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Mouse B cells are used in workflows to discover novel therapeutic antibodies or develop preclinical applications using genetically engineered B cells. In vitro expansion of B cells offers the opportunity to improve the recovery of antibody sequences and aids in the potential increase in the diversity of the B cell repertoire. Achieving robust expansion of B cells in culture can be challenging, as it typically requires the addition of serum, feeder cells, or specialized culture plates. The addition of serum can introduce unknown factors and result in lot-to-lot variability. Therefore, we have developed a first-to-market culture system that does not require the use of serum, feeder cells, or specialized culture plates to achieve robust in vitro expansion of mouse pan-B cells. Pan-B cells isolated from mouse splenocytes by immunomagnetic enrichment were cultured in serum-free ImmunoCultTM-XF B Cell Base Medium supplemented with ImmunoCultTM-ACF Mouse B Cell Expansion Supplement for > 9 days, starting with seeding densities of 100,000 cells/well and passaging every 3 days. Although pronounced donor variability was observed in the rate of expansion of viable cells, mean ~13-fold, ~150-fold, and ~200-fold rates were observed after 3, 6, and 9 days in culture, respectively (n=6 donors; range 94- to 328-fold at day 9). The expanded B cells also upregulated expression of activation and differentiation markers such as CD86 (mean 74%; n=6 donors; range 34 – 90%), CD138 (mean 68%; n=6 donors; range 57 – 73%), and CD267 (mean 79%; n=6 donors; range 49 – 91%) at day 9. The expansion supplement should facilitate mouse B cell studies for antibody discovery and diverse basic and translational applications.

Purpose - The purpose of the study is to examine the relationships among the following retail operations variables: retail store operations (i.e.,...

We report a cohort study of survival of patients with lung cancer presenting to a single multidisciplinary team between 1997 and 2011, according to symptoms at presentation. The overall median survival of the 3800 lung cases was 183 days (95% CI 171 to 195). There was a statistically significant difference in survival between the 12 symptom groups identified both without and with adjustment for the prognostic variables of age, gender and histology (P

Portfolio companies with cross-cultural venture-backing that produce patents which are textually more similar to industry peers also produce more patents and higher quality patents. 4.9 million cosine similarity measures between the patents of 958 venture-backed portfolio companies from 28 different nations provide results that are able to generalize beyond the English language with the addition of a cultural-linguistic distance measure. Latent Dirichlet allocation topic modeling applied to the patent text validates these categories, making these results robust against deviation between industries. The results provide a textual measure that venture capital firms from all nations can use to determine if the patents produced by their portfolio companies are the type that encourage greater innovation.

Background: The ELCID (Early Lung Cancer Investigation and Diagnosis) trial was a feasibility randomised controlled trial examining the effect on lung cancer diagnosis of lowering the threshold for referral for urgent chest x-ray for smokers and recent ex-smokers, aged over 60 years with new chest symptoms. The qualitative component aimed to explore the feasibility of individually randomising patients to an urgent chest x-ray or not and to investigate any barriers to patient recruitment and participation. We integrated this within the feasibility trial to inform the design of any future definitive trial, particularly in view of the lack of research exploring symptomatic patients’ experiences of participating in diagnostic trials for possible/suspected lung cancer. Although previous studies contributed valuable information concerning screening for lung cancer and patient participation in trials, this paper is the first to explore issues relating to this specific patient group.\ud \ud \ud \ud Methods: Qualitative interviews were conducted with 21 patients, comprising 9 who had been randomised to receive an immediate chest x-ray, 10 who were randomised to receive the standard treatment according to the National Institute for Health and Care Excellence guidelines, and 2 who chose not to participate in the trial. Interviews were analysed using a framework approach.\ud \ud \ud \ud Results: The findings of this analysis showed that altruism, personal benefit and the reassurance of not having lung cancer were important factors in patient participation. However, patients largely believed that being in the intervention arm was more beneficial, highlighting a lack of understanding of clinical equipoise. Disincentives to participation in the trial included the stigmatisation of patients who smoked (given the inclusion criteria). Although the majority of patients reported that they were happy with the trial design, there was evidence of poor understanding. Last, for several patients, placing trust in health professionals was preferred to understanding the trial processes.\ud \ud \ud \ud Conclusions: The integration of a qualitative study focusing on participant experience as a secondary outcome of a feasibility trial enabled exploration of patient response to participation and recruitment. The study demonstrated that although it is feasible to recruit patients to the ELCID trial, more work needs to be done to ensure an understanding of study principles and also of smoking stigmatisation.\ud \ud \ud \ud Trial registration: ClinicalTrials.gov, NCT01344005. Registered on 27 April 2011.

