Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis.

INTRODUCTION: The dichotomization of non-small cell carcinoma (NSCLC) subtype into squamous (SQCC) and adenocarcinoma (ADC) has become important in recent years and is increasingly required with regard to management. The aim of this study was to determine the utility of a panel of commercially available antibodies in refining the diagnosis on small biopsies and also to determine whether cytologic material is suitable for somatic EGFR genotyping in a prospectively analyzed series of patients undergoing investigation for suspected lung cancer. METHODS: Thirty-two consecutive cases of NSCLC were first tested using a panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, 34betaE12, and a D-PAS stain for mucin, to determine their value in refining diagnosis of NSCLC. After this test phase, two further pathologists independently reviewed the cases using a refined panel that excluded 34betaE12 because of its low specificity for SQCC, and refinement of diagnosis and concordance were assessed. Ten cases of ADC, including eight derived from cytologic samples, were sent for EGFR mutation analysis. RESULTS: There was refinement of diagnosis in 65% of cases of NSCLC to either SQCC or ADC in the test phase. This included 10 of 13 cases where cell pellets had been prepared from transbronchial needle aspirates. Validation by two further pathologists with varying expertise in lung pathology confirmed increased refinement and concordance of diagnosis. All samples were adequate for analysis, and they all showed a wild-type EGFR genotype. CONCLUSION: A panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, and a D-PAS stain for mucin increases diagnostic accuracy and agreement between pathologists when faced with refining a diagnosis of NSCLC to SQCC or ADC. These small samples, even cell pellets derived from transbronchial needle aspirates, seem to be adequate for EGFR mutation analysis.

An analysis of the determinants of job satisfaction when individuals' baseline satisfaction levels may differ.

A growing literature seeks to explain differences in individuals' self-reported satisfaction with their jobs. The evidence so far has mainly been based on cross-sectional data and when panel data have been used, individual unobserved heterogeneity has been modelled as an ordered probit model with random effects. This article makes use of longitudinal data for Denmark, taken from the waves 1995-1999 of the European Community Household Panel, and estimates fixed effects ordered logit models using the estimation methods proposed by Ferrer-i-Carbonel and Frijters (2004) and Das and van Soest (1999). For comparison and testing purposes a random effects ordered probit is also estimated. Estimations are carried out separately on the samples of men and women for individuals' overall satisfaction with the jobs they hold. We find that using the fixed effects approach (that clearly rejects the random effects specification), considerably reduces the number of key explanatory variables. The impact of central economic factors is the same as in previous studies, though. Moreover, the determinants of job satisfaction differ considerably between the genders, in particular once individual fixed effects are allowed for.

The consequences of substance use among gay and bisexual men : a consensual qualitative research analysis

- Background Substance use is common among gay/bisexual men and is associated with significant health risks (e.g. HIV transmission). The consequences of substance use, across the range of substances commonly used, have received little attention. The purpose of this study is to map participant’s beliefs about the effects of substance use to inform prevention, health promotion and clinical interventions. - Methods Participants were interviewed about experiences regarding their substance use and recruited through medical and sexual health clinics. Data were collected though a consumer panel and individual interviews. Responses regarding perceived consequences of substance use were coded using Consensual Qualitative Research (CQR) methodology. - Results Most participants reported lifetime use of alcohol, cannabis, stimulants and amyl nitrite, and recent alcohol and cannabis use. A wide range of themes were identified regarding participant’s thoughts, emotions and behaviours (including sexual behaviours) secondary to substance use, including: cognitive functioning, mood, social interaction, physical effects, sexual activity, sexual risk-taking, perception of sexual experience, arousal, sensation, relaxation, disinhibition, energy/activity level and numbing. Analyses indicated several consequences were consistent across substance types (e.g. cognitive impairment, enhanced mood), whereas others were highly specific to a given substance (e.g. heightened arousal post amyl nitrite use). - Conclusions Prevention and interventions need to consider the variety of effects of substance use in tailoring effective education programs to reduce harms. A diversity of consequences appear to have direct and indirect impacts on decision-making, sexual activity and risk-taking. Findings lend support for the role of specific beliefs (e.g. expectancies) related to substance use on risk-related cognitions, emotions and behaviours.

