Cytochrome p450 1b1, a new keystone in gene-environment interactions related to human head and neck cancer?

Alcohol consumption and tobacco smoking are major causes of head and neck cancers, and regional differences point to the importance of research into gene-environment interactions. Much interest has been focused on polymorphisms of CYP1A1 and of GSTM1 and GSTT1, but a number of studies have not demonstrated significant effects. This has mostly been ascribed to small sample sizes. In general, the impact of polymorphisms of metabolic enzymes appears inconsistent, with some reports of weak-to-moderate associations, and with others of no elevation of risks. The classical cytochrome P450 isoenzyme considered for metabolic activation of polycyclic aromatic hydrocarbons (PAH) is CYP1A1. A new member of the CYP1 family, CYP1B1, was cloned in 1994, currently representing the only member of the CYP1B subfamily. A number of single nucleotide polymorphisms of the CYP1B1 gene have been reported. The amino acid substitutions Val432Leu (CYP1B1*3) and Asn453Ser (CYP1B1*4), located in the heme binding domain of CYP1B1, appear as likely candidates to be linked with biological effects. CYP1B1 activates a wide range of PAH, aromatic and heterocyclic amines. Very recently, the CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squamous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has pointed to interactive effects. This provides new molecular evidence that tobacco smoke-specific compounds relevant to head and neck carcinogenesis are metabolically activated through CYP1B1 and is consistent with a major pathogenetic relevance of PAH as ingredients of tobacco smoke.

Using textual analysis with Concept Inventories to identify root causes of misconceptions

Engineers must have deep and accurate conceptual understanding of their field and Concept inventories (CIs) are one method of assessing conceptual understanding and providing formative feedback. Current CI tests use Multiple Choice Questions (MCQ) to identify misconceptions and have undergone reliability and validity testing to assess conceptual understanding. However, they do not readily provide the diagnostic information about students’ reasoning and therefore do not effectively point to specific actions that can be taken to improve student learning. We piloted the textual component of our diagnostic CI on electrical engineering students using items from the signals and systems CI. We then analysed the textual responses using automated lexical analysis software to test the effectiveness of these types of software and interviewed the students regarding their experience using the textual component. Results from the automated text analysis revealed that students held both incorrect and correct ideas for certain conceptual areas and provided indications of student misconceptions. User feedback also revealed that the inclusion of the textual component is helpful to students in assessing and reflecting on their own understanding.

What is the relationship between the term 'ADHD' and the object it purports to represent?

This paper addresses the question: what is the relationship between the term ADHD, and the object it purports to represent? While the most familiar linguistic position—Referential Theory— suggests that the term constitute an etymological peg corresponding to a particular part of nature, there are other, arguably more sophisticated, philosophical approaches that point to an altogether more complex relationship. These approaches do not assume that ‘behaviour disorders’, such as ADHD, are objective facts of nature, facts to which words can simply be adhered. Using the work of Wittgenstein, the intention here is to use the philosophy of language to destabilise, not just the relationship between the term ADHD and the idea to which it applies, but also the coherence of the notion of ADHD itself.

Passenger segmentation using smart card data

Transit passenger market segmentation enables transit operators to target different classes of transit users for targeted surveys and various operational and strategic planning improvements. However, the existing market segmentation studies in the literature have been generally done using passenger surveys, which have various limitations. The smart card (SC) data from an automated fare collection system facilitate the understanding of the multiday travel pattern of transit passengers and can be used to segment them into identifiable types of similar behaviors and needs. This paper proposes a comprehensive methodology for passenger segmentation solely using SC data. After reconstructing the travel itineraries from SC transactions, this paper adopts the density-based spatial clustering of application with noise (DBSCAN) algorithm to mine the travel pattern of each SC user. An a priori market segmentation approach then segments transit passengers into four identifiable types. The methodology proposed in this paper assists transit operators to understand their passengers and provides them oriented information and services.

