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Solitary pulmonary nodules (SPNs) measuring 8 to 30 mm in diameter require further workup to determine the likelihood of malignancy.What is the diagnostic performance of a lung cancer prediction convolutional neural network (LCP-CNN) in SPNs using unenhanced and contrast-enhanced CT imaging compared with the current clinical workup?This was a post hoc analysis of the Single Pulmonary Nodule Investigation: Accuracy and Cost-Effectiveness of Dynamic Contrast Enhanced Computed Tomography in the Characterisation of Solitary Pulmonary Nodules trial, a prospective multicenter study comparing the diagnostic accuracy of dynamic contrast-enhanced (DCE) CT imaging with PET imaging in SPNs. The LCP-CNN was designed and validated in an external cohort. LCP-CNN-generated risk scores were created from the noncontrast and contrast-enhanced CT scan images from the DCE CT imaging. The gold standard was histologic analysis or 2 years of follow-up. The area under the receiver operating characteristic curves (AUC) were calculated using LCP-CNN score, maximum standardized uptake value, and DCE CT scan maximum enhancement and were compared using the DeLong test.Two hundred seventy participants (mean ± SD age, 68.3 ± 8.8 years; 49% women) underwent PET with CT scan imaging and DCE CT imaging with CT scan data available centrally for LCP-CNN analysis. The accuracy of the LCP-CNN on the noncontrast images (AUC, 0.83; 95% CI, 0.79-0.88) was superior to that of DCE CT imaging (AUC, 0.76; 95% CI, 0.69-0.82; P = .03) and equal to that of PET with CT scan imaging (AUC, 0.86; 95% CI, 0.81-0.90; P = .35). The presence of contrast resulted in a small reduction in diagnostic accuracy, with the AUC falling from 0.83 (95% CI, 0.79-0.88) on the noncontrast images to 0.80 to 0.83 after contrast (P .05 for 240 s after contrast only).An LCP-CNN algorithm provides an AUC equivalent to PET with CT scan imaging in the diagnosis of solitary pulmonary nodules.ClinicalTrials.gov Identifier; No.: NCT02013063.

Association of frequency of marijuana use, duration of marijuana, and joint years of marijuana use with oropharyngeal and oral tongue cancers

Background: The incidence of oropharyngeal and oral tongue cancers has increased over the last 20 years which parallels increased use of marijuana among individuals born after 1950.Methods: A pooled analysis was conducted comprising individual-level data from nine case–control studies from the United States and Latin America in the INHANCE consortium. Self-reported information on marijuana smoking, demographic, and behavioral factors was obtained from 1,921 oropharyngeal cases, 356 oral tongue cases, and 7,639 controls.Results: Compared with never marijuana smokers, ever marijuana smokers had an elevated risk of oropharyngeal [adjusted OR (aOR), 1.24; 95% confidence interval (CI): 1.06–1.47] and a reduced risk of oral tongue cancer (aOR, 0.47; 95% CI, 0.29, 0.75). The risk of oropharyngeal cancer remained elevated among never tobacco and alcohol users. The risk of oral tongue cancer was reduced among never users of tobacco and alcohol. Sensitivity analysis adjusting for potential confounding by HPV exposure attenuated the association of marijuana use with oropharyngeal cancer (aOR, 0.99; 95% CI, 0.71–1.25), but had no effect on the oral tongue cancer association.Conclusions: These results suggest that the association of marijuana use with head and neck carcinoma may differ by tumor site.Impact: The associations of marijuana use with oropharyngeal and oral tongue cancer are consistent with both possible pro- and anticarcinogenic effects of cannabinoids. Additional work is needed to rule out various sources of bias, including residual confounding by HPV infection and misclassification of marijuana exposure. Cancer Epidemiol Biomarkers Prev; 23(1); 160–71. ©2013 AACR.

