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Abstract Background The feasibility of randomized trials often depends on successful patient recruitment. Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most. Also, most surveys have focused on the patients' perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention. Therefore, our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment. Methods We identified any potential recruitment barriers from the literature and from our own experience with a multi-center trial of respiratory rehabilitation in patients with chronic obstructive pulmonary disease. We developed and pilot-tested a self-administered questionnaire where recruiting physicians were asked to express their agreement with statements about recruitment barriers on a Likert-type scale from 1 (full agreement with statement = very substantial recruitment barrier) to 7 (no agreement with statement = no recruitment barrier). Results 38 of 55 recruiting physicians returned questionnaires (69% response rate), of which 35 could be analyzed (64% useable response rate). Recruiting physicians reported that "time constraints" (median agreement of 3, interquartile range 2–5) had the most negative impact on recruitment followed by "difficulties including identified eligible patients" (median agreement of 5, IQR 3–6). Other barriers such as "trial design barriers", "lack of access to treatment", "individual barriers of recruiting physicians" or "insufficient training of recruiting physicians" were perceived to have little or no impact on patient recruitment. Conclusion Physicians perceived time constraints as the most relevant recruitment barrier in a randomized trial. To overcome recruitment barriers interventions, that are affordable for both industry- and investigator-driven trials, need to be developed and tested in randomized trials. Trial registration ISRCTN84612310

Abstract Background Interpretation of the Hospital Anxiety and Depression Scale (HADS), commonly used to assess anxiety and depression in COPD patients, is unclear. Since its minimal important difference has never been established, our aim was to determine it using several approaches. Methods 88 COPD patients with FEV1 ≤ 50% predicted completed the HADS and other patient-important outcome measures before and after an inpatient respiratory rehabilitation. For the anchor-based approach we determined the correlation between the HADS and the anchors that have an established minimal important difference (Chronic Respiratory Questionnaire [CRQ] and Feeling Thermometer). If correlations were ≥ 0.5 we performed linear regression analyses to predict the minimal important difference from the anchors. As distribution-based approach we used the Effect Size approach. Results Based on CRQ emotional function and mastery domain as well as on total scores, the minimal important difference was 1.41 (95% CI 1.18–1.63) and 1.57 (1.37–1.76) for the HADS anxiety score and 1.68 (1.48–1.87) and 1.60 (1.38–1.82) for the HADS total score. Correlations of the HADS depression score and CRQ domain and Feeling Thermometer scores were < 0.5. Based on the Effect Size approach the MID of the HADS anxiety and depression score was 1.32 and 1.40, respectively. Conclusion The minimal important difference of the HADS is around 1.5 in COPD patients corresponding to a change from baseline of around 20%. It can be used for the planning and interpretation of trials.

Abstract Background The aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women. Methods In a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults) current smokers in 1991 (18 – 60 yrs) were reassessed in 2002 (n = 1792). Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years. Results In both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV1 was -10.4 mL(95%CI -15.3, -5.5) per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1) in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05) but this was not seen in men (-14.3 vs -8.8 mL p = 0.49). Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV1 was three fold higher in participants with FEV1/FVC Conclusion There are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.

Abstract Background There is a controversy about the additional benefit of various supplemental interventions used in clinical practice to further enhance the effectiveness of respiratory rehabilitation in patients with Chronic obstructive pulmonary disease (COPD). The aim of this research was to assess randomised controlled trials (RCTs) testing the additional benefit of supplemental interventions during respiratory rehabilitation in COPD patients. Methods Systematic review with literature searches in six electronic databases, extensive hand-searching and contacting of authors. Two reviewers selected independently eligible RCTs, rated the methodological quality and extracted the data, which were analyzed considering the minimal important difference of patient-important outcomes where possible. Findings We identified 20 RCTs whereof 18 provided sufficient data for analysis. The methodological quality was low and sample sizes were too small for most trials to produce meaningful results (median total sample size = 28). Data from five trials showed that supplemental oxygen during exercise did not have clinically meaningful effects on health-related quality of life while improvements of exercise capacity may be even larger for patients exercising on room air. RCTs of adding assisted ventilation, nutritional supplements or a number of anabolically acting drugs do not provide sufficient evidence for or against the use any of these supplemental interventions. Interpretation There is insufficient evidence for most supplemental interventions during respiratory rehabilitation to estimate their additional value, partly due to methodological shortcomings of included RCTs. Current data do not suggest benefit from supplemental oxygen during exercise, although the methodological quality of included trials limits conclusions. To appropriately assess any of the various supplemental interventions used in clinical practice, pragmatic trials on respiratory rehabilitation of COPD patients need to consider methodological aspects as well as appropriate sample sizes.

