Flupirtine enhances the anti-hyperalgesic effects of morphine in a rat model of prostate bone metastasis

Objective Current treatments for cancer pain are often inadequate, particularly when metastasis to bone is involved. The addition to the treatment regimen of another drug that has a complementary analgesic effect may increase the overall analgesia without the necessity to increase doses, thus avoiding dose-related side effects. This project investigated the synergistic effect of the addition of the potassium channel (KCNQ2–3) modulator flupirtine to morphine treatment in a rat model of prostate cancer-induced bone pain. Design Syngeneic prostate cancer cells were injected into the right tibia of male Wistar rats under anesthesia. This led to expanding tumor within the bone in 2 weeks, together with the concurrent development of hyperalgesia to noxious heat. Paw withdrawal thresholds from noxious heat were measured before and after the maximum non-sedating doses of morphine and flupirtine given alone and in combinations. Dose-response curves for morphine (0.13–5.0 mg/kg ip) and flupirtine (1.25–10.0 mg/kg ip) given alone and in fixed-dose combinations were plotted and subjected to an isobolographic analysis. Results Both morphine (ED50 = 0.74 mg/kg) and flupirtine (ED50 = 3.32 mg/kg) caused dose-related anti-hyperalgesia at doses that did not cause sedation. Isobolographic analysis revealed that there was a synergistic interaction between flupirtine and morphine. Addition of flupirtine to morphine treatment improved morphine anti-hyperalgesia, and resulted in the reversal of cancer-induced heat hyperalgesia. Conclusions These results suggest that flupirtine in combination with morphine may be useful clinically to provide better analgesia at lower morphine doses in the management of pain caused by tumors growing in bone.

Effectiveness of a puppet show on iodine knowledge, attitudes and behaviour of elementary students and the indirect effects on their parents and households in Ho Chi Minh City : a pilot study

Deficiencies in iodine levels have been shown to seriously affect a child’s intellectual development and learning capacity.1 In South-East Asia, iodine deficiency remains a major public health concern. Approximately 30% of the region’s population of 503.6 million have insufficient iodine intake, and only 61% of households have access to iodized salt.1 For this reason, it is necessary to initiate effective, community-based health promotion activities that are targeted toward populations of various ages. A puppet show is one imaginative and entertaining method of health education that has been advocated for use in communicating positive health behaviours to children.2e5 The authors undertook a literature review and found no studies assessing the effectiveness of a puppet show to teach an iodine education programme...

Spatially varying ground motion effects on seismic response of adjacent structures considering soil-structure interaction

Spatial variation of seismic ground motions is caused by incoherence effect, wave passage, and local site conditions. This study focuses on the effects of spatial variation of earthquake ground motion on the responses of adjacent reinforced concrete (RC) frame structures. The adjacent buildings are modeled considering soil-structure interaction (SSI) so that the buildings can be interacted with each other under uniform and non-uniform ground motions. Three different site classes are used to model the soil layers of SSI system. Based on fast Fourier transformation (FFT), spatially correlated non-uniform ground motions are generated compatible with known power spectrum density function (PSDF) at different locations. Numerical analyses are carried out to investigate the displacement responses and the absolute maximum base shear forces of adjacent structures subjected to spatially varying ground motions. The results are presented in terms of related parameters affecting the structural response using three different types of soil site classes. The responses of adjacent structures have changed remarkably due to spatial variation of ground motions. The effect can be significant on rock site rather than clay site.

