Background Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non–small-cell lung cancer (NSCLC). We ...hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy. Methods Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. Responding patients were subsequently randomly assigned to surgical resection or radiotherapy. Survival curves were estimated using Kaplan–Meier analyses from time of randomization. Results Induction chemotherapy resulted in a response rate of 61% (95% confidence interval CI = 57% to 65%) among the 579 eligible patients. A total of 167 patients were allocated to resection and 165 to radiotherapy. Of the 154 (92%) patients who underwent surgery, 14% had an exploratory thoracotomy, 50% a radical resection, 42% a pathologic downstaging, and 5% a pathologic complete response; 4% died after surgery. Postoperative radiotherapy was administered to 62 (40%) of patients in the surgery arm. Among the 154 (93%) irradiated patients, overall compliance to the radiotherapy prescription was 55%, and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7%; one patient died of radiation pneumonitis. Median and 5-year overall survival for patients randomly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (hazard ratio = 1.06, 95% CI = 0.84 to 1.35). Rates of progression-free survival were also similar in both groups. Conclusion In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy, surgical resection did not improve overall or progression-free survival compared with radiotherapy. In view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these patients.
Cardiac tissue engineering is a promising approach to treat cardiovascular diseases, which are a major socio-economic burden worldwide. An optimal material for cardiac tissue engineering, allowing ...cardiomyocyte attachment and exhibiting proper immunocompatibility, biocompatibility and mechanical characteristics, has not yet emerged. An additional challenge is to develop a fabrication method that enables the generation of proper hierarchical structures and constructs with a high density of cardiomyocytes for optimal contractility. Thus, there is a focus on identifying suitable materials for cardiac tissue engineering. Here, we investigated the interaction of neonatal rat heart cells with engineered spider silk protein (eADF4(C16)) tagged with the tripeptide arginyl-glycyl-aspartic acid cell adhesion motif RGD, which can be used as coating, but can also be 3D printed. Cardiomyocytes, fibroblasts, and endothelial cells attached well to eADF4(C16)-RGD coatings, which did not induce hypertrophy in cardiomyocytes, but allowed response to hypertrophic as well as proliferative stimuli. Furthermore, Kymograph and MUSCLEMOTION analyses showed proper cardiomyocyte beating characteristics on spider silk coatings, and cardiomyocytes formed compact cell aggregates, exhibiting markedly higher speed of contraction than cardiomyocyte mono-layers on fibronectin. The results suggest that eADF4(C16)-RGD is a promising material for cardiac tissue engineering.
Workplace-Based Assessment (WBA) plays a pivotal role in present-day competency-based medical curricula. Validity in WBA mainly depends on how stakeholders (e.g. clinical supervisors and learners) ...use the assessments—rather than on the intrinsic qualities of instruments and methods. Current research on assessment in clinical contexts seems to imply that variable behaviours during performance assessment of both assessors and learners may well reflect their respective beliefs and perspectives towards WBA. We therefore performed a Q methodological study to explore perspectives underlying stakeholders’ behaviours in WBA in a postgraduate medical training program. Five different perspectives on performance assessment were extracted: Agency, Mutuality, Objectivity, Adaptivity and Accountability. These perspectives reflect both differences and similarities in stakeholder perceptions and preferences regarding the utility of WBA. In comparing and contrasting the various perspectives, we identified two key areas of disagreement, specifically ‘the locus of regulation of learning’ (i.e., self-regulated versus externally regulated learning) and ‘the extent to which assessment should be standardised’ (i.e., tailored versus standardised assessment). Differing perspectives may variously affect stakeholders’ acceptance, use—and, consequently, the effectiveness—of assessment programmes. Continuous interaction between all stakeholders is essential to monitor, adapt and improve assessment practices and to stimulate the development of a shared mental model. Better understanding of underlying stakeholder perspectives could be an important step in bridging the gap between psychometric and socio-constructivist approaches in WBA.
In medical residency, performance observations are considered an important strategy to monitor competence development, provide feedback and warrant patient safety. The aim of this study was to gain ...insight into whether and how supervisor-resident dyads build a working repertoire regarding the use of observations, and how they discuss and align goals and approaches to observation in particular.
We used a qualitative, social constructivist approach to explore if and how supervisory dyads work towards alignment of goals and preferred approaches to performance observations. We conducted semi-structured interviews with supervisor-resident dyads, performing a template analysis of the data thus obtained.
The supervisory dyads did not frequently communicate about the use of observations, except at the start of training and unless they were triggered by internal or external factors. Their working repertoire regarding the use of observations seemed to be primarily driven by patient safety goals and institutional assessment requirements rather than by providing developmental feedback. Although intended as formative, the institutional test was perceived as summative by supervisors and residents, and led to teaching to the test rather than educating for purposes of competence development.