BACKGROUND: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. METHODS: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. RESULTS: The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. CONCLUSIONS: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care.British Journal of Cancer advance online publication 10 January 2017; doi:10.1038/bjc.2016.414 www.bjcancer.com.

Background: Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on\ud Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the\ud early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional\ud and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis.\ud Methods: A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model\ud calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early\ud awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years\ud (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the ‘worried-well’\ud population and the route of diagnosis that might occur as a result of the campaigns.\ud Results: The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY\ud gains of 289 and 178 QALYs and ICERs of d13 660 and d18 173 per QALY gained, respectively. The scenarios found that increases\ud in the ‘worried-well’ population may impact the cost-effectiveness conclusions.\ud Conclusions: Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the\ud potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study.\ud In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease\ud progression in the undiagnosed population.

Background Poor UK lung cancer survival rates may, in part, be due to late diagnosis. Objectives To evaluate the effectiveness of a mixedmethod community-based social marketing intervention on lung cancer diagnoses. Methods A public awareness campaign in conjunction with brief intervention training in general practices was piloted in six localities with a high lung cancer incidence. End points were self-reported awareness of lung cancer symptoms; intention to seek healthcare; chest x-ray referral rates in primary care; secular trends in the incidence of lung cancer and stage at diagnosis, compared before and after the intervention. Results 21% (128/600) (95% CI 18% to 25%) of the targeted population recalled something about the campaign. Compared with a responder in the control area, the odds of a responder in the intervention area saying that they would visit their general practitioner and request a chest x-ray for a cough was 1.97 times (95% CI 1.18 to 3.31, p¼0.01). Primary care chest x-ray referral rates increased by 20% in the targeted practices in the year following the intervention compared with a 2% fall in the control practices. The difference was highly significant, with an incidence rate ratio of 1.22 (95% CI 1.12 to 1.33, p¼0.001). There was a 27% increase in lung cancer diagnoses in the intervention area compared with a fall in the control area. The incidence rate ratio was 1.42 (95% CI 0.83 to 2.44 p¼0.199). Conclusion This is encouraging early evidence that an awareness and early recognition initiative may facilitate lung cancer diagnosis.

Finding an abnormality on a plain chest radiograph is usually the first definite evidence of a lung cancer, so this investigation is currently pivotal in the diagnosis of the disease. Although the National Institute for Clinical Excellence (NICE) has produced guidance on when a chest radiograph should be done for putative lung cancer presentations, cancer will usually be only one of a number of possible diagnoses, so this is somewhat artificial. Neither is there any evidence that obtaining a chest radiograph for these features leads to an improved outcome. Another major concern is the poor public awareness of the symptoms for which a chest radiograph is recommended. This article discusses the role of the chest radiograph in the early diagnosis of lung cancer with particular emphasis on the limited value of a single negative result and on the potential implications of interventions to increase the number of chest radiographs done in primary care.

AIMS: To assess the route to secondary care for patients with possible occupational asthma, and to document the duration of work-related symptoms and referral times. METHODS: Consecutive patients with suspected occupational asthma were recruited to a case series from six secondary care clinics with an interest in occupational asthma. Semi-structured interviews were performed and hospital case notes were reviewed to summarise relevant investigations and diagnosis. RESULTS: 97 patients were recruited, with a mean age of 44.2 years (range 24–64), 51 of whom (53%) had occupational asthma confirmed as a diagnosis. Most (96%) had consulted their general practitioner (GP) at least once with work-related respiratory symptoms, although these had been present for a mean of 44.6 months (range 0–320 months) on presentation to secondary care. Patients experienced a mean delay for assessment in secondary care of 4 years (range 1–27 years) following presentation in primary care. CONCLUSIONS: Significant diagnostic delay currently occurs for patients with occupational asthma in the UK.

Background In order to improve lung cancer survival in the UK, a greater proportion of resectable cancers must be diagnosed. It is likely that resectability rates would be increased by more timely diagnosis. Aside from screening, the only way of achieving this is to reduce the time to diagnosis in symptomatic cancers. Currently, lung cancers are mainly diagnosed by general practitioners (GPs) using the National Institute for Health and Clinical Excellence (NICE) guidelines for urgent referral for chest X-ray, which recommend urgent imaging or referral for patients who have one of a number of chest symptoms for more than 3 weeks. We are proposing to expand this recommendation to include one of a number of chest symptoms of any duration in higher-risk patients. Methods/Design We intend to conduct a trial of imaging in these higher-risk patients and compare it with NICE guidelines to see if imaging improves stage at diagnosis and resection rates. This trial would have to be large (and consequently resource-intensive) because most of these patients will not have lung cancer, making optimal design crucial. We are therefore conducting a pilot trial that will ascertain the feasibility of running a full trial and provide key information that will be required in order to design the full trial. Discussion This trial will assess the feasibility and inform the design of a large, UK-wide, clinical trial of a change to the NICE guidelines for urgent referral for chest X-ray for suspected lung cancer. It utilizes a combination of workshop, health economic, quality of life, qualitative, and quantitative methods in order to fully assess feasibility. Trial registration Clinicaltrials.gov NCT01344005