Geochemistry-based coral palaeoclimate studies and the potential of ‘non-traditional’ (non-massive Porites) corals : recent developments and future progression

Understanding the natural variability of the Earth's climate system and accurately identifying potential anthropogenic influences requires long term, geographically distributed records of key climate indicators, such as temperature and precipitation that extend prior to the last 400. years of the Holocene. Reef corals provide an excellent source of high resolution climate records, and importantly represent the tropical marine environment where palaeoclimate data are urgently required. Recent decades have seen significant improvement in our understanding of coral biomineralisation, the associated uptake of geochemical proxies and methods of identifying and understanding the effects of both early and late, post depositional diagenetic alteration. These processes all have significant implications for interpreting geochemical proxies relevant to palaeoclimatic reconstructions. This paper reviews the current 'state of the art' in terms of coral based palaeoclimate reconstructions and highlights a key remaining problem. The majority of coral based palaeoclimate research has been derived from massive colonies of Porites. However, massive Porites are not globally abundant and may not provide material of a particular age of interest in those regions where they are present. Therefore, there is great potential for alternate coral genera to act as complimentary climate archives. While it remains critical to consider five key factors - vital effects, differential growth morphologies, geochemical heterogeneity in the skeletal ultrastructure, transfer equation selection and diagenetic screening of skeletal material - in order to allow the highest level of accuracy in coral palaeoclimate reconstructions, it is also important to develop alternate taxa for palaeoclimate studies in regions where Porites colonies are absent or rare. Currently as many as nine genera other than Porites have proven at least limited utility in palaeothermometry, most of which are found in the Atlantic/Caribbean region where massive Porites do not exist. Even branching taxa such as Acropora have significant potential to preserve environmental archives. Increasing this capability will greatly expand the number of potential geochemical archives available for longer term temporal records of palaeoclimate.

Investigating the mediating effects of emotional intelligence and coping on problem behaviours in adolescents

This study explored the mediating effect of emotional intelligence (EI) and coping strategies on problem behaviours in Australian adolescents. One hundred and forty-five adolescents (60 boys and 85 girls with a mean age of 12.02 years) completed self-report instruments of EI, stress coping strategies, and problem behaviours. The relationships between Emotional Management and Control and engagement in internalising and externalising behaviours were found to be mediated by the use of non-productive coping strategies. Mediation models of the relationship between problem behaviours and the Understanding Emotions and Emotional Recognition and Expression dimensions were found to be only partially mediated by the engagement in problem-focused and non-productive coping strategies. The results are discussed in regards to how coping strategies utilised in adolescence may produce more or less adaptive patterns of coping during adulthood. The development of emotional abilities may be required to improve coping outcomes for adolescents, which in turn may produce better psychological outcomes for adolescents in the long term.

Audit committee effectiveness : informal processes and behavioural effects

Purpose This paper seeks to investigate the conditions and processes affecting the operation and potential effectiveness of audit committees (ACs), with particular focus on the interaction between the AC, individuals from financial reporting and internal audit functions and the external auditors. Design/methodology/approach A case study approach is employed, based on direct engagement with participants in AC activities, including the AC chair, external auditors, internal auditors, and senior management. Findings The authors find that informal networks between AC participants condition the impact of the AC and that the most significant effects of the AC on governance outcomes occur outside the formal structures and processes. An AC has pervasive behavioural effects within the organization and may be used as a threat, an ally and an arbiter in bringing solutions to issues and conflicts. ACs are used in organizational politics, communication processes and power plays and also affect interpretations of events and cultural values. Research limitations/implications Further research on AC and governance processes is needed to develop better understanding of effectiveness. Longitudinal studies, focusing on the organizational and institutional context of AC operations, can examine how historical events in an organization and significant changes in the regulatory environment affect current structures and processes. Originality/value The case analysis highlights a number of significant factors which are not fully recognised either in theorizing the governance role of ACs or in the development of policy and regulations concerning ACs but which impinge on their governance contribution. They include the importance of informal processes around the AC; its influence on power relations between organizational participants; the relevance of the historical development of governance in an organization; and the possibility that the AC’s impact on governance may be greatest in non-routine situations.

