Shuffling of mobile genetic elements (MGEs) in successful healthcare-associated MRSA (HA-MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) CC22 SCCmecIV is a successful hospital-associated (HA-) MRSA, widespread throughout the world, and now the dominant clone in UK hospitals. We have recently shown that MRSA CC22 is a particularly fit clone, and it rose to dominance in a UK hospital at the same time as it began acquiring an increased range of antibiotic resistances. These resistances were not accumulated by individual CC22 isolates, but appear to shuffle frequently between isolates of the MRSA CC22 population. Resistances are often encoded on mobile genetic elements (MGEs) that include plasmids, transposons, bacteriophage and S. aureus pathogenicity islands (SaPIs). Using multi-strain whole genome microarrays, we show that there is enormous diversity of MGE carried within a MRSA CC22 SCCmecIV population, even among isolates from the same hospital and time period. MGE profiles were so variable that they could be used to track the spread of variant isolates within the hospital. We exploited this to show that the majority of patients colonised with MRSA at hospital admission that subsequently became infected were infected with their own colonising isolate. Our studies reveal MGE spread, stability, selection and clonal adaptation to the healthcare setting may be key to the success of HA-MRSA clones, presumably by allowing rapid adaptation to antibiotic exposure and new hosts

Hierarchy stability moderates the effect of status on stress and performance in humans

High social status reduces stress responses in numerous species, but the stress-buffering effect of status may dissipate or even reverse during times of hierarchical instability. In an experimental test of this hypothesis, 118 participants (57.3% female) were randomly assigned to a high- or low-status position in a stable or unstable hierarchy and were then exposed to a social-evaluative stressor (a mock job interview). High status in a stable hierarchy buffered stress responses and improved interview performance, but high status in an unstable hierarchy boosted stress responses and did not lead to better performance. This general pattern of effects was observed across endocrine (cortisol and testosterone), psychological (feeling in control), and behavioral (competence, dominance, and warmth) responses to the stressor. The joint influence of status and hierarchy stability on interview performance was explained by feelings of control and testosterone reactivity. Greater feelings of control predicted enhanced interview performance, whereas increased testosterone reactivity predicted worse performance. These results provide direct causal evidence that high status confers adaptive benefits for stress reduction and performance only when the social hierarchy is stable. When the hierarchy is unstable, high status actually exacerbates stress responses

Beyond the challenge hypothesis: The emergence of the dual-hormone hypothesis and recommendations for future research

The challenge hypothesis makes specific predictions about the association between testosterone and status-seeking behaviors, but the findings linking testosterone to these behaviors are often inconsistent. The dual-hormone hypothesis was developed to help explain these inconsistencies. Specifically, according to this hypothesis, testosterone's association with status-seeking behavior depends on levels of cortisol. Here, we (1) describe the dual-hormone hypothesis in relation to the challenge hypothesis; (2) review recent studies that tested the dual-hormone hypothesis as well as meta-scientific evidence of heterogeneous dual-hormone findings across studies; (3) discuss potential explanations for this heterogeneity, including methodological considerations, contextual factors, and individual differences; and (4) provide recommendations for new work aimed at testing and extending the dual-hormone hypothesis

Testosterone fluctuations in response to a democratic election predict partisan attitudes toward the elected leader

Intergroup competitions such as democratic elections can intensify intergroup polarization and conflict. Partisan attitudes toward the elected leader can also shift from before to after an election, but the biology underlying these attitudinal shifts remains largely unknown. An important factor could be the hormone testosterone, which is theorized to fluctuate during competition and to influence status seeking. In a naturalistic study of 113 registered voters, we measured changes in testosterone levels and attitudes toward the winner of the 2012 US Presidential Election. We found that supporters of the losing candidate (Mitt Romney) showed acute increases in testosterone levels compared to supporters of the winner (Barack Obama) on the evening of Election Day. Supporters of the losing candidate also demonstrated flatter diurnal testosterone slopes on Election Day that persisted up to two days after the election. Furthermore, greater increases in acute testosterone levels and flatter diurnal slopes among supporters of the losing candidate were associated with less positive evaluations of the winning candidate. These testosterone-moderated attitudinal shifts observed in the days after the election showed a directionally similar pattern with a weaker effect size six months later. Finally, we confirmed that the main results were robust to alternative data analytic choices using multiverse specification curve analysis. The findings from this paper suggest that hormonal responses to large-scale intergroup competitions may shape how we perceive our elected leaders, shedding light on the biology of intergroup relations