Description for sensitivity analysis to adjust for potential unmeasured confounding

Introduction: Current acute interventions for ischemic stroke aim to restore perfusion of affected tissue. There is an unmet need for therapies that protect neurons from ischemic damage and/or enhance natural repair processes to restore function. In humans, the neuronal growth and survival inhibitor RGMa (repulsive guidance molecule A) is upregulated following ischemic stroke. Elezanumab is a novel, humanized monoclonal antibody targeting RGMa. Preclinical evidence in traumatic and ischemic models of CNS damage suggest a protective and regenerative mechanisms for elezanumab following CNS damage. Methods: Elezanumab was evaluated in a rabbit permanent middle cerebral artery occlusion (MCAO) model of acute ischemic stroke by injection of an autologous blood clot. In replicate experiments, elezanumab (1, 10 and 40 mg/kg) or IgG control was administered 6 hours post occlusion or 24 hours post occlusion (10 mg/kg). Animals were dosed weekly through 28 days. Functional ability was assessed using the Neuromotor Score, a composite of sensorimotor performance tasks. Ex vivo MRI, histology, and fluid biomarker analyses were performed. Results: MCAO consistently reduced cerebral blood flow by ~60% and resulted in neuromotor dysfunction. All doses of elezanumab demonstrated statistically significantly improved neuromotor function and recovery rate versus controls when dosed 6 hours post occlusion. The 10 mg/kg group dosed 24 hours post occlusion did not show a statistically significant functional improvement versus controls. Infarct volumes, plasma neurofilament light chain levels, and histological evidence of microglial proliferation were all significantly reduced with elezanumab treatment versus controls, including in the delayed elezanumab treatment group. Conclusions: Elezanumab treatment was associated with improved functional recovery and reduced markers of neuronal damage. Collectively, these data support a neuroprotective role for elezanumab in this translational model of acute ischemic stroke. Elezanumab is now being tested in a Phase 2a clinical trial for acute ischemic stroke.

The ability to think creatively is a vital transition skill for students with learning disabilities in the 21st century. Participation in careers with a high level of creative thinking ability not only sets the individual student up for success but also the community in which they live. Creative self-efficacy is the belief in one’s ability to be creative and is a basic component of creativity. A positive relationship is indicated between higher creative self-efficacy and higher creative production. Thus, the development of a positive creative self serves as a supportive element for students with learning disabilities in their current and future endeavors. This article describes the importance of and need for creative thinking and creative self-efficacy development in education and suggests the use of questioning techniques as a strategy for developing these important skills when working with students with learning disabilities.

IntroductionLow-dose CT (LDCT) screening of high-risk smokers reduces lung cancer (LC) specific mortality. Determining screening eligibility using individualised risk may improve screening effectiveness and reduce harm. Here, we compare the performance of two risk prediction models (PLCOM2012 and Liverpool Lung Project model (LLPv2)) and National Lung Screening Trial (NLST) eligibility criteria in a community-based screening programme.MethodsEver-smokers aged 55–74, from deprived areas of Manchester, were invited to a Lung Health Check (LHC). Individuals at higher risk (PLCOM2012 score ≥1.51%) were offered annual LDCT screening over two rounds. LLPv2 score was calculated but not used for screening selection; ≥2.5% and ≥5% thresholds were used for analysis.ResultsPLCOM2012 ≥1.51% selected 56% (n=1429) of LHC attendees for screening. LLPv2 ≥2.5% also selected 56% (n=1430) whereas NLST (47%, n=1188) and LLPv2 ≥5% (33%, n=826) selected fewer. Over two screening rounds 62 individuals were diagnosed with LC; representing 87% (n=62/71) of 6-year incidence predicted by mean PLCOM2012 score (5.0%). 26% (n=16/62) of individuals with LC were not eligible for screening using LLPv2 ≥5%, 18% (n=11/62) with NLST criteria and 7% (n=5/62) with LLPv2 ≥2.5%. NLST eligible Manchester attendees had 2.5 times the LC detection rate than NLST participants after two annual screens (≈4.3% (n=51/1188) vs 1.7% (n=438/26 309); padjOR 2.50, 95% CI 1.11 to 5.64; p=0.028).ConclusionProspective comparisons of risk prediction tools are required to optimise screening selection in different settings. The PLCOM2012 model may underestimate risk in deprived UK populations; further research focused on model calibration is required.