To unlock the full educational potential of performance observations, and to foster the development of an educational alliance, it is essential that supervisory dyads and the training institute communicate clearly about these observations and the role of assessment practices of- and for learning, in order to align their goals and respective approaches.
We report the discovery of nine previously unknown gamma-ray pulsars in a blind search of data from the Fermi Large Area Telescope (LAT). The pulsars were found with a novel hierarchical search ...method originally developed for detecting continuous gravitational waves from rapidly rotating neutron stars. Designed to find isolated pulsars spinning at up to kHz frequencies, the new method is computationally efficient and incorporates several advances, including a metric-based gridding of the search parameter space (frequency, frequency derivative, and sky location) and the use of photon probability weights. The nine pulsars have spin frequencies between 3 and 12 Hz, and characteristic ages ranging from 17 kyr to 3 Myr. Two of them, PSRs J1803-2149 and J2111+ 4606, are young and energetic Galactic-plane pulsars (spin-down power above 6 x 10 super(35) erg s super(-1) and ages below 100 kyr). The seven remaining pulsars, PSRs J0106+4855, J0622+3749, J1620-4927, J1746-3239, J2028+3332, J2030+4415, and J2139+4716, are older and less energetic; two of them are located at higher Galactic latitudes (b > 10degrees). PSR J0106+4855 has the largest characteristic age (3 Myr) and the smallest surface magnetic field (2 x 10 super(11) G) of all LAT blind-search pulsars. PSR J2139+4716 has the lowest spin-down power (3 x 10 super(33) erg s super(-1)) among all non-recycled gamma-ray pulsars ever found. Despite extensive multi-frequency observations, only PSR JO 106+4855 has detectable pulsations in the radio band. The other eight pulsars belong to the increasing population of radio-quiet gamma-ray pulsars.
Direct observation of clinical task performance plays a pivotal role in competency-based medical education. Although formal guidelines require supervisors to engage in direct observations, research ...demonstrates that trainees are infrequently observed. Supervisors may not only experience practical and socio-cultural barriers to direct observations in healthcare settings, they may also question usefulness or have low perceived self-efficacy in performing direct observations. A better understanding of how these multiple factors interact to influence supervisors' intention to perform direct observations may help us to more effectively implement the aforementioned guidelines and increase the frequency of direct observations.
We conducted an exploratory quantitative study, using the Theory of Planned Behaviour (TPB) as our theoretical framework. In applying the TPB, we transfer a psychological theory to medical education to get insight in the influence of cognitive and emotional processes on intentions to use direct observations in workplace based learning and assessment. We developed an instrument to investigate supervisors intention to perform direct observations. The relationships between the TPB measures of our questionnaire were explored by computing bivariate correlations using Pearson's R tests. Hierarchical regression analysis was performed in order to assess the impact of the respective TPB measures as predictors on the intention to perform direct observations.
In our study 82 GP supervisors completed our TPB questionnaire. We found that supervisors had a positive attitude towards direct observations. Our TPB model explained 45% of the variance in supervisors' intentions to perform them. Normative beliefs and past behaviour were significant determinants of this intention.
Our study suggests that supervisors use their past experiences to form intentions to perform direct observations in a careful, thoughtful manner and, in doing so, also take the preferences of the learner and other stakeholders potentially engaged in direct observations into consideration. These findings have potential implications for research into work-based assessments and the development of training interventions to foster a shared mental model on the use of direct observations.
Prophylactic cranial irradiation (PCI) in patients with extensive-disease small-cell lung cancer (ED-SCLC) leads to significantly fewer symptomatic brain metastases and improved survival. Detailed ...effects of PCI on health-related quality of life (HRQOL) are reported here.
Patients (age, 18 to 75 years; WHO < or = 2) with ED-SCLC, and any response to chemotherapy, were randomly assigned to either observation or PCI. Health-related quality of life (HRQOL) and patient-reported symptoms were secondary end points. The European Organisation for the Research and Treatment of Cancer core HRQOL tool (Quality of Life Questionnaire C30) and brain module (Quality of Life Questionnaire Brain Cancer Module) were used to collect self-reported patient data. Six HRQOL scales were selected as primary HRQOL end points: global health status; hair loss; fatigue; and role, cognitive and emotional functioning. Assessments were performed at random assignment, 6 weeks, 3 months, and then 3-monthly up to 1 year and 6-monthly thereafter.
Compliance with the HRQOL assessment was 93.7% at baseline and dropped to 60% at 6 weeks. Short-term results up to 3 months showed that there was a negative impact of PCI on selected HRQOL scales. The largest mean difference between the two arms was observed for fatigue and hair loss. The impact of PCI on global health status as well as on functioning scores was more limited. For global health status, the observed mean difference was eight points on a scale 0 to 100 at 6 weeks (P = .018) and 3 months (P = .055).
