Phosphorylation of the androgen receptor is associated with reduced survival in hormonerefractory prostate cancer patients

Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (<i>P</i>=0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (<i>P</i>=0.014), and an increase in expression of pAkt<sup>473</sup> and pAR<sup>210</sup> were associated with decreased disease-specific survival (<i>P</i>=0.0019 and 0.0015, respectively). Protein expression of pAkt<sup>473</sup> and pAR<sup>210</sup> also strongly correlated (<i>P</i><0.001, c.c.=0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target

Size and emotion or depth and emotion? Evidence, using Matryoshka (Russian) dolls, of children using physical depth as a proxy for emotional charge

Background: The size and emotion effect is the tendency for children to draw people and other objects with a positive emotional charge larger than those with a negative or neutral charge. Here we explored the novel idea that drawing size might be acting as a proxy for depth (proximity).Methods: Forty-two children (aged 3-11 years) chose, from 2 sets of Matryoshka (Russian) dolls, a doll to represent a person with positive, negative or neutral charge, which they placed in front of themselves on a sheet of A3 paper. Results: We found that the children used proximity and doll size, to indicate emotional charge. Conclusions: These findings are consistent with the notion that in drawings, children are using size as a proxy for physical closeness (proximity), as they attempt with varying success to put positive charged items closer to, or negative and neutral charge items further away from, themselves

International Study of the Epidemiology of Paediatric Trauma : PAPSA Research Study

Objectives: Trauma is a significant cause of morbidity and mortality worldwide. The literature on paediatric trauma epidemiology in low- and middle-income countries (LMICs) is limited. This study aims to gather epidemiological data on paediatric trauma. Methods: This is a multicentre prospective cohort study of paediatric trauma admissions, over 1 month, from 15 paediatric surgery centres in 11 countries. Epidemiology, mechanism of injury, injuries sustained, management, morbidity and mortality data were recorded. Statistical analysis compared LMICs and high-income countries (HICs). Results: There were 1377 paediatric trauma admissions over 31 days; 1295 admissions across ten LMIC centres and 84 admissions across five HIC centres. Median number of admissions per centre was 15 in HICs and 43 in LMICs. Mean age was 7 years, and 62% were boys. Common mechanisms included road traffic accidents (41%), falls (41%) and interpersonal violence (11%). Frequent injuries were lacerations, fractures, head injuries and burns. Intra-abdominal and intra-thoracic injuries accounted for 3 and 2% of injuries. The mechanisms and injuries sustained differed significantly between HICs and LMICs. Median length of stay was 1 day and 19% required an operative intervention; this did not differ significantly between HICs and LMICs. No mortality and morbidity was reported from HICs. In LMICs, in-hospital morbidity was 4.0% and mortality was 0.8%. Conclusion: The spectrum of paediatric trauma varies significantly, with different injury mechanisms and patterns in LMICs. Healthcare structure, access to paediatric surgery and trauma prevention strategies may account for these differences. Trauma registries are needed in LMICs for future research and to inform local policy

Intimate Partner Violence During COVID-19 Restrictions: A Study of 30 Countries From the I-SHARE Consortium

Intimate partner violence (IPV) causes substantial physical and psychological trauma. Restrictions introduced in response to the COVID-19 pandemic, including lockdowns and movement restrictions, may exacerbate IPV risk and reduce access to IPV support services. This cross-sectional study examines IPV during COVID-19 restrictions in 30 countries from the International Sexual HeAlth and REproductive Health (I-SHARE) study conducted from July 20th, 2020, to February, 15th, 2021. IPV was a primary outcome measure adapted from a World Health Organization multicountry survey. Mixed-effects modeling was used to determine IPV correlates among participants stratified by cohabitation status. The sample included 23,067 participants from 30 countries. A total of 1,070/15,336 (7.0%) participants stated that they experienced IPV during COVID-19 restrictions. A total of 1,486/15,336 (9.2%) participants stated that they had experienced either physical or sexual partner violence before the restrictions, which then decreased to 1,070 (7.0%) after the restrictions. In general, identifying as a sexual minority and experiencing greater economic vulnerability were associated with higher odds of experiencing IPV during COVID-19 restrictions, which were accentuated among participants who were living with their partners. Greater stringency of COVID-19 restrictions and living in urban or semi-urban areas were associated with lower odds of experiencing IPV in some settings. The I-SHARE data suggest a substantial burden of IPV during COVID-19 restrictions. However, the restrictions were correlated with reduced IPV in some settings. There is a need for investing in specific support systems for survivors of IPV during the implementation of restrictions designed to contain infectious disease outbreaks

Testing of Lead Extrusion Damping Devices Undergoing Representative Earthquake Velocities

In recent years, significant research has been undertaken into the development of lead-extrusion damping technology. The high force-to-volume (HF2V) devices developed at the University of Canterbury have been the subject of much of this research. However, while these devices have undergone a limited range of velocity testing, limitations in test equipment has meant that they have never been tested at representative earthquake velocities. Such testing is important as the peak resistive force provided by the dampers under large velocity spikes is an important design input that must be known for structural applications. This manuscript presents the high-speed testing of HF2V devices with quasi-static force capacities of 250-300kN. These devices have been subjected to peak input velocities of approximately 200mm/s, producing peak resistive forces of approximately 350kN. The devices show stable hysteretic performance, with slight force reduction during high-speed testing due to heat build-up and softening of the lead working material. This force reduction is recovered following cyclic loading as heat is dissipated and the lead hardens again. The devices are shown to be only weakly velocity dependent, an advantage in that they do not deliver large forces to the connecting elements and surrounding structure if larger than expected response velocities occur. This high-speed testing is an important step towards uptake as it provides important information to designers

High force-to-volume extrusion dampers and shock absorbers for civil infrastructure

The ability to dissipate structural energy from seismic, wind and impact loads in a controlled and repeatable manner is essential to maintaining structural integrity for a range of large environmental loads. Extrusion based damping technology is a promising method of achieving these design requirements and is already widely used in base isolation applications. However, the large size of current devices prevents several unique implementations limiting their widespread use. This research develops high force-to-volume extrusion dampers small enough in volume for use in typical structural connections. Re-centering extrusion-based devices extend the technology to high impact loading applications. Design, analysis and experimental verification has been undertaken on lead extrusion dampers sufficiently compact to allow direct placement into universal column sections nominally 350mm deep (W14). Peak force levels up to 450kN with strokes up to 50mm are developed with an optimal (almost fully rectangular) hysteresis loop. Shock absorbers for high force impact loading applications with some recentering capability are developed, with stiffness values up to 3.6 MN/m, and force levels up to 300-400kN. These latter devices have significant potential for industrial structural impact loading applications, such as moorings of large ships. The overall results indicate that maximum energy dissipation with high force/volume relationships can be developed and characterized for lead extrusion damper