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To investigate the levels of agreement between expert respiratory physicians when making a diagnosis of occupational asthma.19 cases of possible occupational asthma were identified as part of a larger national observational cohort. A case summary for each case was then circulated to 12 physicians, asking for a percentage likelihood, from the supplied information, that this case represented occupational asthma. The resulting probabilities were then compared between physicians using Spearman's rank correlation and Cohen's kappa coefficients.Agreement between the 12 physicians for all 19 cases was generally good as assessed by Spearman's rank correlation. For all 66 physician-physician interactions, 45 were found to correlate significantly at the 5% level. The agreement assessed by kappa analysis was more variable, with a median kappa value of 0.26, (range -0.2 to +0.76), although 7 of the physicians agreed significantly (p0.05) withor=5 of their colleagues. Only in one case did the responses for probability of occupational asthma all exceed the "on balance" 50% threshold, although 12 of the 19 cases had an interquartile range of probabilities not including 50%, implying "on balance" agreement. The median probability values for each physician (all assessing the identical 19 cases) varied from 20% to 70%. Factors associated with a high probability rating were the presence of a positive serial peak expiratory flow Occupation Asthma SYStem (OASYS)-2 chart, and both the presence of bronchial hyper-reactivity and significant change in reactivity between periods of work and rest.Despite the importance of the diagnosis of occupational asthma and reasonable physician agreement, certain variations in diagnostic assessment were seen between UK expert centres when assessing paper cases of possible occupational asthma. Although this may in part reflect the absence of a normal clinical consultation, a more unified national approach to these patients is required.

We appreciate the paper by O'Dowd et al 1 as an interesting contribution to the literature concerning the primary care diagnosis of lung cancer. By concentrating on those patients dying soon after diagnosis, this paper is addressing the issue of access to care of patients with lung cancer who are already gravely ill. The disappointingly low chest X-ray (CXR) referral rates (we calculate obtained in only 40.2% and 50.4% of the patients attending with medium/high frequency and dying before and after 90 days, respectively) may represent irregular recording of CXR requests in The Health Improvement Network (THIN). Electronic research databases store their data in …

Lung cancer is a major global health burden with high incidence rates but poor long-term survival. Currently, the majority of cases are diagnosed at an advanced stage when surgical resection is not feasible. Screening for lung cancer has been a major focus of research for the last 40 years. Despite this, there is still a lack of evidence to promote its use outside clinical trials. More recently, interest has focused on promoting earlier recognition of symptomatic disease among both the general public and primary care physicians in order to encourage more timely investigation and referral to secondary care. The hope is that this approach may increase the proportion of disease identified in the early stages, allowing more surgical resections and improved five-year survival rates. This article provides an overview of the current evidence base in terms of early diagnosis of lung cancer and provides some examples of innovations to promote this.

Background\ud The ELCID Trial is a feasibility randomised controlled\ud trial examining the effect on lung cancer diagnosis of\ud giving an urgent chest x-ray to smokers, and recent exsmokers,\ud aged over 60 with new chest symptoms.\ud Aims\ud The qualitative component explores the feasibility of\ud individually randomising patients to an urgent CXR or\ud not and investigates any barriers to patient participation.\ud Methods\ud To date we have conducted semi-structured interviews\ud with six primary care staff (practice managers, research\ud nurses), ten patients randomised to ‘extra-NICE’ guidelines\ud for referral for urgent chest x-ray, and six patients\ud randomised to ‘usual care’ (NICE guidelines)). We hope\ud to also interview patients who decline randomisation.\ud Interviews were analysed using a Framework approach.\ud Results\ud Initial analysis indicated that practices have struggled to\ud recruit patients, partly due to the eligibility criteria that\ud requires ex-smokers to have stopped smoking within the\ud last five years. Practices with a research nurse have\ud recruited the most patients. Patients indicated that they\ud are happy to take part in the trial and their anxiety\ud levels were not raised. Most patients hoped to be\ud randomised to urgent chest x-ray, although those who\ud were not did not go back to their GP to request one.\ud Conclusions\ud Eligibility criteria needed revision to include ex-smokers\ud of any duration. These preliminary findings suggest that\ud the trial appears to be feasible and patients are happy to\ud accept randomisation. The findings will inform the\ud design of the main trial in the future.