The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma

Objectives: To assess whether cervical mediastinoscopy is necessary before radical resection of malignant pleural mesothelioma (MPM). Methods: Patients who underwent radical excision of MPM in a 48-month period were prospectively followed for evidence of disease recurrence and death. Histological evidence of extra pleural lymph node metastases was correlated with survival. Lymph node size at intraoperative lymphadenectomy was correlated with the presence of metastatic tumour. Results: The 55 patients who underwent radical resection (51 extra pleural pneumonectomies and 4 radical pleurectomies) comprised 50 men and 5 women with a median age of 58 years, range 41-70. Histological examination revealed 50 epithelioid, four biphasic and one sarcomatoid histology. Postoperative IMIG T stage was stage I 4, II 11, III 30 and IV 10. Postoperatively the 17 patients with metastases to the extra pleural lymph nodes had significantly shorter survival (median 4.4 months, 95% CI 3.2-5.4) than those without (median survival 16.3 months, 95% CI 11.6-21.0) P=0.012 Kaplan-Meier analysis. Seventy-seven extra pleural lymph nodes without metastases were measured with a mean long axis diameter of 16.9 mm (range 4-55) ; 22 positive nodes had a mean long axis diameter of 15.2 mm (range 6-30). In 15 of the 17 patients with positive extra pleural nodes, the nodes could have been biopsied at cervical mediastinoscopy. Conclusions: This study confirms that extra pleural nodal metastases are related to poor survival. Pathological nodal involvement cannot be predicted from nodal dimensions. These data suggest that all patients being considered for radical resection of MPM should preferentially undergo preoperative cervical mediastinoscopy irrespective of radiological findings. © 2003 Elsevier B.V. All rights reserved.

The effect of extent of local resection on patterns of disease progression in malignant pleural mesothelioma

Background We sought to determine whether or not there are differences in disease progression after radical or nonradical (debulking) surgical procedures for malignant pleural mesothelioma. Methods Over a 49-month period, 132 patients with malignant pleural mesothelioma underwent surgery. Fifty-three underwent extrapleural pneumonectomy and 79 underwent nonradical procedures. Time to evidence of clinical disease progression was recorded, as was the site(s) of that disease. Results One-hundred nineteen patients were evaluable, of which 59% (22 radical; 48 nonradical) had disease progression. Overall 30-day mortality was 8.5% (7.5% radical; 9% nonradical). The median time to overall disease progression was considerably longer after extrapleural pneumonectomy than debulking surgery (319 days vs 197 days, p = 0.019), as was the time to local disease progression (631 days vs 218 days, p = 0.0018). There was no preponderance of earlier stage disease in the radical surgery group. There was a trend toward prolonged survival in those undergoing radical surgery, but no significant difference between the groups (497 days vs 324 days, p = 0.079). In those who had extrapleural pneumonectomy, time-to-disease progression significantly decreased with N2 disease compared with N0/1 involvement (197 days vs 358 days, p = 0.02). Conclusions Extrapleural pneumonectomy may be preferable to debulking surgery in malignant pleural mesothelioma to delay disease progression and give greater control of local disease. Involvement of N2 nodes is associated with accelerated disease progression and is therefore a contraindication to extrapleural pneumonectomy. © 2004 by The Society of Thoracic Surgeons.

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma : clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

Background The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. Methods MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Findings Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. Interpretation In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. Funding Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust. © 2011 Elsevier Ltd.

Biomechanical characteristics of peripheral diabetic neuropathy : a systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure

Background: Diabetic peripheral neuropathy is an important cause of foot ulceration and limb loss. This systematic review and meta-analysis investigated the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and dynamic plantar pressures. Methods: Electronic databases were searched systematically for articles reporting the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and plantar pressures. Searches were restricted to articles published between January 2000 and April 2012. Outcome measures assessed included spatiotemporal parameters, lower limb kinematics, kinetics, muscle activation and plantar pressure. Meta-analyses were carried out on all outcome measures reported by ≥3 studies. Findings: Sixteen studies were included consisting of 382 neuropathy participants, 216 diabetes controls without neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait variables. A high level of heterogeneity was noted between studies. Meta-analysis results suggested a longer stance time and moderately higher plantar pressures in diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot compared to controls. Systematic review of studies suggested potential differences in the biomechanical characteristics (kinematics, kinetics, EMG) of diabetic neuropathy patients. However these findings were inconsistent and limited by small sample sizes.; Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies. Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies.

