Background

Changes in host tumor genome DNA methylation patterns are among the molecular alterations associated with HPV-related carcinogenesis. However, there is little known about the epigenetic changes associated specifically with the development of anal squamous cell cancer (SCC). We sought to characterize broad methylation profiles across the spectrum of anal squamous neoplasia.

Methodology/Principal Findings

Twenty-nine formalin-fixed paraffin embedded samples from 24 patients were evaluated and included adjacent histologically normal anal mucosa (NM; n = 3), SCC-in situ (SCC-IS; n = 11) and invasive SCC (n = 15). Thirteen women and 11 men with a median age of 44 years (range 26–81) were included in the study. Using the SFP10 LiPA HPV-typing system, HPV was detected in at least one tissue from all patients with 93% (27/29) being positive for high-risk HPV types and 14 (93%) of 15 invasive SCC tissues testing positive for HPV 16. Bisulfite-modified DNA was interrogated for methylation at 1,505 CpG loci representing 807 genes using the Illumina GoldenGate Methylation Array. When comparing the progression from normal anal mucosa and SCC-IS to invasive SCC, 22 CpG loci representing 20 genes demonstrated significant differential methylation (p<0.01). The majority of differentially methylated gene targets occurred at or close to specific chromosomal locations such as previously described HPV methylation “hotspots” and viral integration sites.

Conclusions

We have identified a panel of differentially methlylated CpG loci across the spectrum of HPV-associated squamous neoplasia of the anus. To our knowledge, this is the first reported application of large-scale high throughput methylation analysis for the study of anal neoplasia. Our findings support further investigations into the role of host-genome methylation in HPV-associated anal carcinogenesis with implications towards enhanced diagnosis and screening strategies.

We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20+ B cell follicles with prominent areas of CD3+ T cells (both CD4+ and CD8+ subsets). CD86+, but not FoxP3+, cells were present within these unique structures as well. The direct correlation between the 12-chemokine GES score and the presence of unique, lymph nodal structures was also associated with better overall survival of the subset of melanoma patients. The use of this novel 12-chemokine GES may reveal basic information on in situ mechanisms of the anti-tumor immune response, potentially leading to improvements in the identification and selection of melanoma patients most suitable for immunotherapy.

Objective

To examine possible social variations in lung cancer survival and assess if any such gradients can be attributed to social differences in comorbidity, stage at diagnosis or treatment.

Design

Population-based cohort identified in the Thames Cancer Registry.

Setting

South East England.

Participants

15 582 lung cancer patients diagnosed between 2006 and 2008.

Main outcome measures

Stage at diagnosis, surgery, radiotherapy, chemotherapy and survival.

Results

The likelihood of being diagnosed as having early-stage disease did not vary by socioeconomic quintiles (p=0.58). In early-stage non-small-cell lung cancer, the likelihood of undergoing surgery was lowest in the most deprived group. There were no socioeconomic differences in the likelihood of receiving radiotherapy in stage III disease, while in advanced disease and in small-cell lung cancer, receipt of chemotherapy differed over socioeconomic quintiles (p<0.01). In early-stage disease and following adjustment for confounders, the HR between the most deprived and the most affluent group was 1.24 (95% CI 0.98 to 1.56). Corresponding estimates in stage III and advanced disease or small-cell lung cancer were 1.16 (95% CI 1.01 to 1.34) and 1.12 (95% CI 1.05 to 1.20), respectively. In early-stage disease, the crude HR between the most deprived and the most affluent group was approximately 1.4 and constant through follow-up, while in patients with advanced disease or small-cell lung cancer, no difference was detectable after 3 months.

Conclusion

We observed socioeconomic variations in management and survival in patients diagnosed as having lung cancer in South East England between 2006 and 2008, differences which could not fully be explained by social differences in stage at diagnosis, co-morbidity and treatment. The survival observed in the most affluent group should set the target for what is achievable for all lung cancer patients, managed in the same healthcare system.

Article summary

Article focus

Social differences in management and survival in lung cancer patients.

Particular focus on possible social variations in lung cancer survival and assess if any such gradients can be attributed to social differences in co-morbidity, stage at diagnosis or treatment.

Key messages

There were no detectable socioeconomic differences in stage at diagnosis among lung cancer patients in South East England between 2006 and 2008.

Socioeconomic differences in lung cancer management and survival existed. The observed inequalities in survival could not fully be explained by social differences in stage at diagnosis, co-morbidity and treatment factors.

