Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell lung cancer

INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of >/=200; scale 0-300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of >/=200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non-small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Fabrication of optochemical and electrochemical sensors using thin films of porphyrin and phthalocyanine derivatives

This paper describes the fabrication of thin films of porphyrin and metallophthalocyanine derivatives on different substrates for the optochemical detection of HCl gas and electrochemical determination of L-cysteine (CySH). Solid state gas sensor for HCl gas was fabricated by coating meso-substituted porphyrin derivatives on glass slide and examined optochemical sensing of HCl gas. The concentration of gaseous HCl was monitored from the changes in the absorbance of Soret band. Among the different porphyrin derivatives, meso- tetramesitylporphyrin (MTMP) coated film showed excellent sensitivity towards HCl and achieved a detection limit of 0.03ppm HCl. Further, we have studied the self-assembly of 1,8,15,22-tetraaminometallophthalocyanine (4α-MTAPc; M = Co and Ni) from DMF on GC electrode. The CVs for the self-assembled monolayers (SAMs) of 4α-CoIITAPc and 4α-NiIITAPc show two pairs of well-defined redox couple corresponding to metal and ring. Using the 4α-CoIITAPc SAM modified electrode, sensitive and selective detection of L-cysteine was demonstrated. Further, the SAM modified electrode also successfully separates the oxidation potentials of AA and CySH with a peak separation of 320mV.

How innovation and R&D happen in the upstream oil & gas industry : insights from a global survey

Few would disagree that the upstream oil & gas industry has become more technology-intensive over the years. But how does innovation happen in the industry? Specifically, what ideas and inputs flow from which parts of the sector׳s value network, and where do these inputs go? And how do firms and organizations from different countries contribute differently to this process? This paper puts forward the results of a survey designed to shed light on these questions. Carried out in collaboration with the Society of Petroleum Engineers (SPE), the survey was sent to 469 executives and senior managers who played a significant role with regard to R&D and/or technology deployment in their respective business units. A total of 199 responses were received from a broad range of organizations and countries around the world. Several interesting themes and trends emerge from the results, including: (1) service companies tend to file considerably more patents per innovation than other types of organization; (2) over 63% of the deployed innovations reported in the survey originated in service companies; (3) neither universities nor government-led research organizations were considered to be valuable sources of new information and knowledge in the industry׳s R&D initiatives, and; (4) despite the increasing degree of globalization in the marketplace, the USA still plays an extremely dominant role in the industry׳s overall R&D and technology deployment activities. By providing a detailed and objective snapshot of how innovation happens in the upstream oil & gas sector, this paper provides a valuable foundation for future investigations and discussions aimed at improving how R&D and technology deployment are managed within the industry. The methodology did result in a coverage bias within the survey, however, and the limitations arising from this are explored.

Health and guardianship law : guardianship and administration application in the matter of MDC [2014] QCAT 338

The recent decision of the Queensland Civil and Administrative Tribunal (QCAT) in Guardianship and administration application in the matter of MDC [2014] QCAT 338, provides an important ruling on the limits of who can be appointed as an enduring power of attorney under the Powers of Attorney Act 1998 (Qld). In particular, the tribunal adopted a broad interpretation of the term "health provider" when considering the limits on who can be appointed as an enduring power of attorney under the legislation...

Reconciliation and Early Childhood Education for Sustainability : Broadening the Environmental Paradigm

The uptake of sustainability initiatives in early childhood education curricula continues to gain momentum in Australia and internationally. Growing awareness about the fragility of natural environments in local and global contexts, along with prioritising sustainability in educational policy, has resulted in more broad-scale responses to sustainability in early years settings. To address issues of sustainability, many childcare centres and schools focus on environmental initiatives such as garden projects, recycling and water conservation. While important, such initiatives respond to just one dimension of sustainability. With expanding focus on sustainability initiatives in early childhood education, it is timely to consider why the environmental dimension receives the most attention and what this means for social, political and economic areas of concern.

Paternal postnatal depressive symptoms, infant sleeping and feeding behaviors, and rigid parental regulation : a correlational study

Paternal postnatal depression (PND) is now recognized as a serious and prevalent problem, associated with poorer well-being and functioning of all family members. Aspects of infant temperament, sleeping and feeding perceived by parents as problematic are associated with maternal PND, however, less is known about paternal PND. This study investigated depressive symptoms (Edinburgh postnatal depression scale (EPDS)) in 219 fathers of infants aged from 1 to 24 weeks (median 7.0 weeks). Infant predictor variables were sleeping problems, feeding problems and both mother and father reported temperament. Control variables were partner’s support, other support and life events. Rigidity of parenting beliefs regarding infant regulation was also measured as a potential moderating factor. Infant feeding difficulties were associated with paternal depressive symptoms, subsuming the variance associated with both sleep problems and temperament. This relationship was not moderated by regulation beliefs. It was concluded that infant feeding is important to fathers. Fathers of infants with feeding difficulties may not be able to fulfill their idealized construction of involved fatherhood. Role incongruence may have an etiological role in paternal PND.

