Prevalence of HCV NS3 pre-treatment resistance associated amino acid variants within a Scottish cohort

Background: Protease inhibitors (PI) including boceprevir, telaprevir and simeprevir have revolutionised HCV genotype 1 treatment since their introduction. A number of pre-treatment resistance associated amino acid variants (RAVs) and polymorphisms have been associated with reduced response to treatment. Objectives: We measured the prevalence of RAVs/polymorphisms in a PI treatment-naïve HCV genotype 1 Scottish cohort using Sanger sequencing. Study design: Chronically infected, treatment-naïve, HCV genotype 1 patients (n = 146) attending NHS Greater Glasgow and Clyde clinics were investigated for RAVs/polymorphisms to the PIs boceprevir, telaprevir and simeprevir. The NS3/4A region was amplified by nested polymerase chain reaction. The 1.4 kb amplified product was sequenced using an ABI 3710XL DNA sequencer. Sequence analysis was performed using web-based ReCall (beta 2.10). Amino acid positions 36, 41, 43, 54, 55, 80, 109, 122, 155, 156, 168 and 170 were analysed for RAVs/polymorphisms. Results: Overall, 23.29% (34/146) of patients had an RAV or polymorphism detected. Overall, 13.69% (20/146) of patients had HCV virus that contained the Q8 K polymorphism. Other RAVs detected were: V36 M 0.70% (1/146), V36L 0.70% (1/146), T54S 6.85% (10/146), V55A 3.42% (5/146) and V/I170A 0.68% (1/146). Four patients had dual combinations of mutations (T54S + V36L; T54S + V55A and 2 patients with T54S + Q80K). Conclusions: Q80K was the most prevalent baseline polymorphism detected in the Scottish cohort. Simeprevir treatment is not recommended in patients infected with the Q80K genotype 1a variant. This highlights the need for baseline sequencing prior to administration of this drug in this population

No evidence for killer sperm or other selective interactions between human spermatozoa in ejaculates of different males in vitro

This study examines one of the possible mechanisms of sperm competition, i.e. the kamikaze sperm hypothesis. This hypothesis states that sperm from different males interact to incapacitate each other in a variety of ways. We used ejaculates from human donors to compare mixes of semen in vitro from the same or different males. We measured the following parameters: (i) the degree of sperm aggregation, velocity and proportion of morphologically normal sperm after 1 and 3 h incubation in undiluted semen samples, (ii) the proportion of viable sperm plus the same parameters as in (i) in 'swim-up' sperm suspensions after 1 and 3 h incubation, (iii) the degree of self and non-self sperm aggregation using fluorescent dyes to distinguish the sperm of different males, and (iv) the extent of sperm capacitation and acrosome-reacted sperm in mixtures of sperm from the same and different males. We observed very few significant changes in sperm aggregation or performance in mixtures of sperm from different males compared with mixtures from the same male and none that were consistent with previously reported findings. The incapacitation of rival sperm therefore seems an unlikely mechanism of sperm competition in humans

Fast computation by block permanents of cumulative distribution functions of order statistics from several populations

The joint cumulative distribution function for order statistics arising from several different populations is given in terms of the distribution function of the populations. The computational cost of the formula in the case of two populations is still exponential in the worst case, but it is a dramatic improvement compared to the general formula by Bapat and Beg. In the case when only the joint distribution function of a subset of the order statistics of fixed size is needed, the complexity is polynomial, for the case of two populations.Comment: 21 pages, 3 figure

Measurement of the quenching factor of Na recoils in NaI(Tl)

Measurements of the quenching factor for sodium recoils in a 5 cm diameter NaI(Tl) crystal at room temperature have been made at a dedicated neutron facility at the University of Sheffield. The crystal has been exposed to 2.45 MeV mono-energetic neutrons generated by a Sodern GENIE 16 neutron generator, yielding nuclear recoils of energies between 10 and 100 keVnr. A cylindrical BC501A detector has been used to tag neutrons that scatter off sodium nuclei in the crystal. Cuts on pulse shape and time of flight have been performed on pulses recorded by an Acqiris DC265 digitiser with a 2 ns sampling time. Measured quenching factors of Na nuclei range from 19% to 26% in good agreement with other experiments, and a value of 25.2 \pm 6.4% has been determined for 10 keV sodium recoils. From pulse shape analysis, the mean times of pulses from electron and nuclear recoils have been compared down to 2 keVee. The experimental results are compared to those predicted by Lindhard theory, simulated by the SRIM Monte Carlo code, and a preliminary curve calculated by Prof. Akira Hitachi.Comment: 21 pages, 13 figure

Do Multinational enterprises push up wages of domestic firms in the Italian Manufacturing sector?