Systematic review of pharmacologic and non-pharmacologic interventions to manage cognitive alterations after chemotherapy for breast cancer

Purpose Cognitive alterations are reported in breast cancer patients receiving chemotherapy. This has adverse effects on patients’ quality of life and function. This systematic review investigates the effectiveness of pharmacologic and non-pharmacologic interventions to manage cognitive alterations associated with breast cancer treatment. Methods Medline via EBSCOhost, CINAHL and Cochrane CENTRAL were searched for the period January 1999 to May 2014 for prospective randomized controlled trials related to the management of chemotherapy-associated cognitive alterations. Included studies investigated the management of chemotherapy-associated cognitive alterations and used subjective or objective measures in patients with breast cancer during or after chemotherapy. Two authors independently extracted data and assessed the risk of bias. Results Thirteen studies involving 1138 participants were included. Overall, the risk of bias for the 13 studies were either high (n=11) or unclear (n=2). Pharmacologic interventions included psychostimulants (n=4), epoetin alfa (n=1), and Ginkgo biloba (n=1). Non-pharmacologic interventions were cognitive training (n=5) and physical activity (n=2). Pharmacologic agents were ineffective except for self-reported cognitive function in an epoetin alfa study. Cognitive training interventions demonstrated benefits in self-reported cognitive function, memory, verbal function and language and orientation/attention. Physical activity interventions were effective in improving executive function and self-reported concentration. Conclusion Current evidence does not favor the pharmacologic management of cognitive alterations associated with breast cancer treatment. Cognitive training and physical activity interventions appear promising, but additional studies are required to establish their efficacy. Further research is needed to overcome methodological shortfalls such as heterogeneity in participant characteristics and non-standardized neuropsychological outcome measures.

Impact of gender-focused human resource management on performance : the mediating effects of gender diversity

Gender-focused human resource policies and practices signal an organization’s perspective on gender diversity. The signal produces perceptions that the organization values gender diversity leading to a gender-diverse workforce. In turn, a gender-diverse workforce provides a firm with a competitive advantage which should result in higher performance. This paper tests the mediating effects of gender diversity (at non-management and management levels) in the relationship between gender-focused policies and practices and performance. The findings indicate that non-management gender diversity partially mediates the relationship between gender-focused policies and practices and productivity, and management gender diversity partially mediates the relationship between gender-focused policies and practices and perceived market performance. The results have several theoretical, research and practical implications.

Assessing the welfare effects of microfinance in Vietnam : empirical results from a quasi-experimental survey

This article analyses the effects of NGO microfinance programmes on household welfare in Vietnam. Data on 470 households across 25 villages were collected using a quasi-experimental survey approach to overcome any self-selection bias. The sample was designed so that member households of microfinance programmes were compared with non-member households with similar characteristics. The analysis shows no significant effects of participation in NGO microfinance on household welfare, proxied by income and consumption per adult equivalent.

Does school type affect cognitive and non-cognitive development in children? Evidence from Australian primary schools

This paper investigates the effects of primary school choices on cognitive and non-cognitive development in children using data from the Longitudinal Study of Australian Children (LSAC). We militate against the measurement problems that are associated with individual unobserved heterogeneity by exploiting the richness of LSAC data and applying contemporary econometric approaches. We find that sending children to Catholic or other independent primary schools has no significant effect on their cognitive and non-cognitive outcomes. The literature now has evidence from three different continents that the returns to attending Catholic primary schools are no different than public schools.

Study of the novel non-xanthine heterocyclic compound GU 285 as a potent non-selective adenosine receptor antagonist in the rat