BackgroundCOPD is a major cause of morbidity and mortality in populations eligible for lung cancer screening. We investigated the role of spirometry in a community-based lung cancer screening programme.MethodsEver smokers, age 55–74, resident in three deprived areas of Manchester were invited to a ‘Lung Health Check’ (LHC) based in convenient community locations. Spirometry was incorporated into the LHCs alongside lung cancer risk estimation (Prostate, Lung, Colorectal and Ovarian Study Risk Prediction Model, 2012 version (PLCOM2012)), symptom assessment and smoking cessation advice. Those at high risk of lung cancer (PLCOM2012 ≥1.51%) were eligible for annual low-dose CT screening over two screening rounds. Airflow obstruction was defined as FEV1/FVCResults99.4% (n=2525) of LHC attendees successfully performed spirometry; mean age was 64.1±5.5, 51% were women, 35% were current smokers. 37.4% (n=944) had airflow obstruction of which 49.7% (n=469) had no previous diagnosis of COPD. 53.3% of those without a prior diagnosis were symptomatic (n=250/469). After multivariate analysis, the detection of airflow obstruction without a prior COPD diagnosis was associated with male sex (adjOR 1.84, 95% CI 1.37 to 2.47; p1/FVC ratio (adjOR 4.19, 95% CI 2.95 to 5.95; padjOR 2.80, 95% CI 1.60 to 8.42; p=0.002).ConclusionsIncorporating spirometry into a community-based targeted lung cancer screening programme is feasible and identifies a significant number of individuals with airflow obstruction who do not have a prior diagnosis of COPD.

Objective:\ud We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries.\ud \ud Subjects and Methods:\ud The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared.\ud \ud Results:\ud The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (

Introduction: Treatment of acute ischemic stroke focuses on reperfusion but is limited by timing and other exclusions, and despite intervention, patients may sustain residual neurologic impairment. In addition to initial excitotoxic reactions following occlusion, upregulation of factors such as repulsive guidance molecule A (RGMa) inhibits cell survival and neuronal repair in infarcted regions. In vivo neutralization of RGMa is associated with decreased lesion size, reduced glial scarring, and enhanced functional recovery in animal models of cerebral artery occlusion; thus, RGMa suppression represents a novel therapeutic target due to its potential protective and restorative mechanisms. Elezanumab is an investigational monoclonal antibody that binds specifically to RGMa and is being evaluated for its function after ischemic stroke. Methods: Elezanumab in Acute Ischemic Stroke (EAISE) is a 52-week, phase 2a, randomized, double-blind, placebo-controlled study evaluating safety, efficacy, and pharmacokinetics of elezanumab in patients with acute ischemic stroke (NCT04309474). Patients will be randomized 1:1 within 23 hours since “last known normal” to receive elezanumab or placebo and every 4 weeks thereafter through week 48. Patients must be aged 30-90 years with a clinical diagnosis of acute ischemic stroke in anterior circulation and have a National Institutes of Health Stroke Scale (NIHSS) total score of 7 to 21. Patients who receive tissue plasminogen activator or endovascular therapy will be eligible if they continue to exhibit an NIHSS of 7 to 21 after treatment. Patients with evidence of seizure on stroke onset and history of repeated episodes of complex migraines will be excluded. Results: Projected enrollment is 120 patients across 45 sites in multiple countries. Primary endpoint is the NIHSS total score throughout the treatment period. Secondary endpoint is a favorable outcome based on the modified Rankin Scale, defined as a score of 0-2 at week 52. Exploratory outcomes include activities of daily living, cognition, mood, and fluid and imaging biomarkers. Conclusion: This phase 2 study will evaluate safety and efficacy of elezanumab, a novel therapeutic intervention to improve neurological recovery after acute ischemic stroke.

York International York University International Association of Universities (IAU) Canadian Commission for UNESCO (CCU) Okayama University (Japan)

Dr. Erica McCray is professor and associate dean for Faculty Affairs, Diversity, Equity, Inclusion, and Community Engagement in the College of Education at the University of Florida. In addition, she serves as co-principal investigator of the CEEDAR Center, an Office of Special Education Programs technical assistance project, and a National Science Foundation research project to broaden participation in engineering. Dr. McCray shares her non-linear path to higher education, which is driven by her strong desire to make the world a better place, particularly for those with disabilities and those from marginalized groups.