The culture of young women's drinking: Implications for developing effective policing strategies. Report to National Drug Strategy Law Enforcement Committee

Alcohol-related mortality and morbidity represents a substantial financial burden on communities across the world. Adolescence and young adulthood is a peak period for heavy episodic alcohol consumption, with over a third of all people aged 14-19 years having been at risk of acute alcoholrelated harm at least once in the previous 12 months (Australian Institute of Health and Welfare [AIHW], 2011). Excessive alcohol consumption has long been seen as a male problem; however, a gradual shift towards a social acceptance of female drunkenness has narrowed the gap in drinking quantity and style between men and women (Grucza, Bucholz, Rice, & Bierut, 2008). The presented data point to the vulnerability of women to the consequences of acute alcohol intoxication and indicate that alcohol-related offending by women is on the rise. Taken together, these findings reveal that alcohol-related harms and aggression for young women are becoming more prevalent and problematic. This report addressed these issues from a policing perspective...

Differential segmentation responses to an alcohol social marketing program

Objective This study seeks establish whether meaningful subgroups exist within a 14-16 year old adolescent population and if these segments respond differently to the Game On: Know Alcohol (GOKA) intervention, a school-based alcohol social marketing program. Methodology This study is part of a larger cluster randomized controlled evaluation of the Game On: Know Alcohol (GOKA) program implemented in 14 schools in 2013/2014. TwoStep cluster analysis was conducted to segment 2114 high school adolescents (14-16 years old) on the basis of 22 demographic, behavioral and psychographic variables. Program effects on knowledge, attitudes, behavioral intentions, social norms, expectancies and refusal self-efficacy of identified segments was subsequently examined. Results Three segments were identified: (1) Abstainers (2) Bingers (3) Moderate Drinkers. Program effects varied significantly across segments. The strongest positive change effects post participation were observed for the Bingers, while mixed effects were evident for Moderate Drinkers and Abstainers. Conclusions These findings provide preliminary empirical evidence supporting application of social marketing segmentation in alcohol education programs. Development of targeted programs that meet the unique needs of each of the three identified segments is indicated to extend the social marketing footprint in alcohol education.

Algorithm of medication review in frail older people: Focus on minimizing the use of high-risk medications

Aim Frail older people typically suffer several chronic diseases, receive multiple medications and are more likely to be institutionalized in residential aged care facilities. In such patients, optimizing prescribing and avoiding use of high-risk medications might prevent adverse events. The present study aimed to develop a pragmatic, easily applied algorithm for medication review to help clinicians identify and discontinue potentially inappropriate high-risk medications. Methods The literature was searched for robust evidence of the association of adverse effects related to potentially inappropriate medications in older patients to identify high-risk medications. Prior research into the cessation of potentially inappropriate medications in older patients in different settings was synthesized into a four-step algorithm for incorporation into clinical assessment protocols for patients, particularly those in residential aged care facilities. Results The algorithm comprises several steps leading to individualized prescribing recommendations: (i) identify a high-risk medication; (ii) ascertain the current indications for the medication and assess their validity; (iii) assess if the drug is providing ongoing symptomatic benefit; and (iv) consider withdrawing, altering or continuing medications. Decision support resources were developed to complement the algorithm in ensuring a systematic and patient-centered approach to medication discontinuation. These include a comprehensive list of high-risk medications and the reasons for inappropriateness, lists of alternative treatments, and suggested medication withdrawal protocols. Conclusions The algorithm captures a range of different clinical scenarios in relation to potentially inappropriate medications, and offers an evidence-based approach to identifying and, if appropriate, discontinuing such medications. Studies are required to evaluate algorithm effects on prescribing decisions and patient outcomes.