Abstract Background Physical exercise has become a cornerstone of management of chronic obstructive pulmonary disease (COPD) because it leads to clinically relevant improvements of exercise capacity and health-related quality of life (HRQL). Despite the scarcity of randomised trials directly comparing exercise protocols, current guidelines recommend high intensity continuous exercise for lower extremities as the probably most effective exercise modality. However, for patients admitted to inpatient respiratory rehabilitation programmes, it is often difficult to initiate such an exercise programme because they are severely limited by dyspnoea and leg fatigue and therefore unable to perform continuous exercise at higher intensities and for periods longer than 30 minutes. Interval exercise may be an attractive alternative for these COPD patients because it allows high intensity exercise with recovery periods. The aim of this study is to assess if interval exercise compared to high intensity continuous exercise is not of inferior effectiveness in terms of HRQL and exercise capacity improvements but associated with better exercise tolerance in patients with moderate to severe COPD at the beginning of a respiratory rehabilitation. Methods/Design We will assign patients with moderately severe to severe COPD to either continuous exercise or interval exercise using a stratified randomisation. Patients will follow 12–15 exercise sessions during a comprehensive inpatient respiratory rehabilitation. Primary end point for effectiveness is HRQL as measured by the Chronic Respiratory Questionnaire (CRQ) two weeks after the end of rehabilitation and secondary endpoints include additional clinical outcomes such as functional exercise capacity, other HRQL measures, patients' experience of physical exercise as well as physiological measures of the effects of physical exercise such as cardiopulmonary exercise testing. Including expected drop-outs, we will need 52 patients per group to show differences corresponding to the minimal clinically important difference of the CRQ. Outcome assessors and investigators involved in data analysis will be blinded to group assignment until analyses have been carried out. Discussion Clinicians and the scientific community need evidence on the benefits and tolerance of exercise protocols available in clinical practice. The proposed trial will provide important and needed data on interval and continuous exercise for decision making in clinical practice.

Abstract Background Assessment of health-related quality of life (HRQL) is important in patients with chronic obstructive pulmonary disease (COPD). Despite the high prevalence of COPD in Germany, Switzerland and Austria there is no validated disease-specific instrument available. The objective of this study was to translate the Chronic Respiratory Questionnaire (CRQ), one of the most widely used respiratory HRQL questionnaires, into German, develop an interviewer- and self-administered version including both standardised and individualised dyspnoea questions, and validate these versions in two randomised studies. Methods We recruited three groups of patients with COPD in Switzerland, Germany and Austria. The 44 patients of the first group completed the CRQ during pilot testing to adapt the CRQ to German-speaking patients. We then recruited 80 patients participating in pulmonary rehabilitation programs to assess internal consistency reliability and cross-sectional validity of the CRQ. The third group consisted of 38 patients with stable COPD without an intervention to assess test-retest reliability. To compare the interviewer- and self-administered versions, we randomised patients in groups 2 and 3 to the interviewer- or self-administered CRQ. Patients completed both the standardised and individualised dyspnoea questions. Results For both administration formats and all domains, we found good internal consistency reliability (Crohnbach's alpha between 0.73 and 0.89). Cross-sectional validity tended to be better for the standardised compared to the individualised dyspnoea questions and cross-sectional validity was slightly better for the self-administered format. Test-retest reliability was good for both the interviewer-administered CRQ (intraclass correlation coefficients for different domains between 0.81 and 0.95) and the self-administered format (intraclass correlation coefficients between 0.78 and 0.86). Lower within-person variability was responsible for the higher test-retest reliability of the interviewer-administered format while between person variability was similar for both formats. Conclusions Investigators in German-speaking countries can choose between valid and reliable self-and interviewer-administered CRQ formats.