The novel pyrazolo[3,4-d]pyrimidine compound GU285 (4-amino-6-alpha-carbamoylethylthio-1- phenylpyrazolo[3,4-d]pyrimidine, CAS 134896-40-5) was examined for its ability (1) to inhibit binding of adenosine (ADO) receptor ligands in rat brain membranes, (2) to antagonise functional responses to ADO agonists in rat right and left atria and coronary resistance vessels, and (3) to reduce the fall in heart rate and arterial blood pressure produced by the ADO A1 agonist N6-cyclopentyladenosine (CPA) in the intact, anaesthetized rat. GU285 competitively inhibited binding of the ADO A1 agonist [3H]-R-N6-phenylisopropyladenosine (R-PIA) yielding a Ki value of 11 (7-18) nmol.l-1 (geometric mean +/- 95% Cl). When assayed against the ADO A2A selective agonist [3H]-2-[p-(2-carboxyethyl)- phenethylamino]-5'-N-ethylcarboxamidoadenosine, (CGS21680), a Ki of 15 (10-24) nmol.l-1 was obtained. In spontaneously beating right atria, GU285 competitively antagonized negative chronotropic effects of R-PIA with a pA2 of 8.7 +/- 0.3 and in electrically paced left atria, GU285 competitively antagonized negative inotropic effects of R-PIA with a pA2 of 9.0 +/- 0.1. In the potassium-arrested, perfused rat heart GU285 (1 mumol.l-1) antagonized only the high sensitivity, ADO A2B mediated component of the biphasic relaxation of the coronary vasculature produced by NECA. The low sensitivity component was unchanged. GU285 (1 mumol.kg-1) antagonized the negative chronotropic and hypotensive effects of the adenosine A1 agonist CPA in anaesthetized rats, producing a 10-fold rightward shift in the dose-response relationship. These data demonstrate that in the rat, GU285 is a potent, non-selective adenosine receptor antagonist that maintains its activity in vivo.

Transitioning to energy efficient vehicles: An analysis of the potential rebound effects and subsequent impact upon emissions

Given the shift toward energy efficient vehicles (EEVs) in recent years, it is important that the effects of this transition are properly examined. This paper investigates some of these effects by analyzing annual kilometers traveled (AKT) of private vehicle owners in Stockholm in 2008. The difference in emissions associated with EEV adoption is estimated, along with the effect of a congestion-pricing exemption for EEVs on vehicle usage. Propensity score matching is used to compare AKT rates of different vehicle owner groups based on the treatments of: EEV ownership and commuting across the cordon, controlling for confounding factors such as demographics. Through this procedure, rebound effects are identified, with some EEV owners found to have driven up to 12.2% further than non-EEV owners. Although some of these differences could be attributed to the congestion-pricing exemption, the results were not statistically significant. Overall, taking into account lifecycle emissions of each fuel type, average EEV emissions were 50.5% less than average non-EEV emissions, with this reduction in emissions offset by 2.0% due to rebound effects. Although it is important for policy-makers to consider the potential for unexpected negative effects in similar transitions, the overall benefit of greatly reduced emissions appears to outweigh any rebound effects present in this case study.

Family-based programmes for preventing smoking by children and adolescents (Review)