The long-term health consequences of child physical abuse, emotional abuse, and neglect : a systematic review and meta-analysis

Background Child sexual abuse is considered a modifiable risk factor for mental disorders across the life course. However the long-term consequences of other forms of child maltreatment have not yet been systematically examined. The aim of this study was to summarise the evidence relating to the possible relationship between child physical abuse, emotional abuse, and neglect, and subsequent mental and physical health outcomes. Methods and Findings A systematic review was conducted using the Medline, EMBASE, and PsycINFO electronic databases up to 26 June 2012. Published cohort, cross-sectional, and case-control studies that examined non-sexual child maltreatment as a risk factor for loss of health were included. All meta-analyses were based on quality-effects models. Out of 285 articles assessed for eligibility, 124 studies satisfied the pre-determined inclusion criteria for meta-analysis. Statistically significant associations were observed between physical abuse, emotional abuse, and neglect and depressive disorders (physical abuse [odds ratio (OR) = 1.54; 95% CI 1.16–2.04], emotional abuse [OR = 3.06; 95% CI 2.43–3.85], and neglect [OR = 2.11; 95% CI 1.61–2.77]); drug use (physical abuse [OR = 1.92; 95% CI 1.67–2.20], emotional abuse [OR = 1.41; 95% CI 1.11–1.79], and neglect [OR = 1.36; 95% CI 1.21–1.54]); suicide attempts (physical abuse [OR = 3.40; 95% CI 2.17–5.32], emotional abuse [OR = 3.37; 95% CI 2.44–4.67], and neglect [OR = 1.95; 95% CI 1.13–3.37]); and sexually transmitted infections and risky sexual behaviour (physical abuse [OR = 1.78; 95% CI 1.50–2.10], emotional abuse [OR = 1.75; 95% CI 1.49–2.04], and neglect [OR = 1.57; 95% CI 1.39–1.78]). Evidence for causality was assessed using Bradford Hill criteria. While suggestive evidence exists for a relationship between maltreatment and chronic diseases and lifestyle risk factors, more research is required to confirm these relationships. Conclusions This overview of the evidence suggests a causal relationship between non-sexual child maltreatment and a range of mental disorders, drug use, suicide attempts, sexually transmitted infections, and risky sexual behaviour. All forms of child maltreatment should be considered important risks to health with a sizeable impact on major contributors to the burden of disease in all parts of the world. The awareness of the serious long-term consequences of child maltreatment should encourage better identification of those at risk and the development of effective interventions to protect children from violence.

Potential role of bioactive lipids in the development of non-antibody mediated transfusion-related acute lung injury (TRALI)

Transfusion-related acute lung injury (TRALI) has been the leading cause of transfusion-related morbidity and mortality in the UK and the USA in recent years. A threshold mechanism of TRALI has been proposed in which both patient factors (type and/or severity of clinical insult) and blood product factors (strength and/or concentration of antibodies or biological response modifiers) interact to surpass a threshold for TRALI development (Bux et al. Br J Haematol; 2007; 136: 788-99). The risk of developing antibody-mediated TRALI has been minimised by the introduction of risk-reduction strategies such as limiting the use of plasma from female donors. In contrast, there are no strategies currently in place to mitigate the development of non-antibody mediated TRALI as the mechanisms remain largely undefined. Previous studies have implicated non-polar lipids such as arachidonic acid and various species of hydroxyeicosatetranoic acid (HETE) in the development of non-antibody mediated TRALI (Silliman et al. Transfusion; 2011; 51: 2549-54), however the contribution of these lipids to the development of an inflammatory response in TRALI is poorly understood.

Associations between early shared music activities in the home and later child outcomes : findings from the Longitudinal Study of Australian Children

The benefits of early shared book reading between parents and children have long been established,yet the same cannot be said for early shared music activities in the home. This study investigated the parent–child home music activities in a sample of 3031 Australian children participating in Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) study. Frequency of shared home music activities was reported by parents when children were 2–3 years and a range of social, emotional,and cognitive outcomes were measured by parent and teacher report and direct testing two years later when children were 4–5 years old. A series of regression analyses (controlling for a set of important socio-demographic variables) found frequency of shared home music activities to have a small significant partial association with measures of children’s vocabulary, numeracy, attentional and emotional regulation, and prosocial skills. We then included both book reading and shared home music activities in the same models and found that frequency of shared home music activities maintained small partial associations with measures of prosocial skills, attentional regulation, and numeracy. Our findings suggest there may be a role for parent-child home music activities in supporting children’s development.