Low-dose CT (LDCT) screening of high-risk smokers reduces lung cancer (LC) specific mortality. Determining screening eligibility using individualised risk may improve screening effectiveness and reduce harm. Here, we compare the performance of two risk prediction models (PLCOEver-smokers aged 55-74, from deprived areas of Manchester, were invited to a Lung Health Check (LHC). Individuals at higher risk (PLCOPLCOProspective comparisons of risk prediction tools are required to optimise screening selection in different settings. The PLCO

Exosomes carry microRNA biomarkers, occur in higher abundance in cancerous patients than in healthy ones, and because they are present in most biofluids, including blood and urine, these can be obtained noninvasively. Standard laboratory techniques to isolate exosomes are expensive, time consuming, provide poor purity, and recover on the order of 25% of the available exosomes. We present a new microfluidic technique to simultaneously isolate exosomes and preconcentrate them by electrophoresis using a high transverse local electric field generated by ion-depleting ion-selective membrane. We use pressure-driven flow to deliver an exosome sample to a microfluidic chip such that the transverse electric field forces them out of the cross flow and into an agarose gel which filters out unwanted cellular debris while the ion-selective membrane concentrates the exosomes through an enrichment effect. We efficiently isolated exosomes from 1× PBS buffer, cell culture media, and blood serum. Using flow rates from 150 to 200 μL/h and field strengths of 100 V/cm, we consistently captured between 60 and 80% of exosomes from buffer, cell culture media, and blood serum as confirmed by both fluorescence spectroscopy and nanoparticle tracking analysis. Our microfluidic chip maintained this recovery rate for more than 20 min with a concentration factor of 15 for 10 min of isolation.

Amidation of indole 2-carboxylate 1 with ammonia gas via the imidazolide 2 gave GSK2248761A API 3, which was in development for the treatment of HIV. Three significant impurities, namely the phosphinic acid 4, the N-acyl urea 8, and the indoloyl carboxamide 6, were formed during the reaction, and the original process was unable to produce API within clinical specification when run at scale. Investigation into the origin, fate, and control of these impurities led to a new process which was able to produce API within clinical specification.

Despite an increase of access for Students of Color in higher education in the United States over the past 20 years, institutions continue to fail Black student populations as evidenced by sustained low graduation rates. This chapter examines ten institutions recognized by Harper and Simmons as being among the institutions that graduate a higher percentage of Black students when compared to their majority counterparts. Additional data were gathered via institutional websites, public reports, and interviews with administrators at various campuses. Graduation rates for Black students, institutional type, student affairs and academic programs, and campus-wide initiatives are discussed within each institution. An institutional understanding of barriers to graduating Students of Color was a key factor in Black student success, followed by responding to those barriers through institutional collaboration and programming, and an institutional appreciation of diversity, equity, and inclusion were also found to be common practices among each of these highlighted institutions.

We report results from the second annual screening round (T1) of Manchester’s ‘Lung Health Check’ pilot of community-based lung cancer screening in deprived areas (undertaken June to August 2017). Screening adherence was 90% (n=1194/1323): 92% of CT scans were classified negative, 6% indeterminate and 2.5% positive; there were no interval cancers. Lung cancer incidence was 1.6% (n=19), 79% stage I, treatments included surgery (42%, n=9), stereotactic ablative radiotherapy (26%, n=5) and radical radiotherapy (5%, n=1). False-positive rate was 34.5% (n=10/29), representing 0.8% of T1 participants (n=10/1194). Targeted community-based lung cancer screening promotes high screening adherence and detects high rates of early stage lung cancer.

The mutagenic-impurity control strategy for a second generation manufacturing route to the non-mutagenic antipneumocystic agent atovaquone (2-((1R,4R)-4-(4-chlorophenyl)cyclohexyl)-3-hydroxynaphthalene-1,4-dione) 1 is described. Preliminary assessment highlighted multiple materials of concern which were largely discharged either through returning a negative bacterial mutagenicity assay or through confidence that the impurity would be purged during the downstream processing from when it was first introduced. Additional genotoxicity testing highlighted two materials of concern where initial assessment suggested that testing for these impurities at trace levels within the drug substance would be required. Following a thorough review of process purging detail, spiking and purging experimentation, and an understanding of the process parameters to which they were exposed an ICH M7 Option 4 approach could be justified for their control. The development of two 1H NMR spectroscopy methods for measurement of these impurities is also described as well as a proposed summary table for describing the underlying rationale for ICH M7 control rationales to regulators. This manuscript demonstrates that process purging of potential mutagenic impurities can be realised even when they are introduced in the later stages of a process and highlights the importance of scientific understanding rather than relying on a stage-counting approach.

Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in populations eligible for lung cancer screening. The aim of this study was to determine whether a brief CV risk assessment, delivered as part of a targeted community-based lung cancer screening programme, was effective in identifying individuals at high risk who might benefit from primary prevention. Methods: The Manchester Lung Screening Pilot consisted of annual low dose CT (LDCT) over 2 screening rounds, targeted at individuals in deprived areas at high risk of lung cancer (age 55–74 and 6-year risk ≥1.51%, using PLCOM2012 risk model). All participants of the second screening round were eligible to take part in the study. Ten-year CV risk was estimated using QRISK2 in participants without CVD and compared to age (±5 years) and sex matched Health Survey for England (HSE) controls; high risk was defined as QRISK2 score ≥10%. Coronary artery calcification (CAC) was assessed on LDCT scans and compared to QRISK2 score. Results: Seventy-seven percent (n=920/1,194) of screening attendees were included in the analysis; mean age 65.6 ± 5.4 and 50.4% female. QRISK2 and lung cancer risk (PLCOM2012) scores were correlated (r = 0.26, p < 0.001). Median QRISK2 score was 21.1% (IQR 14.9–29.6) in those without established CVD (77.6%, n = 714/920), double that of HSE controls (10.3%, IQR 6.6–16.2; n = 714) (p < 0.001). QRISK2 score was significantly higher in those with CAC (p < 0.001). Screening attendees were 10-fold more likely to be classified high risk (OR 10.2 [95% CI 7.3–14.0]). One third (33.7%, n = 310/920) of all study participants were high risk but not receiving statin therapy for primary CVD prevention. Discussion: Opportunistic CVD risk assessment within a targeted lung cancer screening programme is feasible and is likely to identify a very large number of individuals suitable for primary prevention.

Aim: To study early changes in fatigue, disease activity and cytokines within individual patients with rheumatoid arthritis (RA) following etanercept treatment. Methods: 12-week prospective observational study of 21 RA patients starting etanercept therapy. DAS28, fatigue, IL-1β, IL-4, IL-6, IL-8 and IL-1ra were measured. Results: DAS28, fatigue and IL-6 improved significantly by 40% compared with baseline values in the first 4 weeks (P < 0.05), but followed different time courses. The main improvement in IL-6 occurred by week 2, fatigue (BRAF MDQ) by week 3 and DAS28 by week 4. At week 3 improvement of DAS28 (24%) was significantly less than BRAF MDQ (42%, P < 0.003) and IL-6 (43%, P < 0.03). Conclusion: Fatigue improved faster than disease activity, suggesting that fatigue may be mediated via a different pathway.

We report baseline results of a community-based, targeted, low-dose CT (LDCT) lung cancer screening pilot in deprived areas of Manchester. Ever smokers, aged 55–74 years, were invited to ‘lung health checks’ (LHCs) next to local shopping centres, with immediate access to LDCT for those at high risk (6-year risk ≥1.51%, PLCOM2012 calculator). 75% of attendees (n=1893/2541) were ranked in the lowest deprivation quintile; 56% were high risk and of 1384 individuals screened, 3% (95% CI 2.3% to 4.1%) had lung cancer (80% early stage) of whom 65% had surgical resection. Taking lung cancer screening into communities, with an LHC approach, is effective and engages populations in deprived areas.

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. VIDEO ABSTRACT.