Background There is evidence that family and friends influence children's decisions to smoke. Objectives To assess the effectiveness of interventions to help families stop children starting smoking. Search methods We searched 14 electronic bibliographic databases, including the Cochrane Tobacco Addiction Group specialized register, MEDLINE, EMBASE, PsycINFO, CINAHL unpublished material, and key articles' reference lists. We performed free-text internet searches and targeted searches of appropriate websites, and hand-searched key journals not available electronically. We consulted authors and experts in the field. The most recent search was 3 April 2014. There were no date or language limitations. Selection criteria Randomised controlled trials (RCTs) of interventions with children (aged 5-12) or adolescents (aged 13-18) and families to deter tobacco use. The primary outcome was the effect of the intervention on the smoking status of children who reported no use of tobacco at baseline. Included trials had to report outcomes measured at least six months from the start of the intervention. Data collection and analysis We reviewed all potentially relevant citations and retrieved the full text to determine whether the study was an RCT and matched our inclusion criteria. Two authors independently extracted study data for each RCT and assessed them for risk of bias. We pooled risk ratios using a Mantel-Haenszel fixed effect model. Main results Twenty-seven RCTs were included. The interventions were very heterogeneous in the components of the family intervention, the other risk behaviours targeted alongside tobacco, the age of children at baseline and the length of follow-up. Two interventions were tested by two RCTs, one was tested by three RCTs and the remaining 20 distinct interventions were tested only by one RCT. Twenty-three interventions were tested in the USA, two in Europe, one in Australia and one in India. The control conditions fell into two main groups: no intervention or usual care; or school-based interventions provided to all participants. These two groups of studies were considered separately. Most studies had a judgement of 'unclear' for at least one risk of bias criteria, so the quality of evidence was downgraded to moderate. Although there was heterogeneity between studies there was little evidence of statistical heterogeneity in the results. We were unable to extract data from all studies in a format that allowed inclusion in a meta-analysis. There was moderate quality evidence family-based interventions had a positive impact on preventing smoking when compared to a no intervention control. Nine studies (4810 participants) reporting smoking uptake amongst baseline non-smokers could be pooled, but eight studies with about 5000 participants could not be pooled because of insufficient data. The pooled estimate detected a significant reduction in smoking behaviour in the intervention arms (risk ratio [RR] 0.76, 95% confidence interval [CI] 0.68 to 0.84). Most of these studies used intensive interventions. Estimates for the medium and low intensity subgroups were similar but confidence intervals were wide. Two studies in which some of the 4487 participants already had smoking experience at baseline did not detect evidence of effect (RR 1.04, 95% CI 0.93 to 1.17). Eight RCTs compared a combined family plus school intervention to a school intervention only. Of the three studies with data, two RCTS with outcomes for 2301 baseline never smokers detected evidence of an effect (RR 0.85, 95% CI 0.75 to 0.96) and one study with data for 1096 participants not restricted to never users at baseline also detected a benefit (RR 0.60, 95% CI 0.38 to 0.94). The other five studies with about 18,500 participants did not report data in a format allowing meta-analysis. One RCT also compared a family intervention to a school 'good behaviour' intervention and did not detect a difference between the two types of programme (RR 1.05, 95% CI 0.80 to 1.38, n = 388). No studies identified any adverse effects of intervention. Authors' conclusions There is moderate quality evidence to suggest that family-based interventions can have a positive effect on preventing children and adolescents from starting to smoke. There were more studies of high intensity programmes compared to a control group receiving no intervention, than there were for other compairsons. The evidence is therefore strongest for high intensity programmes used independently of school interventions. Programmes typically addressed family functioning, and were introduced when children were between 11 and 14 years old. Based on this moderate quality evidence a family intervention might reduce uptake or experimentation with smoking by between 16 and 32%. However, these findings should be interpreted cautiously because effect estimates could not include data from all studies. Our interpretation is that the common feature of the effective high intensity interventions was encouraging authoritative parenting (which is usually defined as showing strong interest in and care for the adolescent, often with rule setting). This is different from authoritarian parenting (do as I say) or neglectful or unsupervised parenting.

Novel non-linear elastic structural analysis with generalised transverse element loads using a refined finite element