Cathode formulation, which describes the amount of cathode active material (CAM), conductive additives (CAs), and binder within a cathode compound, is decisive for the performance metrics of lithium-ion battery (LIB) cells. The direct measurement of electronic resistance can be an enabler for more time- and cost-efficient cathode formulation improvements. Within this work, we correlate the electronic resistance with the electrochemical performance of cathodes. Two different high Nickel NCM cathode materials and numerous CAs are used to validate the findings. A detailed look into the resistance reduction potential of carbon black (CB) and single-walled carbon nanotubes (SWCNT) and their mixtures is made. Finally, an impact estimation of cathode formulation changes on LIB key performance factors, such as energy density and cost, is shown. [ABSTRACT FROM AUTHOR]

Thanks to their formidable electron transport properties, III–V compound semiconductors have established themselves as a possible alternative to strained-Si as future n-type logic switches. To predict the performance of such transistors, device simulators that can capture the peculiarities of the III–V band structure at low computational cost are required. In particular, their strong band non-parabolicity (NP) calls for advanced models going beyond the standard effective mass approximation (EMA). Previous studies have suggested ways to include NP effects into quantum transport calculations in the ballistic limit. Here, such a model is extended to account for electron–phonon interactions. It combines the non-equilibrium Green's function formalism and the EMA with NP corrections. The proposed method is validated through simulations of InGaAs nanowire field-effect transistors. The results are compared to full-band tight-binding calculations and to the solution of the subband Boltzmann transport equation, showing excellent agreement. [ABSTRACT FROM AUTHOR]

Little evidence on the validity of simple and widely applicable tools to predict mortality in patients with chronic obstructive pulmonary disease (COPD) exists. To conduct a large international study to validate the ADO index that uses age, dyspnoea and FEV(1) to predict 3-year mortality and to update it in order to make prediction of mortality in COPD patients as generalisable as possible. Individual subject data analysis of 10 European and American cohorts (n=13 914). Population-based, primary, secondary and tertiary care. COPD GOLD stages I-IV. We validated the original ADO index. We then obtained an updated ADO index in half of our cohorts to improve its predictive accuracy, which in turn was validated comprehensively in the remaining cohorts using discrimination, calibration and decision curve analysis and a number of sensitivity analyses. 1350 (9.7%) of all subjects with COPD (60% male, mean age 61 years, mean FEV(1) 66% predicted) had died at 3 years. The original ADO index showed high discrimination but poor calibration (p

Startups are a key force driving economic development, and the success of these high-risk ventures can bring huge profits to venture capital firms. The ability to predict the success of startups is a major advantage for investors to outperform their competitors. In this study, we explore the potential of using publicly available LinkedIn profiles as an alternative and complementary data source to Crunchbase for predicting startup success. We provide a comprehensive review of the existing literature on the factors that influence startup success to create a large set of features for predictive modeling. We train two models for predicting startup success employing light gradient boosting that use LinkedIn data as a standalone and as a complementary data source, and compare them to baseline models based on Crunchbase data. We show that using LinkedIn as a complementary data source yields the best result with a mean area under the curve (AUC) value of 84%. We also provide a thorough analysis of what types of information contribute most to modeling startup success using the Shapley value method. Our models and analysis can be used to develop a decision support system to facilitate startup screening and the due diligence process for venture capital firms. [ABSTRACT FROM AUTHOR]