Parents as co-researchers at home: Using an observational method to document young children’s use of technology

This paper discusses the use of observational video recordings to document young children’s use of technology in their homes. Although observational research practices have been used for decades, often with video-based techniques, the participant group in this study (i.e., very young children) and the setting (i.e., private homes), provide a rich space for exploring the benefits and limitations of qualitative observation. The data gathered in this study point to a number of key decisions and issues that researchers must face in designing observational research, particularly where non-researchers (in this case, parents) act as surrogates for the researcher at the data collection stage. The involvement of parents and children as research videographers in the home resulted in very rich and detailed data about children’s use of technology in their daily lives. However, limitations noted in the dataset (e.g., image quality) provide important guidance for researchers developing projects using similar methods in future. The paper provides recommendations for future observational designs in similar settings and/or with similar participant groups.

Tumour islet Foxp3+ T-cell infiltration predicts poor outcome in nonsmall cell lung cancer

The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis. Tumour- and stroma-infiltrating CD3+, CD8+ and forkhead box P3 (Foxp3)+ T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined. There was a positive association between overall survival and increased CD8+ TI/S ratio (hazard ratio (HR) for death 0.44, p<0.001) but an inverse relationship between Foxp3+ TI/S ratio and overall survival (HR 4.86, p<0.001). Patients with high CD8+ islet (HR 0.48, p<0.001) and Foxp3+ stromal (HR 0.23, p<0.001) counts had better survival, whereas high CD3+ and CD8+ stromal counts and high Foxp3+ islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8+ TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3+ TI/S ratio was associated with worse survival (HR 3.91, p<0.001). Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC.

Adaptive optical flow for person tracking

Person tracking systems are dependent on being able to locate a person accurately across a series of frames. Optical flow can be used to segment a moving object from a scene, provided the expected velocity of the moving object is known; but successful detection also relies on being able segment the background. A problem with existing optical flow techniques is that they don’t discriminate the foreground from the background, and so often detect motion (and thus the object) in the background. To overcome this problem, we propose a new optical flow technique, that is based upon an adaptive background segmentation technique, which only determines optical flow in regions of motion. This technique has been developed with a view to being used in surveillance systems, and our testing shows that for this application it is more effective than other standard optical flow techniques.

They also serve who only stand and wait

Purpose Waiting for service by customers is an important problem for many financial service marketers. Two new approaches are proposed. First, customer evaluation of the service is increased with an ambient scent. Second a cognitive variable is identified which different iates customers by the way they value time so that they can be segmented. Methodology Pretests included focus groups which highlighted financial services and a pilot test were foll owed by a main sample of 607 subjects. Structural equation modelling and multivariate analysis of covariance were used for analysis. Findings A cognitive variable, the need for time management can be used, together with demographic and customer net worth data, to segment a customer base. Two environmental interventions, music and scent, can increase customer satisfaction among customers kept waiting in a line. Research implications Two original approaches to a rapidly growing service marketing problem are identified. Practical implications Service contact points can reduce incidence of "queue rage" and enhance customer satisfaction by either or both of two simple modifications to the service environment or a preventive strategy of offering targeted customers an alternative. Originality A new method of segmentation and a new environmental intervention are proposed .

Business process modeling : perceived benefits

The process-centered design of organizations and information systems is globally seen as an appropriate response to the increased economic pressure on organizations. At the methodological core of process-centered management is process modeling. However, business process modeling in large initiatives can be a time-consuming and costly exercise, making it potentially difficult to convince executive management of its benefits. To date, and despite substantial interest and research in the area of process modeling, the understanding of the actual benefits of process modeling in academia and practice is limited. To address this gap, this paper explores the perception of benefits derived from process modeling initiatives, as reported through a global Delphi study. The study incorporates the views of three groups of stakeholders – academics, practitioners and vendors. Our findings lead to the first identification and ranking of 19 unique benefits associated with process modeling. The study in particular found that process modeling benefits vary significantly between practitioners and academics. We argue that these variations may point to a dangerous disconnect between research projects and practical demands.

