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1.  Biopsy testing in an inoperable, non-small cell lung cancer population—a retrospective, real-life study in Sweden 
Journal of Thoracic Disease  2015;7(12):2226-2233.
Correct diagnosis and staging are required for optimal treatment choice in lung cancer patients. This retrospective, patient medical records study investigated the clinical practice of lung cancer biopsy procedures and testing in Sweden.
Consecutive patients with a recorded inoperable, malignant tumour of bronchus and lung were retrospectively identified at geographically widespread pulmonology clinics (NCT01139619). Data, including diagnostic sampling methodology [bronchoscopy, biopsy by pulmonologist and computed tomography (CT)-guided biopsy], were collected for patients diagnosed between 1 June 2009–31 May 2010, and analysed using descriptive statistics. A study-predefined algorithm, including six criteria on tumour localization and size, forced expiratory volume in one second (FEV1), blood saturation and risk of bleeding theoretically categorizing patient suitability for CT-guided biopsy, was used.
In total, 132 patients (mean age 68 years, 48% women, 61% adenocarcinoma, 86% current/ former smokers, 96% performance status ≤2, mean FEV1 volume ≥2 L) were included. The majority were examined by >1 diagnostic procedure (29% by CT-guided biopsy). Median overall time from first hospital contact to established diagnosis was 12.0 days (10.0 and 28.0 days for bronchoscopy and CT-guided biopsy, respectively). No major differences in lung function, age, performance status or predefined algorithm criteria were noted for patients examined by CT-guided biopsy versus bronchoscopy or biopsy. Complications were reported for 11 patients, including pneumothorax in six patients. Histopathology was used most frequently to diagnose and subtype (70%), although 66% of patients examined solely by bronchoscopy were diagnosed by cytology. For 26.5% of patients, epidermal growth factor receptor (EGFR) mutation testing was recorded.
No limitations regarding patient suitability or methodological complications were noted in this real-life, observational study. The CT-guided biopsy is a relatively safe and well-established method, and may need to be utilized further to fulfil current and future demands for faster diagnosis and high quality tissue as new tumour markers and targeted therapies become available.
PMCID: PMC4703673  PMID: 26793344
Non-small cell lung cancer (NSCLC); biopsy; medical records; pathology; epidermal growth factor receptor (EGFR)
3.  Multiple π-bands and Bernal stacking of multilayer graphene on C-face SiC, revealed by nano-Angle Resolved Photoemission 
Scientific Reports  2014;4:4157.
Only a single linearly dispersing π-band cone, characteristic of monolayer graphene, has so far been observed in Angle Resolved Photoemission (ARPES) experiments on multilayer graphene grown on C-face SiC. A rotational disorder that effectively decouples adjacent layers has been suggested to explain this. However, the coexistence of μm-sized grains of single and multilayer graphene with different azimuthal orientations and no rotational disorder within the grains was recently revealed for C-face graphene, but conventional ARPES still resolved only a single π-band. Here we report detailed nano-ARPES band mappings of individual graphene grains that unambiguously show that multilayer C-face graphene exhibits multiple π-bands. The band dispersions obtained close to the moreover clearly indicate, when compared to theoretical band dispersion calculated in the framework of the density functional method, Bernal (AB) stacking within the grains. Thus, contrary to earlier claims, our findings imply a similar interaction between graphene layers on C-face and Si-face SiC.
PMCID: PMC3932481  PMID: 24561727
4.  Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates 
Organic & biomolecular chemistry  2011;9(24):8356-8370.
Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying protein aggregation diseases. Here we report the chemical design of a library of anionic luminescent conjugated oligothiophenes (LCOs), which can be utilized as ligands for detection of protein aggregates. Certain molecular requirements were shown to be necessary for detecting: i) early non-thioflavinophilic protein assemblies of Aβ1-42 and insulin preceding the formation of amyloid fibrils and ii) for obtaining distinct spectral signatures of the two main pathological hallmarks observed in human Alzheimer’s diease brain tissue (Aβ plaques and neurofibrillary tangles). Our findings suggest that a superior anionic LCO based ligand should have a backbone consisting of five to seven thiophene units and carboxyl groups extending the conjugated thiophene backbone. Such LCOs will be highly useful for studying the underlying molecular events of protein aggregation diseases and could also be utilized for the development of novel diagnostic tools for these diseases.
PMCID: PMC3326384  PMID: 22051883
5.  Relation between smoking history and gene expression profiles in lung adenocarcinomas 
BMC Medical Genomics  2012;5:22.
Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers’ lung carcinomas remain to a large extent unclear.
Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets.
Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking.
Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history.
PMCID: PMC3447685  PMID: 22676229
Lung cancer; Smoking; Gene expression analysis; Adenocarcinoma; EGFR; Never-smokers; Immune response
6.  Panmixia in the European eel: a matter of time… 
The European eel (Anguilla anguilla L.) has been a prime example of the panmixia paradigm because of its extraordinary adaptation to the North Atlantic gyral system, semelparous spawning in the Sargasso Sea and long trans-oceanic migration. Recently, this view was challenged by the suggestion of a genetic structure characterized by an isolation-by-distance (IBD) pattern. This is only likely if spawning subpopulations are spatially and/or temporally separated, followed by non-random larval dispersal. A limitation of previous genetic work on eels is the lack of replication over time to test for temporal stability of genetic structure. Here, we hypothesize that temporal genetic variation plays a significant role in explaining the spatial structure reported earlier for this species. We tested this by increasing the texture of geographical sampling and by including temporal replicates. Overall genetic differentiation among samples was low, highly significant and comparable with earlier studies (FST=0.0014; p<0.01). On the other hand, and in sharp contrast with current understandings, hierarchical analyses revealed no significant inter-location genetic heterogeneity and hence no IBD. Instead, genetic variation among temporal samples within sites clearly exceeded the geographical component. Our results provide support for the panmixia hypothesis and emphasize the importance of temporal replication when assessing population structure of marine fish species.
PMCID: PMC1559815  PMID: 16024374
Anguilla anguilla; conservation; genetic structure; microsatellites; temporal variation
7.  Can pulsed ultrasound increase tissue damage during ischemia? A study of the effects of ultrasound on infarcted and non-infarcted myocardium in anesthetized pigs 
The same mechanisms by which ultrasound enhances thrombolysis are described in connection with non-beneficial effects of ultrasound. The present safety study was therefore designed to explore effects of beneficial ultrasound characteristics on the infarcted and non-infarcted myocardium.
In an open chest porcine model (n = 17), myocardial infarction was induced by ligating a coronary diagonal branch. Pulsed ultrasound of frequency 1 MHz and intensity 0.1 W/cm2 (ISATA) was applied during one hour to both infarcted and non-infarcted myocardial tissue. These ultrasound characteristics are similar to those used in studies of ultrasound enhanced thrombolysis. Using blinded assessment technique, myocardial damage was rated according to histopathological criteria.
Infarcted myocardium exhibited a significant increase in damage score compared to non-infarcted myocardium: 6.2 ± 2.0 vs. 4.3 ± 1.5 (mean ± standard deviation), (p = 0.004). In the infarcted myocardium, ultrasound exposure yielded a further significant increase of damage scores: 8.1 ± 1.7 vs. 6.2 ± 2.0 (p = 0.027).
Our results suggest an instantaneous additive effect on the ischemic damage in myocardial tissue when exposed to ultrasound of stated characteristics. The ultimate damage degree remains to be clarified.
PMCID: PMC1090565  PMID: 15831106

Results 1-7 (7)