Experimental testing of grouted connections for offshore substructures: a critical review

Grouted connections have been extensively used in the oil and gas industry for decades, and more recently their application has been extended to the offshore wind industry. Unfortunately plain-pipe grouted connections for large-diameter monopile foundations have recently exhibited clear signs of insufficient axial capacity, resulting in slippage between the transition piece and monopile. Motivated by the emergence of such problems, this paper presents a critical review of the technical literature related to the experimental testing for grouted connections for offshore substructures, covering all the key material and design parameters that influence their capacity, including the confinement provided by pile and sleeve, surface finish, simultaneous bending action, connection length, dynamic loading, early-age cycling during grout curing, grout shrinkage, radial pre-stress and temperature. The review also focuses on the relevance of such parameters for offshore wind applications and addresses what needs to be considered to ensure that their design achieves the desired capacity, behaviour and efficiency

Prediction of wear in grouted connections for offshore wind turbine generators

Insufficient axial capacity of large-diameter plain-pipe grouted connections has recently been observed in offshore wind turbine substructures across Europe. Aimed at understanding the implications of this phenomenon, a campaign of structural condition monitoring was undertaken. The measurements showed significant axial displacements occurring between the transition piece and the monopile, which in turn resulted in a considerable amount of wear. Given the existing lack of technical data on the implications that this relative movement has on the wear of grouted connections, a methodology was developed to quantify the likely risk to the foundation integrity of the wear failure mode. The proposed approach consists of a numerical model which applies the wear rate derived from previous experimental testing to the conditions experienced by typical offshore grouted connections, as indicated by the wind turbine generators' supervisory control and data acquisition systems. The output of this model showed that, for a representative sample of the wind farm substructures analysed as a case study, the accumulated lifetime wear would be minimal in the majority of the grouted connection, i.e. less than 0.4 mm over 75% of the connection, but a much greater loss in thickness, of the order of 4 mm, was predicted at the very top and bottom of the connection. This assessment is based on the assumptions that no significant changes occur in the surrounding environmental conditions and that the degradation in the grouted connection does not significantly affect the dynamic response of the foundation structure over its life span. Importantly, these assumptions may affect the model's predictions in terms of cumulated wear over time, not in terms of identifying the individual connections to be prioritised when performing remedial work, which is indeed the main intended use of the model

Experimental investigation on the development of wear in grouted connections for offshore wind turbine generators

Relative displacements between grout and steel have been observed in grouted connections used for offshore wind turbine substructures, which appear to be linked to the unexpected settlements that have occurred in some offshore wind farms. A literature review has highlighted a lack of understanding of the implications that this relative movement has on the grout wear. Experimentation has therefore been undertaken to determine the influence of various factors on the wear development, including compressive stress, displacement amplitude, surface roughness and the presence of water, looking at conditions typically experienced by offshore grouted connections. These experiments have indicated that wear of the steel and grout surfaces occur, even at low magnitude compressive stresses. The presence of water has the most significant impact on wear rate, being up to 18 times higher than for the equivalent dry condition. The presence of water can also significantly reduce the coefficient of friction to values lower than typically recommended for evaluation of grouted connections. These findings demonstrate that wear of the grouted connection is likely to occur over the life of this type of offshore structures and should therefore be considered when evaluating their integrity and assessing their behaviour

Analysis of operating system diversity for intrusion tolerance

One of the key benefits of using intrusion-tolerant systems is the possibility of ensuring correct behavior in the presence of attacks and intrusions. These security gains are directly dependent on the components exhibiting failure diversity. To what extent failure diversity is observed in practical deployment depends on how diverse are the components that constitute the system. In this paper, we present a study with operating system's (OS's) vulnerability data from the NIST National Vulnerability Database (NVD). We have analyzed the vulnerabilities of 11 different OSs over a period of 18 years, to check how many of these vulnerabilities occur in more than one OS. We found this number to be low for several combinations of OSs. Hence, although there are a few caveats on the use of NVD data to support definitive conclusions, our analysis shows that by selecting appropriate OSs, one can preclude (or reduce substantially) common vulnerabilities from occurring in the replicas of the intrusion-tolerant system