parameters. Corticomotor excitability was measured using transcranial magnetic stimulation (TMS) and sensory cortex excitability using somatosensory evoked potentials (SEPs) before and after 30 min of PES to right abductor pollicis brevis (APB). Two PES paradigms were tested in separate sessions; PES sufficient to induce a tetanic motor contraction (30–50 Hz; strong motor intensity) and PES at sub motor-threshold intensity (100 Hz). PES applied to induce strong activation of APB increased the size of the N20-P25 component, thought to reflect sensory processing at cortical level, and increased corticomotor excitability. PES at sensory intensity decreased the size of the P25-N33 component and reduced corticomotor excitability. A positive correlation was observed between the changes in amplitude of the cortical SEP components and corticomotor excitability following sensory and motor PES. Sensory PES also increased the sub-cortical P14-N20 SEP component. These findings provide evidence that PES results in co-modulation of S1 and M1 excitability, possibly due to cortico-cortical projections between S1 and M1. This mechanism may underpin changes in corticomotor excitability in response to afferent input generated by PES.Siobhan M. Schabrun, Michael C. Ridding, Mary P. Galea, Paul W. Hodges and Lucinda S. Chipchas