Continuous positive air pressure treatment for obstructive sleep apnoea patients : effects on sleep quality and quantity as measured by actigraphy

Objectives Actigraphy can reliably assess sleep in healthy adults and be used to estimate total sleep time in suspected obstructive sleep apnoea (OSA) patients. We compared sleep quality for Continuous Positive Air Pressure (CPAP) treated OSA patients and controls, evaluating the impact of stopping CPAP for one night. Methods 11 men, aged 51–75 years (m = 65.6 years), compliant CPAP users, treated for 1–19 years (m = 7.8 years) wore Cambridge Neurotechnology Ltd actiwatches for one night while using CPAP and for one night sleeping without CPAP. A control group of 11 healthy men, aged 63–74 years (m = 64.1 years) slept normally whilst wearing an actiwatch. Subsequent daytime sleepiness was recorded using Karolinska sleepiness scores (KSS). Results Actimetry showed no significant differences between actual sleep time, sleep efficiency, sleep disturbance index or number of wake bouts when comparing OSA participants using CPAP, with controls; there was no difference in subsequent daytime sleepiness, control KSS = 4.21, OSA KSS = 4.17. Without CPAP there was no significant difference in sleep length or sleep onset latency compared with using CPAP, but there was a significant impact on sleep quality as shown by: increased sleep disturbance index from 7.9 to 13.8 [t(10) = 3.510, P < 0.05], decreased percent of actual sleep from 92.05% to 86.15% [t(10) = 3.51, P < 0.05], decreased sleep efficiency from 86.6% to 81% [t(10) = 2.204, P < 0.05] and increased number of wake bouts from 29 to 42.5 [t(10) = 3.877, P < 0.05]. Daytime sleepiness became significantly worse increasing from KSS 4.17 to 6.27 [t(10) = )4.96, P < 0.05]. Conclusion There was no disparity in sleep quality or KSS scores between CPAP treated OSA patients and healthy controls of a similar age. Treated OSA patients obtained quality sleep with no elevated day time sleepiness. However, cessation of treatment for one night caused sleep quality to deteriorate despite a comparable sleep time; the deterioration in sleep quality could explain the increase in daytime sleepiness. OSA patients need to know that even short-term noncompliance with CPAP treatment significantly impairs sleep quality, leading to excessive sleepiness during monotonous tasks such as driving. Actigraphy successfully identified nights of non-compliance in treated OSA patients; but did not differentiate between the sleep of CPAP treated OSA patients and healthy controls.

Visual analog scale and pressure pain threshold for delayed onset muscle soreness assessment

Objectives: To investigate the relationship between two assessments to quantify delayed onset muscle soreness [DOMS]: visual analog scale [VAS] and pressure pain threshold [PPT]. Methods: Thirty-one healthy young men [25.8 ± 5.5 years] performed 10 sets of six maximal eccentric contractions of the elbow flexors with their non-dominant arm. Before and one to four days after the exercise, muscle pain perceived upon palpation of the biceps brachii at three sites [5, 9 and 13 cm above the elbow crease] was assessed by VAS with a 100 mm line [0 = no pain, 100 = extremely painful], and PPT of the same sites was determined by an algometer. Changes in VAS and PPT over time were compared amongst three sites by a two-way repeated measures analysis of variance, and the relationship between VAS and PPT was analyzed using a Pearson product-moment correlation. Results: The VAS increased one to four days after exercise and peaked two days post-exercise, while the PPT decreased most one day post-exercise and remained below baseline for four days following exercise [p < 0.05]. No significant difference among the three sites was found for VAS [p = 0.62] or PPT [p = 0.45]. The magnitude of change in VAS did not significantly correlate with that of PPT [r = −0.20, p = 0.28]. Conclusion: These results suggest that the level of muscle pain is not region-specific, at least among the three sites investigated in the study, and VAS and PPT provide different information about DOMS, indicating that VAS and PPT represent different aspects of pain.

Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM)

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

Chronic activation of the low affinity site of β1-adrenoceptors stimulates haemodynamics but exacerbates pressure-overload cardiac remodelling

Background and Purpose The β1-adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L, respectively), which mediate cardiostimulation. While β1H-adrenoceptor can be blocked by all clinically used β-blockers, β1L-adrenoceptor is relatively resistant to blockade. Thus, chronic β1L-adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H-adrenoceptors. Hence, it is important to determine the potential significance of β1L-adrenoceptors in vivo, particularly in pathological situations. Experimental Approach C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L-adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (-)-CGP12177 (10 mg·kg−1·day−1). Cardiac function was assessed by echocardiography and micromanometry. Key Results (-)-CGP12177 treatment of healthy mice increased heart rate and left ventricular (LV) contractility. (-)-CGP12177 treatment of mice subjected to transverse aorta constriction (TAC), during weeks 4–8 or 4–12 after TAC, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment of mice with TAC also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks of TAC. Conclusions and Implications β1L-adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained β1L-adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure.

Simultaneous estimation of hunting pressure, harvest and hunter success rates using WinBUGS

The use of hierarchical Bayesian spatial models in the analysis of ecological data is increasingly prevalent. The implementation of these models has been heretofore limited to specifically written software that required extensive programming knowledge to create. The advent of WinBUGS provides access to Bayesian hierarchical models for those without the programming expertise to create their own models and allows for the more rapid implementation of new models and data analysis. This facility is demonstrated here using data collected by the Missouri Department of Conservation for the Missouri Turkey Hunting Survey of 1996. Three models are considered, the first uses the collected data to estimate the success rate for individual hunters at the county level and incorporates a conditional autoregressive (CAR) spatial effect. The second model builds upon the first by simultaneously estimating the success rate and harvest at the county level, while the third estimates the success rate and hunting pressure at the county level. These models are discussed in detail as well as their implementation in WinBUGS and the issues arising therein. Future areas of application for WinBUGS and the latest developments in WinBUGS are discussed as well.

Design Pressure Test 2013 Workshop

Design Pressure Test 2013 was a full-day intensive design immersion creative event run on Saturday 3 August 2013, at the QUT Faculty of Creative Industries J Block Design Lab Workshop in Brisbane, Australia, for 25 self-selected high-achieving junior and middle school (year 5-9) students, as part of the Queensland Academies ‘Young Scholars’ Program. Facilitated by tertiary interior design, fashion design and industrial design educators, technicians and six tertiary interior design and fashion design students, the workshop explored design process, environmental impact, the material properties and structural integrity of cardboard, construction techniques, and the production and evaluation of furniture design prototypes. This action research study aimed to facilitate an awareness in young people, of the role and scope of design within our society, the environmental ramifications of design decisions, and the value of design thinking skills in generating strategies to solve basic to complex challenges. It also aimed to investigate the value of collaboration between junior and middle school students, tertiary design educators and students and industry professionals in design awareness, and inspiring post-secondary pathways and idea generation for education. During the creative event, students utilised mathematics skills and developed sketching, making, communication, presentation and collaboration skills to improve their design process, while considering social, cultural and environmental opportunities. Through a series of hands-on collaborative design experiments, participants explored in teams of five, the opportunities available using cardboard as a material – inspiring both functional and aesthetic design solutions. Underpinned by the State Library of Queensland Design Minds Website ‘inquire, ideate and implement’ model of design thinking, the experiments culminated in the development of a detailed client brief, the design and fabrication of a furniture item for seating, and then a team presentation of prototypes to a panel of judges from the professions of architecture, interior design and industrial design, viewed also by parents. The final test for structural integrity was measured by the hoisting down of an adult body weight onto the fabricated seat. The workshop was filmed for the television program ‘Totally Wild’ for dissemination nationally (over 200,000 viewing audience) of the value of design and the Design Minds model to a wider target youth audience.