This paper analyzes the effects of foreign direct investment on wages paid by domestic firms in the Italian manufacturing sector over the period 2002–2007. In particular, the authors investigate the im-pact of multinational enterprises on wages paid by local firms which operate in the same industry, known and horizontal wage spillovers, or have linkages with multinational enterprises in both downstream and upstream industries, known as vertical wage spillovers. By using a large panel dataset, consisting of 551,000 observations, the authors find evidence of wage spillovers only at inter-industry level and, more specifically, for those firms who supply their goods to multinational enterprises, described as backward wage spillovers. Moreover, findings suggest that the wage spillover effect is strongly affected by the technological gap between local and foreign firms: only workers employed in domestic firms with a low-medium technological absorptive capacity seem to benefit from the presence of multinational enterprises in terms of higher wages

Childhood and the politics of scale: Descaling children's geographies?

This is the post-print version of the final published paper that is available from the link below. Copyright @ 2008 SAGE Publications.The past decade has witnessed a resurgence of interest in the geographies of children's lives, and particularly in engaging the voices and activities of young people in geographical research. Much of this growing body of scholarship is characterized by a very parochial locus of interest — the neighbourhood, playground, shopping mall or journey to school. In this paper I explore some of the roots of children's geographies' preoccupation with the micro-scale and argue that it limits the relevance of research, both politically and to other areas of geography. In order to widen the scope of children's geographies, some scholars have engaged with developments in the theorization of scale. I present these arguments but also point to their limitations. As an alternative, I propose that the notion of a flat ontology might help overcome some difficulties around scalar thinking, and provide a useful means of conceptualizing sociospatiality in material and non-hierarchical terms. Bringing together flat ontology and work in children's geographies on embodied subjectivity, I argue that it is important to examine the nature and limits of children's spaces of perception and action. While these spaces are not simply `local', they seldom afford children opportunities to comment on, or intervene in, the events, processes and decisions that shape their own lives. The implications for the substance and method of children's geographies and for geographical work on scale are considered

An Improved Upper Bound for the Ground State Energy of Fermion Lattice Models

We present an improved upper bound for the ground state energy of lattice fermion models with sign problem. The bound can be computed by numerical simulation of a recently proposed family of deformed Hamiltonians with no sign problem. For one dimensional models, we expect the bound to be particularly effective and practical extrapolation procedures are discussed. In particular, in a model of spinless interacting fermions and in the Hubbard model at various filling and Coulomb repulsion we show how such techniques can estimate ground state energies and correlation function with great accuracy.Comment: 5 pages, 5 figures; to appear in Physical Review

The quantitative significance of Syntrophaceae and syntrophic partnerships in methanogenic degradation of crude oil alkanes

Libraries of 16S rRNA genes cloned from methanogenic oil degrading microcosms amended with North Sea crude oil and inoculated with estuarine sediment indicated that bacteria from the genera Smithella (Deltaproteobacteria, Syntrophaceace) and Marinobacter sp. (Gammaproteobacteria) were enriched during degradation. Growth yields and doubling times (36 days for both Smithella and Marinobacter) were determined using qPCR and quantitative data on alkanes, which were the predominant hydrocarbons degraded. The growth yield of the Smithella sp. [0.020 g(cell-C)/g(alkane-C)], assuming it utilized all alkanes removed was consistent with yields of bacteria that degrade hydrocarbons and other organic compounds in methanogenic consortia. Over 450 days of incubation predominance and exponential growth of Smithella was coincident with alkane removal and exponential accumulation of methane. This growth is consistent with Smithella's occurrence in near surface anoxic hydrocarbon degrading systems and their complete oxidation of crude oil alkanes to acetate and/or hydrogen in syntrophic partnership with methanogens in such systems. The calculated growth yield of the Marinobacter sp., assuming it grew on alkanes, was [0.0005 g(cell-C)/g(alkane-C)] suggesting that it played a minor role in alkane degradation. The dominant methanogens were hydrogenotrophs (Methanocalculus spp. from the Methanomicrobiales). Enrichment of hydrogen-oxidizing methanogens relative to acetoclastic methanogens was consistent with syntrophic acetate oxidation measured in methanogenic crude oil degrading enrichment cultures. qPCR of the Methanomicrobiales indicated growth characteristics consistent with measured rates of methane production and growth in partnership with Smithella

Women and Illegal Activities: Gender Differences and Women's Willingness to Comply Over Time

In recent years the topics of illegal activities such as corruption or tax evasion have attracted a great deal of attention. However, there is still a lack of substantial empirical evidence about the determinants of compliance. The aim of this paper is to investigate empirically whether women are more willing to be compliant than men and whether we observe (among women and in general) differences in attitudes among similar age groups in different time periods (cohort effect) or changing attitudes of the same cohorts over time (age effect) using data from eight Western European countries from the World Values Survey and the European Values Survey that span the period from 1981 to 1999. The results reveal higher willingness to comply among women and an age rather than a cohort effect. Working Paper 06-5