In early-stage disease, social gradients in survival existed throughout follow-up, whereas in advanced disease, variations in survival were confined to the period immediately after diagnosis.

Strengths and limitations of this study

Strengths included the population-based cohort design. The material at hand allowed analyses that accounted for co-morbidity, stage at diagnosis and treatment factors.

Limitations included the absence of data on performance status, forced expiratory volume, smoking history and lifestyle factors.

Background

Healthcare professionals have shown concern about performing mouth-to-mouth ventilation due to the risks to themselves with the procedure. However, little is known about healthcare professionals' fears and attitudes to start CPR and the impact of training.

Objective

To examine whether there were any changes in the attitudes among healthcare professionals to performing CPR from before to after training.

Methods

Healthcare professionals from two Swedish hospitals were asked to answer a questionnaire before and after training. The questions were relating to physical and mental discomfort and attitudes to CPR. Statistical analysis used was generalized McNemar's test.

Results

Overall, there was significant improvement in 10 of 11 items, reflecting various aspects of attitudes to CPR.

All groups of health care professionals (physicians, nurses, assistant nurses, and "others" = physiotherapists, occupational therapists, social welfare officers, psychologists, biomedical analysts) felt more secure in CPR knowledge after education. In other aspects, such as anxiety prior to a possible cardiac arrest, only nurses and assistant nurses improved.

The concern about being infected, when performing mouth to mouth ventilation, was reduced with the most marked reduction in physicians (75%; P < 0.001).

Conclusion

In this hospital-based setting, we found a positive outcome of education and training in CPR concerning healthcare professionals' attitudes to perform CPR. They felt more secure in their knowledge of cardiopulmonary resuscitation. In some aspects of attitudes to resuscitation nurses and assistant nurses appeared to be the groups that were most markedly influenced. The concern of being infected by a disease was low.

Background

D-CPR (Defibrillator Cardiopulmonary Resuscitation) is a technique for optimal basic life support during cardiopulmonary resuscitation (CPR). Guidelines recommend that healthcare professionals can perform CPR with competence. How CPR training and provision is organized varies between hospitals, and it is our impression that in Sweden this has generally improved during the last 15-20 years. However, some hospitals still do not have any AED (Automated External Defibrillators). The aim was to investigate potential differences in practical skills between different healthcare professions before and after training in D-CPR.

Methods

Seventy-four healthcare professionals were video recorded and evaluated for adherence to a modified Cardiff Score. A Laerdal Resusci Anne manikin in connection to PC Skill reporting System was used to evaluate CPR quality. A simulated CPR situation was accomplished during a 5-10 min scenario of ventricular fibrillation. Paired and unpaired statistical methods were used to examine differences within and between occupations with respect to the intervention.

Results

There were no differences in skills among the different healthcare professions, except for compressions per minute. In total, the number of compression per minute and depth improved for all groups (P < 0.001). In total, 41% of the participants used AED before and 96% of the participants used AED after the intervention (P < 0.001). Before intervention, it took a median time of 120 seconds until the AED was used; after the intervention, it took 82 seconds.

Conclusion

Nearly all healthcare professionals learned to use the AED. There were no differences in CPR skill performances among the different healthcare professionals.

Background

All eukaryotic organisms need to distinguish each of their chromosomes. A few protein complexes have been described that recognise entire, specific chromosomes, for instance dosage compensation complexes and the recently discovered autosome-specific Painting of Fourth (POF) protein in Drosophila. However, no sequences have been found that are chromosome-specific and distributed over the entire length of the respective chromosome. Here, we present a new, unbiased, exhaustive computational method that was used to probe three Drosophila genomes for chromosome-specific sequences.

Results

By combining genome annotations and cytological data with multivariate statistics related to three Drosophila genomes we found sequence signatures that distinguish Muller's F-elements (chromosome 4 in D. melanogaster) from all other chromosomes in Drosophila that are not attributable to differences in nucleotide composition, simple sequence repeats or repeated elements. Based on these signatures we identified complex motifs that are strongly overrepresented in the F-elements and found indications that the D. melanogaster motif may be involved in POF-binding to the F-element. In addition, the X-chromosomes of D. melanogaster and D. yakuba can be distinguished from the other chromosomes, albeit to a lesser extent. Surprisingly, the conservation of the F-element sequence signatures extends not only between species separated by approximately 55 Myr, but also linearly along the sequenced part of the F-elements.

Conclusion

Our results suggest that chromosome-distinguishing features are not exclusive to the sex chromosomes, but are also present on at least one autosome (the F-element) in Drosophila.