High pressure in situ diffraction studies of metal–hydrogen systems

“Hybrid” hydrogen storage, where hydrogen is stored in both the solid material and as a high pressure gas in the void volume of the tank can improve overall system efficiency by up to 50% compared to either compressed hydrogen or solid materials alone. Thermodynamically, high equilibrium hydrogen pressures in metal–hydrogen systems correspond to low enthalpies of hydrogen absorption–desorption. This decreases the calorimetric effects of the hydride formation–decomposition processes which can assist in achieving high rates of heat exchange during hydrogen loading—removing the bottleneck in achieving low charging times and improving overall hydrogen storage efficiency of large hydrogen stores. Two systems with hydrogenation enthalpies close to −20 kJ/mol H2 were studied to investigate the hydrogenation mechanism and kinetics: CeNi5–D2 and ZrFe2−xAlx (x = 0.02; 0.04; 0.20)–D2. The structure of the intermetallics and their hydrides were studied by in situ neutron powder diffraction at pressures up to 1000 bar and complementary X-ray diffraction. The deuteration of the hexagonal CeNi5 intermetallic resulted in CeNi5D6.3 with a volume expansion of 30.1%. Deuterium absorption filled three different types of interstices, Ce2Ni2 and Ni4 tetrahedra, and Ce2Ni3 half-octahedra and was accompanied by a valence change for Ce. Significant hysteresis was observed between deuterium absorption and desorption which profoundly decreased on a second absorption cycle. For the Al-modified Laves-type C15 ZrFe2−xAlx intermetallics, deuteration showed very fast kinetics of H/D exchange and resulted in a volume increase of the FCC unit cells of 23.5% for ZrFe1.98Al0.02D2.9(1). Deuterium content, hysteresis of H/D uptake and release, unit cell expansion and stability of the hydrides systematically change with the amount of Al content. In the deuteride D atoms exclusively occupy the Zr2(Fe,Al)2 tetrahedra. Observed interatomic distances are Zr–D = 1.98–2.11; (Fe, Al)–D = 1.70–1.75A˚ . Hydrogenation slightly increases the magnetic moment of the Fe atoms in ZrFe1.98Al0.02 and ZrFe1.96Al0.04 from 1.9 �B at room temperature for the alloy to 2.2 �B for its deuteride.

Wind pressure measurements on a cube subjected to pulsed impinging jet flow

A pulsed impinging jet is used to simulate the gust front of a thunderstorm downburst. This work concentrates on investigating the peak transient loading conditions on a 30 mm cubic model submerged in the simulated downburst flow. The outflow induced pressures are recorded and compared to those from boundary layer and steady wall jet flow. Given that peak winds associated with downburst events are often located in the transient frontal region, the importance of using a non-stationary modelling technique for assessing peak downburst wind loads is highlighted with comparisons.

Synthesis of MgB2 at low temperature and autogenous pressure

High quality, micron-sized interpenetrating grains of MgB2 with high density are produced at low temperatures (~420oC < T < ~500oC) under autogenous pressure by pre-mixing Mg powder and NaBH4 and heating in an Inconel 601 alloy reactor for 5−15 hours. Optimum production of MgB2 with yields greater than 75% occurs for autogenous pressure in the range 1.0 MPa to 2.0 MPa with the reactor at ~500oC. Autogenous pressure is induced by the decomposition of NaBH4 in the presence of Mg and/or other Mg-based compounds. The morphology, transition temperature and magnetic properties of MgB2 are dependent on the heating regime. Significant improvement in physical properties accrues when the reactor temperature is held at 250oC for >20minutes prior to a hold at 500oC.

Pressure state response-based method for evaluating social benefits from smart grid development

In this paper, the inherent mechanism of social benefits associated with smart grid development is examined based on the pressure state response (PSR) model from resource economics. The emerging types of technology brought up by smart grid development are regarded as pressures. The improvements of the performance and efficiency of power system operation, such as the enhanced capability of accommodating renewable energy generation, are regarded as states. The effects of smart grid development on society are regarded as responses. Then, a novel method for evaluating social benefits from smart grid development is presented. Finally, the social benefits from smart grid development in a province in northwest China are carried out by using the developed evaluation system, and reasonable evaluation results are attained.

Time pressure and coworker support mediate the curvilinear relationship between age and occupational well-being

As the proportion of older employees in the workforce is growing, researchers have become increasingly interested in the association between age and occupational well-being. The curvilinear nature of relationships between age and job satisfaction and between age and emotional exhaustion is well-established in the literature, with employees in their late 20s to early 40s generally reporting lower levels of occupational well-being than younger and older employees. However, the mechanisms underlying these curvilinear relationships are so far not well understood due to a lack of studies testing mediation effects. Based on an integration of role theory and research from the adult development and career literatures, this study examined time pressure, work–home conflict, and coworker support as mediators of the relationships between age and job satisfaction and between age and emotional exhaustion. Data came from 771 employees between 17 and 74 years of age in the construction industry. Results showed that employees in their late 20s to early 40s had lower job satisfaction and higher emotional exhaustion than younger and older employees. Time pressure and coworker support fully mediated both the U-shaped relationship between age and job satisfaction and the inversely U-shaped relationship between age and emotional exhaustion. These findings suggest that organizational interventions may help increase the relatively low levels of occupational well-being in certain age groups.