Gene network and proteomic analyses of cardiac responses to pathological and physiological stress

Background—The molecular mechanisms underlying similarities and differences between physiological and pathological left ventricular hypertrophy (LVH) are of intense interest. Most previous work involved targeted analysis of individual signaling pathways or screening of transcriptomic profiles. We developed a network biology approach using genomic and proteomic data to study the molecular patterns that distinguish pathological and physiological LVH. Methods and Results—A network-based analysis using graph theory methods was undertaken on 127 genome-wide expression arrays of in vivo murine LVH. This revealed phenotype-specific pathological and physiological gene coexpression networks. Despite >1650 common genes in the 2 networks, network structure is significantly different. This is largely because of rewiring of genes that are differentially coexpressed in the 2 networks; this novel concept of differential wiring was further validated experimentally. Functional analysis of the rewired network revealed several distinct cellular pathways and gene sets. Deeper exploration was undertaken by targeted proteomic analysis of mitochondrial, myofilament, and extracellular subproteomes in pathological LVH. A notable finding was that mRNA–protein correlation was greater at the cellular pathway level than for individual loci. Conclusions—This first combined gene network and proteomic analysis of LVH reveals novel insights into the integrated pathomechanisms that distinguish pathological versus physiological phenotypes. In particular, we identify differential gene wiring as a major distinguishing feature of these phenotypes. This approach provides a platform for the investigation of potentially novel pathways in LVH and offers a freely accessible protocol (http://sites.google.com/site/cardionetworks) for similar analyses in other cardiovascular diseases.

Fatigue cracking from stress concentration in mild steel

Pulsating; tension fatigue tests have been carried out on edge notched specimens of a mild steel. An electrical potential drop technique was used to determine the number of cycles taken to initiate cracks and the rate at which the cracks grew across the specimen. The results could be described by the range of stress intensity factor, which for crack initiation was modified to take account of the notch root radius. Analysis of elastic stress distributions at cracks and notches and models of plasticity at crack tips are used to discuss the results. Limited evidence in the literature indicates that the fracture mechanics approach may provide a general description of crack initiation and growth in notched specimens, and a simple graphical method of calculating fatigue lives is described. The results are used to illustrate the effects of specimen size and geometry on the fatigue life of notched specimens. The relevance of the work to the assessment of the significance of defects in welds is discussed.

Weight loss strategies, stress, and cognitive function:supervised versus unsupervised dieting

The early stages of dieting to lose weight have been associated with neuro-psychological impairments. Previous work has not elucidated whether these impairments are a function solely of unsupported or supported dieting. Raised cortico-steroid levels have been implicated as a possible causal mechanism. Healthy, overweight, pre-menopausal women were randomised to one of three conditions in which they dieted either as part of a commercially available weight loss group, dieted without any group support or acted as non-dieting controls for 8 weeks. Testing occurred at baseline and at 1, 4 and 8 weeks post baseline. During each session, participants completed measures of simple reaction time, motor speed, vigilance, immediate verbal recall, visuo-spatial processing and (at Week 1 only) executive function. Cortisol levels were gathered at the beginning and 30 min into each test session, via saliva samples. Also, food intake was self-recorded prior to each session and fasting body weight and percentage body fat were measured at each session. Participants in the unsupported diet condition displayed poorer vigilance performance (p=0.001) and impaired executive planning function (p=0.013) (along with a marginally significant trend for poorer visual recall (p=0.089)) after 1 week of dieting. No such impairments were observed in the other two groups. In addition, the unsupported dieters experienced a significant rise in salivary cortisol levels after 1 week of dieting (p<0.001). Both dieting groups lost roughly the same amount of body mass (p=0.011) over the course of the 8 weeks of dieting, although only the unsupported dieters experienced a significant drop in percentage body fat over the course of dieting (p=0.016). The precise causal nature of the relationship between stress, cortisol, unsupported dieting and cognitive function is, however, uncertain and should be the focus of further research. © 2005 Elsevier Ltd. All rights reserved.