Deriving grassland management factors for a carbon accounting method developed by the intergovernmental panel on climate change

Grassland management affects soil organic carbon (SOC) storage and can be used to mitigate greenhouse gas emissions. However, for a country to assess emission reductions due to grassland management, there must be an inventory method for estimating the change in SOC storage. The Intergovernmental Panel on Climate Change (IPCC) has developed a simple carbon accounting approach for this purpose, and here we derive new grassland management factors that represent the effect of changing management on carbon storage for this method. Our literature search identified 49 studies dealing with effects of management practices that either degraded or improved conditions relative to nominally managed grasslands. On average, degradation reduced SOC storage to 95% +/- 0.06 and 97% +/- 0.05 of carbon stored under nominal conditions in temperate and tropical regions, respectively. In contrast, improving grasslands with a single management activity enhanced SOC storage by 14% 0.06 and 17% +/- 0.05 in temperate and tropical regions, respectively, and with an additional improvement(s), storage increased by another 11% +/- 0.04. We applied the newly derived factor coefficients to analyze C sequestration potential for managed grasslands in the U.S., and found that over a 20-year period changing management could sequester from 5 to 142 Tg C yr(-1) or 0.1 to 0.9 Mg C ha(-1) yr(-1), depending on the level of change. This analysis provides revised factor coefficients for the IPCC method that can be used to estimate impacts of management; it also provides a methodological framework for countries to derive factor coefficients specific to conditions in their region.

Psychometric analysis of the Brisbane Practice Environment Measure (B-PEM)

Purpose: To undertake rigorous psychometric testing of the newly developed contemporary work environment measure (the Brisbane Practice Environment Measure [B-PEM]) using exploratory factor analysis and confirmatory factor analysis. Methods: Content validity of the 33-item measure was established by a panel of experts. Initial testing involved 195 nursing staff using principal component factor analysis with varimax rotation (orthogonal) and Cronbach's alpha coefficients. Confirmatory factor analysis was conducted using data from a further 983 nursing staff. Results: Principal component factor analysis yielded a four-factor solution with eigenvalues greater than 1 that explained 52.53% of the variance. These factors were then verified using confirmatory factor analysis. Goodness-of-fit indices showed an acceptable fit overall with the full model, explaining 21% to 73% of the variance. Deletion of items took place throughout the evolution of the instrument, resulting in a 26-item, four-factor measure called the Brisbane Practice Environment Measure-Tested. Conclusions: The B-PEM has undergone rigorous psychometric testing, providing evidence of internal consistency and goodness-of-fit indices within acceptable ranges. The measure can be utilised as a subscale or total score reflective of a contemporary nursing work environment. Clinical Relevance: An up-to-date instrument to measure practice environment may be useful for nursing leaders to monitor the workplace and to assist in identifying areas for improvement, facilitating greater job satisfaction and retention.

Panel studies of new venture creation : a review and suggestions for future research

We review all journal articles based on “PSED-type” research, i.e., longitudinal, empirical studies of large probability samples of on-going, business start-up efforts. We conclude that the research stream has yielded interesting findings; sometimes by confirming prior research with a less bias-prone methodology and at other times by challenging whether prior conclusions are valid for the early stages of venture development. Most importantly, the research has addressed new, process-related research questions that prior research has shunned or been unable to study in a rigorous manner. The research has revealed an enormous and fascinating variability in new venture creation that also makes it challenging to arrive at broadly valid generalizations. An analysis of the findings across studies as well as an examination of those studies that have been relatively more successful at explaining outcomes give good guidance regarding what is required in order to achieve strong and credible results. We compile and present such advice to users of existing data sets and designers of new projects in the following areas: Statistically representative and/or theoretically relevant sampling; Level of analysis issues; Dealing with process heterogeneity; Dealing with other heterogeneity issues, and Choice and interpretation of dependent variables.

