Truncation of gene F5L partially masks rescue of vaccinia virus strain MVA growth on mammalian cells by restricting plaque size

Modified vaccinia virus Ankara (MVA) is a candidate vaccine vector that is severely attenuated due to mutations acquired during several hundred rounds of serial passage in vitro. A previous study used marker rescue to produce a set of MVA recombinants with improved replication on mammalian cells. Here, we extended the characterization of these rescued MVA strains and identified vaccinia virus (VACV) gene F5L as a determinant of plaque morphology but not replication in vitro. F5 joins a growing group of VACV proteins that influence plaque formation more strongly than virus replication and which are disrupted in MVA. These defective genes in MVA confound the interpretation of marker rescue experiments designed to map mutations responsible for the attenuation of this important VACV strain.This work was funded by grants to DCT: NHMRC APP1023141 and ARC FT110100310

Estimating cluster-level local average treatment effects in cluster randomised trials with non-adherence

Non-adherence to assigned treatment is a common issue in cluster randomised trials (CRTs). In these settings, the efficacy estimand may be also of interest. Many methodological contributions in recent years have advocated using instrumental variables to identify and estimate the local average treatment effect (LATE). However, the clustered nature of randomisation in CRTs adds to the complexity of such analyses. In this paper, we show that under certain assumptions, the LATE can be estimated via two-stage least squares (TSLS) using cluster-level summaries of outcomes and treatment received. Implementation needs to account for this, as well as the possible heteroscedasticity, to obtain valid inferences. We use simulations to assess the performance of TSLS of cluster-level summaries under cluster-level or individual-level non-adherence, with and without weighting and robust standard errors. We also explore the impact of adjusting for cluster-level covariates and of appropriate degrees of freedom correction for inference. We find that TSLS estimation using cluster-level summaries provides estimates with small to negligible bias and coverage close to nominal level, provided small sample degrees of freedom correction is used for inference, with appropriate use of robust standard errors. We illustrate the methods by re-analysing a CRT in UK primary health settings.Comment: 21 pages, 6 Figure

Simplicity in simplicial phase space

A key point in the spin foam approach to quantum gravity is the implementation of simplicity constraints in the partition functions of the models. Here, we discuss the imposition of these constraints in a phase space setting corresponding to simplicial geometries. On the one hand, this could serve as a starting point for a derivation of spin foam models by canonical quantisation. On the other, it elucidates the interpretation of the boundary Hilbert space that arises in spin foam models. More precisely, we discuss different versions of the simplicity constraints, namely gauge-variant and gauge-invariant versions. In the gauge-variant version, the primary and secondary simplicity constraints take a similar form to the reality conditions known already in the context of (complex) Ashtekar variables. Subsequently, we describe the effect of these primary and secondary simplicity constraints on gauge-invariant variables. This allows us to illustrate their equivalence to the so-called diagonal, cross and edge simplicity constraints, which are the gauge-invariant versions of the simplicity constraints. In particular, we clarify how the so-called gluing conditions arise from the secondary simplicity constraints. Finally, we discuss the significance of degenerate configurations, and the ramifications of our work in a broader setting.Comment: Typos and references correcte

SOCIAL PROBLEMS, BIOMEDICAL ANSWERS? HOW CAUSES OF SOCIAL PROBLEMS AFFECT CHOICE OF SOLUTIONS

With rapid advances in behavioural genetics, scientists are identifying an increasing array of genetic influences on human behaviour. Public misconceptions about the function of genes often lead to the oversimplification of the role of genes in behaviour (Dar-Nimrod & Heine, 2011). To date, no study has systematically investigated whether simply learning about genetic causes of behaviour affects people’s preferred solutions to problematic behaviours. The present research program includes three studies that were designed to examine the psychological effects of exposure to genetic etiology for problematic behaviour, in particular aggression, and investigated how this information influences endorsement of solutions, rating of effectiveness, and support for research funding. It was predicted that compared to a psycho-social etiological emphasis, a genetic etiological emphasis would increase preference for biomedical approaches. Participants read an article outlining the multi-determined nature of aggression, either emphasizing a newly-discovered genetic or an environmental cause of aggression which accounted for behavioural aggression in 30% of those with the predisposition. Across all three studies, the genetic emphasis increased preference for biomedicine compared to a psycho-social emphasis of aggression. In Studies 2 and 3 the psycho-social emphasis also increased preference for socio-behavioural approaches to aggression. These results underscore the importance of considering how media reports of genetic influences on behaviour can meaningfully affect people’s beliefs about treatments and solutions to social issues. In Study 1 and 3, assigning responsibility to genetic or environmental factors for aggression mediates solution preferences and preliminary evidence from Study 3 suggests that coherence of arguments, perceptions about personal responsibility and predispositions increases the effects of the emphasis condition. The effect of emphasis was also discussed in relation to additional variables. Findings from this program of research contribute to best practices for professionals and journalists when conveying genetic research to the public