In the finite element modelling of structural frames, external loads such as wind loads, dead loads and imposed loads usually act along the elements rather than at the nodes only. Conventionally, when an element is subjected to these general transverse element loads, they are usually converted to nodal forces acting at the ends of the elements by either lumping or consistent load approaches. In addition, it is especially important for an element subjected to the first- and second-order elastic behaviour, to which the steel structure is critically prone to; in particular the thin-walled steel structures, when the stocky element section may be generally critical to the inelastic behaviour. In this sense, the accurate first- and second-order elastic displacement solutions of element load effect along an element is vitally crucial, but cannot be simulated using neither numerical nodal nor consistent load methods alone, as long as no equilibrium condition is enforced in the finite element formulation, which can inevitably impair the structural safety of the steel structure particularly. It can be therefore regarded as a unique element load method to account for the element load nonlinearly. If accurate displacement solution is targeted for simulating the first- and second-order elastic behaviour on an element on the basis of sophisticated non-linear element stiffness formulation, the numerous prescribed stiffness matrices must indispensably be used for the plethora of specific transverse element loading patterns encountered. In order to circumvent this shortcoming, the present paper proposes a numerical technique to include the transverse element loading in the non-linear stiffness formulation without numerous prescribed stiffness matrices, and which is able to predict structural responses involving the effect of first-order element loads as well as the second-order coupling effect between the transverse load and axial force in the element. This paper shows that the principle of superposition can be applied to derive the generalized stiffness formulation for element load effect, so that the form of the stiffness matrix remains unchanged with respect to the specific loading patterns, but with only the magnitude of the loading (element load coefficients) being needed to be adjusted in the stiffness formulation, and subsequently the non-linear effect on element loadings can be commensurate by updating the magnitude of element load coefficients through the non-linear solution procedures. In principle, the element loading distribution is converted into a single loading magnitude at mid-span in order to provide the initial perturbation for triggering the member bowing effect due to its transverse element loads. This approach in turn sacrifices the effect of element loading distribution except at mid-span. Therefore, it can be foreseen that the load-deflection behaviour may not be as accurate as those at mid-span, but its discrepancy is still trivial as proved. This novelty allows for a very useful generalised stiffness formulation for a single higher-order element with arbitrary transverse loading patterns to be formulated. Moreover, another significance of this paper is placed on shifting the nodal response (system analysis) to both nodal and element response (sophisticated element formulation). For the conventional finite element method, such as the cubic element, all accurate solutions can be only found at node. It means no accurate and reliable structural safety can be ensured within an element, and as a result, it hinders the engineering applications. The results of the paper are verified using analytical stability function studies, as well as with numerical results reported by independent researchers on several simple frames.

Effects of anticoagulants on outcome of femoral neck fracture surgery

PURPOSE To review records of 330 patients who underwent surgery for femoral neck fractures with or without preoperative anticoagulation therapy. METHODS Medical records of 235 women and 95 men aged 48 to 103 years (mean, 81.6; standard deviation [SD], 13.1) who underwent surgery for femoral neck fractures with or without preoperative anticoagulation therapy were reviewed. 30 patients were on warfarin, 105 on aspirin, 28 on clopidogrel, and 167 were controls. The latter 3 groups were combined as the non-warfarin group and compared with the warfarin group. Hospital mortality, time from admission to surgery, length of hospital stay, return to theatre, and postoperative complications (wound infection, deep vein thrombosis, and pulmonary embolism) were assessed. RESULTS The warfarin and control groups were significantly younger than the clopidogrel and aspirin groups (80.8 vs. 80.0 vs. 84.2 vs. 83.7 years, respectively, p<0.05). 81% of the patients underwent surgery within 48 hours of admission. The overall mean time from admission to surgery was 1.8 days; it was longer in the warfarin than the aspirin, clopidogrel, and control groups (3.3 vs. 1.8 vs. 1.6 vs. 1.6 days, respectively, p<0.001). The mean length of hospital stay was 17.5 (SD, 9.6; range, 3-54) days. The overall hospital mortality was 3.9%; it was 6.7% in the warfarin group, 3.8% in the aspirin group, 3.6% in the clopidogrel group, and 3.6% in the control group (p=0.80). Four patients returned to theatre for surgery: one in the warfarin group for washout of a haematoma, 2 in the aspirin group for repositioning of a mal-fixation and for debridement of wound infection, and one in the control group for debridement of wound infection. The warfarin group did not differ significantly from non-warfarin group in terms of postoperative complication rate (6.7% vs. 2.7%, p=0.228) and the rate of return to theatre (3.3% vs. 1%, p=0.318). CONCLUSION It is safe to continue aspirin and clopidogrel prior to surgical treatment for femoral neck fracture. The risk of delaying surgery outweighs the peri-operative bleeding risk.