Marital loss, mental health and the role of perceived social support : findings from six waves of an Australian population based panel study

Objectives: To investigate the impact of transitions out of marriage (separation, widowhood) on the self reported mental health of men and women, and examine whether perceptions of social support play an intervening role. ---------- Methods: The analysis used six waves (2001–06) of an Australian population based panel study, with an analytical sample of 3017 men and 3225 women. Mental health was measured using the MHI-5 scale scored 0–100 (α=0.97), with a higher score indicating better mental health. Perceptions of social support were measured using a 10-item scale ranging from 10 to 70 (α=0.79), with a higher score indicating higher perceived social support. A linear mixed model for longitudinal data was used, with lags for marital status, mental health and social support. ---------- Results: After adjustment for social characteristics there was a decline in mental health for men who separated (−5.79 points) or widowed (−7.63 points), compared to men who remained married. Similar declines in mental health were found for women who separated (−6.65 points) or became widowed (−9.28 points). The inclusion of perceived social support in the models suggested a small mediation effect of social support for mental health with marital loss. Interactions between perceived social support and marital transitions showed a strong moderating effect for men who became widowed. No significant interactions were found for women. ---------- Conclusion: Marital loss significantly decreased mental health. Increasing, or maintaining, high levels of social support has the potential to improve widowed men's mental health immediately after the death of their spouse.

Reverse engineering and finite element analysis of a 3-wheeler automotive structure

Auto rickshaws (3-wheelers) are the most sought after transport among the urban and rural poor in India. The assembly of the vehicle involves assemblies of several major components. The L-angle is the component that connects the front panel with the vehicle floor. Current L-angle part has been observed to experience permanent deformation failure over period of time. This paper studies the effect of the addition of stiffeners on the L-angle to increase the strength of the component. A physical model of the L-angle was reversed engineered and modelled in CAD before static loading analysis were carried out on the model using finite element analysis. The modified L-angle fitted with stiffeners was shown to be able to withstand more load compare to previous design.

Panel studies of new venture creation: a methods-focused review and suggestions for future research

Longitudinal panel studies of large, random samples of business start-ups captured at the pre-operational stage allow researchers to address core issues for entrepreneurship research, namely, the processes of creation of new business ventures as well as their antecedents and outcomes. Here, we perform a methods-orientated review of all 83 journal articles that have used this type of data set, our purpose being to assist users of current data sets as well as designers of new projects in making the best use of this innovative research approach. Our review reveals a number of methods issues that are largely particular to this type of research. We conclude that amidst exemplary contributions, much of the reviewed research has not adequately managed these methods challenges, nor has it made use of the full potential of this new research approach. Specifically, we identify and suggest remedies for context-specific and interrelated methods challenges relating to sample definition, choice of level of analysis, operationalization and conceptualization, use of longitudinal data and dealing with various types of problematic heterogeneity. In addition, we note that future research can make further strides towards full utilization of the advantages of the research approach through better matching (from either direction) between theories and the phenomena captured in the data, and by addressing some under-explored research questions for which the approach may be particularly fruitful.

Soil carbon sequestration and associated economic costs for farming systems of the Indo-Gangetic Plain : a meta-analysis

Soil organic carbon sequestration rates over 20 years based on the Intergovernmental Panel for Climate Change (IPCC) methodology were combined with local economic data to determine the potential for soil C sequestration in wheat-based production systems on the Indo-Gangetic Plain (IGP). The C sequestration potential of rice–wheat systems of India on conversion to no-tillage is estimated to be 44.1 Mt C over 20 years. Implementing no-tillage practices in maize–wheat and cotton–wheat production systems would yield an additional 6.6 Mt C. This offset is equivalent to 9.6% of India's annual greenhouse gas emissions (519 Mt C) from all sectors (excluding land use change and forestry), or less than one percent per annum. The economic analysis was summarized as carbon supply curves expressing the total additional C accumulated over 20 year for a price per tonne of carbon sequestered ranging from zero to USD 200. At a carbon price of USD 25 Mg C−1, 3 Mt C (7% of the soil C sequestration potential) could be sequestered over 20 years through the implementation of no-till cropping practices in rice–wheat systems of the Indian States of the IGP, increasing to 7.3 Mt C (17% of the soil C sequestration potential) at USD 50 Mg C−1. Maximum levels of sequestration could be attained with carbon prices approaching USD 200 Mg C−1 for the States of Bihar and Punjab. At this carbon price, a total of 34.7 Mt C (79% of the estimated C sequestration potential) could be sequestered over 20 years across the rice–wheat region of India, with Uttar Pradesh contributing 13.9 Mt C.

Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island

Migraine is a common neurovascular disorder with a complex envirogenomic aetiology. In an effort to identify migraine susceptibility genes, we conducted a study of the isolated population of Norfolk Island, Australia. A large portion of the permanent inhabitants of Norfolk Island are descended from 18th Century English sailors involved in the infamous mutiny on the Bounty and their Polynesian consorts. In total, 600 subjects were recruited including a large pedigree of 377 individuals with lineage to the founders. All individuals were phenotyped for migraine using International Classification of Headache Disorders-II criterion. All subjects were genotyped for a genome-wide panel of microsatellite markers. Genotype and phenotype data for the pedigree were analysed using heritability and linkage methods implemented in the programme SOLAR. Follow-up association analysis was performed using the CLUMP programme. A total of 154 migraine cases (25%) were identified indicating the Norfolk Island population is high-risk for migraine. Heritability estimation of the 377-member pedigree indicated a significant genetic component for migraine (h2 = 0.53, P = 0.016). Linkage analysis showed peaks on chromosome 13q33.1 (P = 0.003) and chromosome 9q22.32 (P = 0.008). Association analysis of the key microsatellites in the remaining 223 unrelated Norfolk Island individuals showed evidence of association, which strengthen support for the linkage findings (P ≤ 0.05). In conclusion, a genome-wide linkage analysis and follow-up association analysis of migraine in the genetic isolate of Norfolk Island provided evidence for migraine susceptibility loci on chromosomes 9q22.22 and 13q33.1.

Computational analysis of laminated glass panels under blast loads: A comparison of two dimensional and three dimensional modelling approaches

This paper illustrates the use of finite element (FE) technique to investigate the behaviour of laminated glass (LG) panels under blast loads. Two and three dimensional (2D and 3D) modelling approaches available in LS-DYNA FE code to model LG panels are presented. Results from the FE analysis for mid-span deflection and principal stresses compared well with those from large deflection plate theory. The FE models are further validated using the results from a free field blast test on a LG panel. It is evident that both 2D and 3D LG models predict the experimental results with reasonable accuracy. The 3D LG models give slightly more accurate results but require considerably more computational time compared to the 2D LG models.

Failure analysis of laminated glass panels subjected to blast loads

This paper presents a rigorous and a reliable analytical procedure using finite element (FE) techniques to study the blast response of laminated glass (LG) panel and predict the failure of its components. The 1st principal stress (σ11) is used as the failure criterion for glass and the von mises stress (σv) is used for the interlayer and sealant joints. The results from the FE analysis for mid-span deflection, energy absorption and the stresses at critical locations of glass, interlayer and structural sealant are presented in the paper. These results compared well with those obtained from a free field blast test reported in the literature. The tensile strength (T) of the glass has a significant influence on the behaviour of the LG panel and should be treated carefully in the analysis. The glass panes absorb about 80% of the blast energy for the treated blast load and this should be minimised in the design.

Design, construction, and analysis of cell line arrays and tissue microarrays for gene expression analysis

Cell line array (CMA) and tissue microarray (TMA) technologies are high-throughput methods for analysing both the abundance and distribution of gene expression in a panel of cell lines or multiple tissue specimens in an efficient and cost-effective manner. The process is based on Kononen's method of extracting a cylindrical core of paraffin-embedded donor tissue and inserting it into a recipient paraffin block. Donor tissue from surgically resected paraffin-embedded tissue blocks, frozen needle biopsies or cell line pellets can all be arrayed in the recipient block. The representative area of interest is identified and circled on a haematoxylin and eosin (H&E)-stained section of the donor block. Using a predesigned map showing a precise spacing pattern, a high density array of up to 1,000 cores of cell pellets and/or donor tissue can be embedded into the recipient block using a tissue arrayer from Beecher Instruments. Depending on the depth of the cell line/tissue removed from the donor block 100-300 consecutive sections can be cut from each CMA/TMA block. Sections can be stained for in situ detection of protein, DNA or RNA targets using immunohistochemistry (IHC), fluorescent in situ hybridisation (FISH) or mRNA in situ hybridisation (RNA-ISH), respectively. This chapter provides detailed methods for CMA/TMA design, construction and analysis with in-depth notes on all technical aspects including tips to deal with common pitfalls the user may encounter. © Springer Science+Business Media, LLC 2011.