Selectivity against mutant nontargets with a few mismatches remains challenging in nucleic acid sensing. Sensitivity enhancement by analyte concentration does not improve selectivity because it affects targets and nontargets equally. Hydrodynamic or electrical shear enhanced selectivity is often accompanied by substantial losses in target signals, thereby leading to poor limits of detection. We introduce a platform based on depletion isotachophoresis in agarose gel generated by an ion-selective membrane that allows both selectivity and sensitivity enhancement with a two-step assay involving concentration polarization at an ion-selective membrane. By concentrating both the targets and probe-functionalized nanoparticles by ion enrichment at the membrane, the effective thermodynamic dissociation constant is lowered from 40 nM to below 500 pM, and the detection limit is 10 pM as reported previously. A dynamically optimized ion depletion front is then generated from the membrane with a high electrical shear force to selectively and irreversibly dehybridize nontargets. The optimized selectivity against a two-mismatch nontarget (in a 35-base pairing sequence) is shown to be better than the thermodynamic equilibrium selectivity by more than a hundred-fold, such that there is no detectable signal from the two-mismatch nontarget. We offer empirical evidence that irreversible cooperative dehybridization plays an important role in this kinetic selectivity enhancement and that mismatch location controls the optimum selectivity even when there is little change in the corresponding thermodynamic dissociation constant.

Herein is reported the separation and identification of a previously unknown imidazoline by-product originating from the fluorescent labeling procedure when applied to enzymatically released N-linked glycans of a human IgG1. The imidazoline by-product was generated via the reductive amination procedure with either sodium cyanoborohydride or 2-picoline borane. Using ultra performance liquid chromatography (UPLC) in conjunction with hydrophilic interaction-based chromatography (HILIC), the 2-aminobenzoic acid (2-AA)-labeled glycans were well-resolved from imidazoline by-products to facilitate direct identification utilizing electrospray ionization mass spectrometry (ESI–MS) with fragmentation. It was found that this minor species (∼2%) was 18.0105 u less than the neighboring peak GlcNAc 2 Man 3 GlcNAc 2 Fuc peak, abbreviated as A2G0F at 1582.5899 u. While this mass loss corresponds to the mass of a water molecule, the molecular location of loss of water was not straightforward in consideration of the biantennary A2G0F structure. Model studies were carried out using A2G0F standard and N- acetyllactosamine to identify the impurity as an imidazoline ring structure located at the reducing end of the glycan as confirmed by high resolution mass fragment ions. Imidazoline content decreased when the reductant concentration was increased. To conclude, evidence for the imidazoline structure was accomplished through high resolution, high accuracy mass spectrometry (HRAM), and experiments showing chemical susceptibility and isotopically labeled tracers. This study is the first to identify these minor species which likely impact all N -acetylglucosamine-type N-linked glycans from biologics.

Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.

Stress interactions and sliding characteristics of faults with random fractal waviness in a purely elastic medium differ both qualitatively and quantitatively from those of faults with planar surfaces. With nonplanar fault models, solutions for slip diverge as resolution of the fractal features increases, and the scaling of fault slip with fault rupture dimension becomes nonlinear. We show that the nonlinear scaling of slip and divergence of solutions arise because stresses from geometric interactions at irregularities along nonplanar faults grow with increasing slip and produce backstresses that progressively impede slip. However, in real materials with finite strength, yielding will halt the growth of the interaction stresses, which will profoundly affect slip of nonplanar faults. We infer that in the brittle seismogenic portion of the Earth’s crust, off-fault yielding occurs on pervasive secondary faults. Predicted rates of stress relaxation with distance from major faults with random fractal roughness follow a power-law relationship that is consistent with reported clustering of background seismicity up to 15 kilometers from faults.

This article presents an innovative model of Continuing Professional Development (CPD) that has been used in Scotland to encourage research and to develop research skills amongst applied educational (school) psychologists. 1 This is a process-based CPD model rather than the traditional `attendance at CPD workshops' model, leading to active learning and knowledge creation for the professional and the profession. Data collected from educational psychologists and stakeholders suggests that it is very effective but there is room for improvement. The lessons learnt over the 13 years of its operation and through a recently commissioned evaluation will hopefully be of interest to other applied educational psychologists internationally, as well as related professions.