Generational Status and Views on Nonconforming Gender Expression among Individuals of Mexican Origin

Despite recent change of perspectives and an increase of acceptance of gender nonconformity, the concept of gender still remains a controversial topic. Gender continues to be a developing idea and maintains an influential role in many cultural contexts. Examining facets of gender in various settings can perhaps enlighten our comprehension of such and a further understanding of those who express gender nontraditionally. This study examines the concept of gender in a less traditional stance, exploring views of non-conforming gender expression among generations of Mexican Americans and individuals of Mexican origin. Through analysis of survey data on views of gender nonconformity taken by a university student and faculty population identifying as Mexican American or of Mexican origin, I bring light to the influence that generation of the individual and their hold on traditional views have on the concept of gender in a non-binary framework. I find that there is a significance in the individual’s generational status and their views on non-conforming gender expression among a Mexican Americans and individuals of Mexican decent, showing the higher the generational status the less traditional views held of gender

Cardiovascular Risk Factors and Dehydroepiandrosterone Sulfate Among Latinos in the Boston Puerto Rican Health Study.

Low blood dehydroepiandrosterone sulfate (DHEAS) levels have strong positive associations with stroke and coronary heart disease. However, it is unclear whether DHEAS is independently associated with cardiovascular risk factors. Therefore, we examined the association between cardiovascular risk factors and DHEAS concentration among a high-risk population of Latinos (Puerto Ricans aged 45 to 75 years at baseline) in a cross-sectional analysis of the Boston Puerto Rican Health Study. Of eligible participants, 72% completed baseline interviews and provided blood samples. Complete data were available for 1355 participants. Associations between cardiovascular risk factors (age, sex, total cholesterol, high-density lipid cholesterol, triglycerides, and glucose) and log-transformed DHEAS (μg/dL) were assessed. In robust multivariable regression analyses, DHEAS was significantly inversely associated with age (β = -12.4; 95% CI: -15.2, -9.7; per 5 years), being female (vs. male) (β = -46; 95% CI: -55.3, -36.6), and plasma triglyceride concentration (β = -0.2; 95% CI: -0.3, -0.1; per 10 mg/dL) and was positively associated with total cholesterol and plasma glucose levels (β = 1.8; 95% CI: 0.6, 3 and β = 0.2; 95% CI: 0.04, 0.3, respectively, per 10 mg/dL) after adjustment for smoking, alcohol, and physical activity and for postmenopausal hormone use in women. Estimates were unchanged after adjustment for measures of chronic disease and inflammation. Women exhibited a stronger age-related decline in DHEAS and a positive association with glucose in contrast to findings among men (P interaction < 0.05). In conclusion, in this large study of Latinos with a heavy cardiovascular risk factor burden, we observed significant associations between cardiovascular disease (CVD) risk factors and DHEAS, with variations by sex. These findings improve our understanding of the role DHEAS may play in CVD etiology

Experimental evidence of new tetragonal polymorphs of silicon formed through ultrafast laser-induced confined microexplosion

Ordinary materials can transform into novel phases at extraordinary high pressure and temperature. The recently developed method of ultrashort laser-induced confined microexplosions initiates a non-equilibrium disordered plasma state. Ultra-high quenching rates overcome kinetic barriers to the formation of new metastable phases, which are preserved in the surrounding pristine crystal for subsequent exploitation. Here we demonstrate that confined microexplosions in silicon produce several metastable end phases. Comparison with an ab initio random structure search reveals six energetically competitive potential phases, four tetragonal and two monoclinic structures. We show the presence of bt8 and st12, which have been predicted theoretically previously, but have not been observed in nature or in laboratory experiments. In addition, the presence of the as yet unidentified silicon phase, Si-VIII and two of our other predicted tetragonal phases are highly likely within laser-affected zones. These findings may pave the way for new materials with novel and exotic properties

The emergence of a "digital underclass" in Great Britain and Sweden: changing reasons for digital exclusion

Research into reasons for Internet non-use has been mostly based on one-off cohort studies and focused on single-country contexts. This article shows that motivations for being offline changed between 2005 and 2013 among non- and ex-users in two high-diffusion European countries. Analyses of Swedish and British data demonstrate that non-user populations have become more concentrated in vulnerable groups. While traditional digital divide reasons related to a lack of access and skills remain important, motivational reasons increased in importance over time. The ways in which these reasons gain importance for non- and ex-user groups vary, as do explanations for digital exclusion in the different countries. Effective interventions aimed at tackling digital exclusion need to take into consideration national contexts, changing non-user characteristics, and individual experience with the Internet. What worked a decade ago in a particular country might not work currently in a different or even the same country.</jats:p