PCI should be offered to all responding ED SCLC patients. Patients should be informed of the potential adverse effects from PCI. Clinicians should be alert to these; monitor their patients; and offer appropriate support, clinical, and psychosocial care.
It is challenging to change physicians' antimicrobial prescribing behaviour. Although antimicrobial prescribing is determined by contextual (e.g. a lack of guidelines), cultural (e.g. peer practice) ...and behavioural (e.g. perceived decision making autonomy) factors, most antimicrobial stewardship programmes fail to consider these factors in their approach. This may lead to suboptimal intervention effectiveness. We present a new approach in antimicrobial stewardship programme development that addresses relevant determinants of antimicrobial prescribing: participatory action research (PAR). PAR is a collaborative process that aims to bring about change in social situations by producing practical knowledge that is useful in local practice. It requires substantial involvement of relevant stakeholders to address determinants of the studied behaviour and to facilitate empowerment. PAR is well suited for complex problems in multidisciplinary settings as it adapts to local needs, delivering a tailored approach to improving local practice. We describe how PAR can be applied to antimicrobial stewardship, and describe the PAR design of two ongoing multicentre antimicrobial stewardship projects, in the acute care setting and the long-term care setting, respectively.
We reviewed the literature on instruments for work-based assessment in single clinical encounters, such as the mini-clinical evaluation exercise (mini-CEX), and examined differences between these ...instruments in characteristics and feasibility, reliability, validity and educational effect. A PubMed search of the literature published before 8 January 2009 yielded 39 articles dealing with 18 different assessment instruments. One researcher extracted data on the characteristics of the instruments and two researchers extracted data on feasibility, reliability, validity and educational effect. Instruments are predominantly formative. Feasibility is generally deemed good and assessor training occurs sparsely but is considered crucial for successful implementation. Acceptable reliability can be achieved with 10 encounters. The validity of many instruments is not investigated, but the validity of the mini-CEX and the ‘clinical evaluation exercise’ is supported by strong and significant correlations with other valid assessment instruments. The evidence from the few studies on educational effects is not very convincing. The reports on clinical assessment instruments for single work-based encounters are generally positive, but supporting evidence is sparse. Feasibility of instruments seems to be good and reliability requires a minimum of 10 encounters, but no clear conclusions emerge on other aspects. Studies on assessor and learner training and studies examining effects beyond ‘happiness data’ are badly needed.
Free tropospheric aerosol was sampled at the Pico Mountain Observatory located at 2225 m above mean sea level on Pico Island of the Azores archipelago in the North Atlantic. The observatory is ...located ~ 3900 km east and downwind of North America, which enables studies of free tropospheric air transported over long distances. Aerosol samples collected on filters from June to October 2012 were analyzed to characterize organic carbon, elemental carbon, and inorganic ions. The average ambient concentration of aerosol was 0.9 plus or minus 0.7 mu g m-3. On average, organic aerosol components represent the largest mass fraction of the total measured aerosol (60 plus or minus 51%), followed by sulfate (23 plus or minus 28%), nitrate (13 plus or minus 10%), chloride (2 plus or minus 3%), and elemental carbon (2 plus or minus 2%). Water-soluble organic matter (WSOM) extracted from two aerosol samples (9/24 and 9/25) collected consecutively during a pollution event were analyzed using ultrahigh-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Approximately 4000 molecular formulas were assigned to each of the mass spectra in the range of m/z 100-1000. The majority of the assigned molecular formulas had unsaturated structures with CHO and CHNO elemental compositions. FLEXPART retroplume analyses showed the sampled air masses were very aged (average plume age > 12 days). These aged aerosol WSOM compounds had an average O/C ratio of ~ 0.45, which is relatively low compared to O/C ratios of other aged aerosol. The increase in aerosol loading during the measurement period of 9/24 was linked to biomass burning emissions from North America by FLEXPART retroplume analysis and Moderate Resolution Imaging Spectroradiometer (MODIS) fire counts. This was confirmed with biomass burning markers detected in the WSOM and with the morphology and mixing state of particles as determined by scanning electron microscopy. The presence of markers characteristic of aqueous-phase reactions of phenolic species suggests that the aerosol collected at the Pico Mountain Observatory had undergone cloud processing before reaching the site. Finally, the air masses of 9/25 were more aged and influenced by marine emissions, as indicated by the presence of organosulfates and other species characteristic of marine aerosol. The change in the air masses for the two samples was corroborated by the changes in ethane, propane, and ozone, morphology of particles, as well as by the FLEXPART retroplume simulations. This paper presents the first detailed molecular characterization of free tropospheric aged aerosol intercepted at a lower free troposphere remote location and provides evidence of low oxygenation after long-range transport. We hypothesize this is a result of the selective removal of highly aged and polar species during long-range transport, because the aerosol underwent a combination of atmospheric processes during transport facilitating aqueous-phase removal (e.g., clouds processing) and fragmentation (e.g., photolysis) of components.
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