Perspective work on optical fibre sensors

Optical fibre based sensors are transforming industry by permitting monitoring in hitherto inaccessible environments or measurement approaches that cannot be reproduced using conventional electronic sensors. A multitude of techniques have been developed to render the fibres sensitive to a wide range of parameters including: temperature, strain, pressure (static and dynamic), acceleration, rotation, gas type, and specific biochemical species. Constructed entirely of glass or polymer material, optical fibre devices like fibre gratings offer the properties: low loss, dielectric construction, small size, multiplexing, and so on [1-3]. In this paper, the authors will show the latest developing industrial applications, using polymer optical fibre (POF) devices, and comparing their performance with silica optical fibre devices. The authors address two pressing commercial requirements. The first concerns the monitoring of fuel level in civil aircraft. There is a strong motivation in the aerospace industry to move away from electrical sensors, especially in the fuel system. This is driven by the need to eliminate potential ignition hazards, the desire to reduce cabling weight and the need to mitigate the effects of lightning strikes in aircraft where the conventional metallic skin is increasingly being replaced by composite materials. In this case, the authors have developed pressure sensors based on a diaphragm in which a polymer fibre Bragg grating (POFBG) has been embedded [3]. These devices provide high pressure sensitivity enabling level measurement in the mm range. Also, it has developed an approach incorporating several such sensors which can compensate for temperature drifts and is insensitive to fluid density. Compared with silica fibre-based sensors, their performance is highly enhanced. Initial results have attracted the interest of Airbus from UK, who is keen to explore the potential of optical technology in commercial aircraft. The second concerns the monitoring of acoustic signals and vibration in the subsea environment, for applications in geophysical surveying and security (detection of unwanted craft or personnel). There is strong motivation to move away from electrical sensors due to the bulk of the sensor and associated cabling and the impossibility of monitoring over large distances without electrical amplification. Optical approaches like optical hydrophones [5] offer a means of overcoming these difficulties. In collaboration with Kongsberg from Norway, the authors will exploit the sensitivity improvements possible by using POF instead of silica fibre. These improvements will arise as a result of the much more compliant nature of POF compared to silica fibre (3 GPa vs 72 GPa, respectively). Essentially, and despite the strain sensitivity of silica and POFBGs being very similar, this renders the POF much more sensitive to the applied stress resulting from acoustic signals or vibration. An alternative way of viewing this is that the POF is better impedance-matched to the surrounding environment (water for the intended applications), because although its impedance is higher than that of water, it is nearly an order of magnitude smaller than that of silica. Finally, other future industrial applications will be presented and discussed, showing the vast range of the optical fiber devices in sensing applications.

Stress, burnout and coping strategies in the emergency and intensive care hospital departments

Doctors and nurses working at the accident and emergency (A&E), and intensive care departments are at risk of burnout. They often spend substantial time in intense interactions with other people, centered on patients? health problems (physical, psychological and social) that may lead to feelings of anger, anxiety and frustration, and eventually to burnout. Burnout is a syndrome of emotional exhaustion, depersonalization and reduced personal accomplishment (Maslach & Jackson, 1981) The purpose of this chapter is to assess work stressors, burnout and stress-coping mechanisms among doctors and nurses at the A&E and intensive care departments. A quantitative design using the survey approach was used to collect data from a sample of 200 participants with a response rate of 71% (n=154) Work stressors were associated with burnout in both doctors and nurses. Workload was the most salient work stressor in the sample. Nurses experienced more stress (M=1.5, SD=0.4) than doctors (M=1.2, SD=0.4) in all the work stressor variables examined. The A&E department was reported as more stressful than the intensive care department. Avoidance-oriented and task-oriented coping were the most and the least frequently reported coping strategies respectively. Additionally, only emotion-oriented coping strategy was significantly different between doctors and nurses, and this strategy was also significantly positively correlated with all the variables in the adapted nursing stress scale, and the three burnout variables. Death and dying was most strongly correlated with emotion-oriented coping. This chapter provides an assessment of stress, burnout and coping experienced by both doctors and nurses within the A&E and intensive care departments. Methods that may mitigate stress in these environments may be adequate staffing, supportive management, stress management programs, as well as improvement in communication strategies between doctors and nurses.

Well-structured teams and the buffering of hospital employees from stress

Membership in well-structured teams, which show clarity in team and individual goals, meet regularly, and recognize diverse skills of their members, is known to reduce stress. This study examined how membership of well-structured teams was associated with lower levels of strain, when testing a work stressors-to-strains relationship model across the three levels of team structure, namely well-structured, poorly structured (do not fulfill all the criteria of well-structured teams) and no team. The work stressors tested, were quantitative overload and hostile environment, whereas strains were measured through job satisfaction and intention to leave job. This investigation was carried out on a random sample of 65,142 respondents in acute/specialist National Health Service hospitals across the UK. Using multivariate analysis of variance, statistically significant differences between means across the three groups of team structure, with mostly moderate effect sizes, were found for the study variables. Those in well-structured teams have the highest levels of job satisfaction and the least intention to leave job. Multigroup structural equation modelling confirmed the model's robustness across the three groups of team structure. Work stressors explained 45%, 50% and 65% of the variance of strains for well-structured, poorly structured and no team membership, respectively. An increase of one standard deviation in work stressors, resulted in an increase in 0.67, 0.70 and 0.81 standard deviations in strains for well-structured, poorly structured and no team membership, respectively. This investigation is an eye-opener for hospitals to work towards achieving well-structured teams, as this study shows weaker stressor-to-strain relationships for members of these teams.