Fashion as consumer entrepreneurship : emergent risk culture, social network markets, and the launch of 'Vogue' in China

China has a reputation as an economy based on utility: the large-scale manufacture of low-priced goods. But useful values like functionality, fitness for purpose and efficiency are only part of the story. More important are what Veblen called ‘honorific’ values, arguably the driving force of development, change and value in any economy. To understand the Chinese economy therefore, it is not sufficient to point to its utilitarian aspect. Honorific status-competition is a more fundamental driver than utilitarian cost-competition. We argue that ‘social network markets’ are the expression of these honorific values, relationships and connections that structure and coordinate individual choices. This paper explores how such markets are developing in China in the area of fashion and fashion media. These, we argue, are an expression of ‘risk culture’ for high-end entrepreneurial consumers and producers alike, providing a stimulus to dynamic innovation in the arena of personal taste and comportment, as part of an international cultural system based on constant change. We examine the launch of Vogue China in 2005, and China’s reception as a fashion player among the international editions of Vogue, as an expression of a ‘decisive moment’ in the integration of China into an international social network market based on honorific values.

The criminalisation of medical mistakes in Canada : a review

The issue of health professionals facing criminal charges of manslaughter or criminal negligence causing death or grievous bodily harm as a result of alleged negligence in their professional practice was thrown into stark relief by the recent acquittal of four physicians accused of mismanaging Canada’s blood system in the early 1980s. Stories like these, as well as international reports detailing an increase in the numbers of physicians being charged with (and in some cases convicted of) serious criminal offences as the result of alleged negligence in their professional practice, have resulted in some anxiety about the apparent increase in the incidence of such charges and their appropriateness in the healthcare context. Whilst research has focused on the incidence, nature and appropriateness of criminal charges against health professionals, particularly physicians, for alleged negligence in their professional practice in the United Kingdom, the United States, Japan, and New Zealand, the Canadian context has yet to be examined. This article examines the Canadian context and how the criminal law is used to regulate the negligent acts or omissions of a health care professional in the course of their professional practice. It also assesses the appropriateness of such use. It is important at this point to state that the analysis in this article does not focus on those, fortunately few, cases where a health professional has intentionally killed his or her patients but rather when patients’ deaths or grievous injuries were allegedly as a result of that health professional’s negligent acts or omissions when providing health services to that patient.

New insights into rebound effects : theory and empirical evidence

The main objective of the thesis is to seek insights into the theory, and provide empirical evidence of rebound effects. Rebound effects reduce the environmental benefits of environmental policies and household behaviour changes. In particular, win-win demand side measures, in the form of energy efficiency and household consumption pattern changes, are seen as ways for households and businesses to save money and the environment. However, these savings have environmental impacts when spent, which are known as rebound effects. This is an area that has been widely neglected by policy makers. This work extends the rebound effect literature in three important ways, (1) it incorporates the potential for variation of rebound effects with household income level, (2) it enables the isolation of direct and indirect effects for cases of energy efficient technology adoption, and examines the relationship between these two component effects, and (3) it expands the scope of rebound effect analysis to include government taxes and subsidies. MACROBUTTON HTMLDirect Using a case study approach it is found that the rebound effect from household consumption pattern changes targeted at electricity is between 5 and 10%. For consumption pattern changes with reduced vehicle fuel use, the rebound effect is in the order of 20 to 30%. Higher income households in general are found to have a lower total rebound effect; however the indirect effect becomes relatively more significant at higher household income levels. In the win-lose case of domestic photovoltaic electricity generation, it is demonstrated that negative rebound effects can occur, which can potentially amplify the environmental benefits of this action. The rebound effect from a carbon tax, which occurs due to the re-spending of raised revenues, was found to be in the range of 11-32%. Taxes and transfers between households of different income levels also have environmental implications. For example, a more progressive tax structure, with increased low income welfare payments is likely to increase greenhouse gas emissions. Subsidies aimed at encouraging environmentally friendly consumption habits are also subject to rebound effects, as they constitute a substitution of government expenditure for household expenditure. For policy makers, these findings point to the need to incorporate rebound effects in the environmental policy evaluation process.’