The desirability of depoliticization: Compliance in the international climate regime

The Kyoto Protocol is remarkable among global multilateral environmental agreements for its efforts to depoliticize compliance. However, attempts to create autonomous, arm’s length and rule-based compliance processes with extensive reliance on putatively neutral experts were only partially realized in practice in the first commitment period from 2008 to 2012. In particular, the procedurally constrained facilitative powers vested in the Facilitative Branch were circumvented, and expert review teams (ERTs) assumed pivotal roles in compliance facilitation. The ad hoc diplomatic and facilitative practices engaged in by these small teams of technical experts raise questions about the reliability and consistency of the compliance process. For the future operation of the Kyoto compliance system, it is suggested that ERTs should be confined to more technical and procedural roles, in line with their expertise. There would then be greater scope for the Facilitative Branch to assume a more comprehensive facilitative role, safeguarded by due process guarantees, in accordance with its mandate. However, if – as appears likely – the future compliance trajectories under the United Nations Framework Convention on Climate Change will include a significant role for ERTs without oversight by the Compliance Committee, it is important to develop appropriate procedural safeguards that reflect and shape the various technical and political roles these teams currently play.

Tourism advertisement management and effective tools in tourism industry

The definition of tourism “is the travel for recreational, leisure, family or business purposes, usually of a limited duration. Tourism is commonly associated with trans-national travel, but may also refer to travel to another location within the same country”. Tourism as an industry, in today’s modern language is a means of global communication between nations and travelers of all countries, introducing them to the various cultures and societies abroad, as well there history, ancient, historical sites, and languages. Hence, advertising overall has become a tool of necessity in this ever-growing global industry. Given that, tourism is a part of the infrastructure of any country’s economy the growth and development of tourism is of great importance. Advertising plays a vital and is a crucial tool in developing the countries tourism by attractively presenting the nations points-of-interests, historical and cultural. Advertising has a central role in expanding this industry, generating economic growth in this area, as well as creating direct and indirect employment, but most importantly a creative innovating competition in the national and international travel industry. Importantly, to achieve a successful tourist industry, the Travel Agencies and governmental offices of the Ministry’s of Tourism and Business must work hand-in-hand to attain these goals. This article shows the impact of the various media and advertising methods used in tourism, which assisted in identifying the correct tool for expanding the country’s industry of tourism. The results of this study illustrated that the appropriate tools for promotional strategies to attract domestic and foreign traveler’s, found to be the most effective were, handbook, internet advertising, TV, brochures, newspapers

Learning through modelling in the primary years

Many nations are highlighting the need for a renaissance in the mathematical sciences as essential to the well-being of all citizens (e.g., Australian Academy of Science, 2006; 2010; The National Academies, 2009). Indeed, the first recommendation of The National Academies’ Rising Above the Storm (2007) was to vastly improve K–12 science and mathematics education. The subsequent report, Rising Above the Gathering Storm Two Years Later (2009), highlighted again the need to target mathematics and science from the earliest years of schooling: “It takes years or decades to build the capability to have a society that depends on science and technology . . . You need to generate the scientists and engineers, starting in elementary and middle school” (p. 9). Such pleas reflect the rapidly changing nature of problem solving and reasoning needed in today’s world, beyond the classroom. As The National Academies (2009) reported, “Today the problems are more complex than they were in the 1950s, and more global. They’ll require a new educated workforce, one that is more open, collaborative, and cross-disciplinary” (p. 19). The implications for the problem solving experiences we implement in schools are far-reaching. In this chapter, I consider problem solving and modelling in the primary school, beginning with the need to rethink the experiences we provide in the early years. I argue for a greater awareness of the learning potential of young children and the need to provide stimulating learning environments. I then focus on data modelling as a powerful means of advancing children’s statistical reasoning abilities, which they increasingly need as they navigate their data-drenched world.

Multi-parametric hydrogels support 3D in vitro bioengineered microenvironment models of tumour angiogenesis

Tumour microenvironment greatly influences the development and metastasis of cancer progression. The development of three dimensional (3D) culture models which mimic that displayed in vivo can improve cancer biology studies and accelerate novel anticancer drug screening. Inspired by a systems biology approach, we have formed 3D in vitro bioengineered tumour angiogenesis microenvironments within a glycosaminoglycan-based hydrogel culture system. This microenvironment model can routinely recreate breast and prostate tumour vascularisation. The multiple cell types cultured within this model were less sensitive to chemotherapy when compared with two dimensional (2D) cultures, and displayed comparative tumour regression to that displayed in vivo. These features highlight the use of our in vitro culture model as a complementary testing platform in conjunction with animal models, addressing key reduction and replacement goals of the future. We anticipate that this biomimetic model will provide a platform for the in-depth analysis of cancer development and the discovery of novel therapeutic targets.

The use of ecosystem services valuation in Australian coastal zone management

The use and influence of ecosystem services valuation in management decision-making, particularly as it relates to coastal zone management, remains largely unexplored in the academic literature. A recent Australia-wide survey of decision-makers involved in coastal zone management examined if, how and to what extent economic valuation of coastal and marine ecosystem services is used in, and influences, decision-making in Australia. The survey also identified a set of cases where economic valuation of ecosystem services was used for decision-making, and reasons why economic values may or may not be considered in the decision-making process. This paper details the method and results from this survey. Overall, there is strong empirical evidence that economic valuation of ecosystem services is used, but with important variation across coastal and marine management contexts. However, the impact of ecosystem services valuation on policy appears to be globally weak.