Our poster will describe how Building Healthier and Happier Communities – a national programme, delivered locally – will demonstrate the difference an investment in community capacity makes to managing demand on primary care services. Charities, community groups, social enterprises and voluntary organisations of all shapes and sizes already make significant impacts in areas like early intervention, prevention and care and support for people with complex and multiple conditions but there is scope for them to do more. By shifting resources to build organisations’ capacity, extend their reach and improve their connections, we aim to ensure that more people get the help and support they need without having to visit their GP or other health and social care services. In addition, our programme engages with public sector colleagues to improve their understanding of how the third sector works with people to improve their health and happiness and how, by equipping people to do more for themselves and each other, third sector organisations play an important and ongoing role in building community resilience. Our poster will outline the Scottish commitment to health and social care integration, prevention and co-production; explain how our programme contributes to that change agenda; present our theory of change in the form of a logic model; set out in graphic form the process we have developed for delivering the investment (both direct funding and other forms of support); illustrate our cross-sector partnership approach; and depict the projects which have been selected to receive that support. It will also share some of the key learning points from the project so far.

Problem-based learning (PBL) is an approach to teaching and learning that integrates learning using complex problems as the core curriculum. Other core features are its utilisation of small group and independent learning, and a focus on the development of life-long learning skills. A PBL approach was incorporated into the two-year postgraduate professional training programme for Educational Psychologists in cohort 2002–04.This paper presents initial results of a longitudinal evaluation of Educational Psychologists in Training’s (EPiTs) perceptions and experiences of PBL on the MSc training programme at Dundee University. Twenty-three EPiTs completed an anonymous questionnaire on PBL. There were three main areas of focus: the contribution of PBL to their level of preparedness for their future role as Educational Psychologists; the perceived strengths and weaknesses of the PBL approach; and their experiences of small group learning. The results are discussed in relation to changes made to the programme.

Background The influence of grief and bereavement on the lives of people with intellectual disabilities is currently receiving much interest. Many of the long-standing rituals associated with bereavement are still practised in Ireland, probably more than in many other Western countries. The present authors were interested in studying the experience of bereavement for people with intellectual disabilities in Ireland, and in making international comparisons. Method This mixed method study was carried out using two questionnaires. The first was used to study national service and organisational approaches to bereavement. The second questionnaire (based on Murray et al. 2000) was used to study a staff group working in Ireland, assessing staff knowledge and understanding of the grieving process. The results were compared with a UK staff group who were assessed using the same questionnaire (Murray et al. 2000). Results Staff and service attitudes were found to be very positive in supporting people with intellectual disabilities who have been bereaved. There is considerable understanding of the needs of bereaved individuals, and there is a high level of support in the participation in grief rituals. When compared with a UK staff group, Irish staffs were more inclined to encourage individuals to take part in bereavement rituals, though they had less actual experience in supporting bereaved people. Only one service had written bereavement guidelines. Conclusions There appears to be cultural differences in the experience of bereavement for people with intellectual disabilities. This is important in the context of staff training and policy development in grief and bereavement.

Background: Detection of urothelial carcinoma (UC) by urine cytology can be challenging. Recently, ProEx C has been studied as a marker to improve detection of UC. ProEx C is an assay targeting expression of topoisomerase IIa and minichromosome maintenance protein-2 and is currently utilized to assist in diagnoses of the gynecological specimens. In this study, we compared the utility of ProEx C and UroVysion in urine specimens. Materials and Methods: Twenty-seven urine specimens with UroVysion assay analysis and surgical biopsy follow-up were selected. The smears were stained with ProEx C. ProEx C and UroVysion assay results were separated into two categories based on surgical biopsy follow-up (benign or neoplastic). Surgical biopsy diagnoses were used as the gold standard for comparative evaluation of the two assays. The surgical follow-up was 9 benign, 2 low grade, and 16 high grade UCs. Results: The sensitivity was 88.9% for ProEx C and 55.6% for UroVysion, while the specificity was 77.8% for ProEx C and 44.4% for UroVysion. Positive predictive value was 88.9% for ProEx C and 66.7% for UroVysion. Negative predictive value was 77.8% and 33.3% for ProEx C and UroVysion, respectively. Using the two-tailed paired t-test, P value of 0.033 was obtained when ProEx C stain was compared with the UroVysion assay. Conclusion: ProEx C immunocytochemistry has a more favorable performance than fluorescent in-situ hybridization with a significant difference between the two assays using paired two-tail t-test (P = 0.0033).