Case series of trans-thoracic nodule aspirate performed by interventional pulmonologists

Percutaneous interventional tissue sampling of pulmonary masses and lymphadenopathy is a means for diagnosis of thoracic malignancy. The user base that can perform this skill with ultrasound guidance is expanding. A retrospective cohort of fine needle aspiration and percutaneous core biopsies was identified to evaluate their safety and efficacy. 47 distinct procedures were performed by a university medical center\u27s Interventional Pulmonary service between 2012 and 2018.39 consecutive procedures were diagnostically successful by percutaneous means, with 34 of the successful diagnoses based on fine needle aspiration alone. In our cohort by percutaneous biopsy the most common diagnosis was Non-Small Cell Lung Cancer with 28 samples, followed by Small Cell Lung Cancer with 7 samples as well as additional solitary diagnoses of suspected infection, Hepatocellular Cancer, Hodgkin Lymphoma and Malignant Melanoma. 4 procedures had complications, two of which resolved post procedure with observation and two pneumothoracies which resolved with chest tube placement and hospital observation. A wide variety of diagnoses were obtained with percutaneous biopsies with 83% of percutaneous biopsies performed by Interventional Pulmonologists achieving diagnostic success

The cultural role(s) of makerspaces

Makerspaces and maker programmes are evolving and expanding the roles they are undertaking. This is a work-in-progress summary as of September 2016. The segmentation proposed is an early stage exploration. This excerpt is taken from a presentation event examining the models and tools these spaces are using toward cultural end

Survival prediction in mesothelioma using a scalable lasso regression model: instructions for use and initial performance using clinical predictors

Introduction: Accurate prognostication is difficult in malignant pleural mesothelioma (MPM). We developed a set of robust computational models to quantify the prognostic value of routinely available clinical data, which form the basis of published MPM prognostic models. Methods: Data regarding 269 patients with MPM were allocated to balanced training (n=169) and validation sets (n=100). Prognostic signatures (minimal length best performing multivariate trained models) were generated by least absolute shrinkage and selection operator regression for overall survival (OS), OS <6 months and OS <12 months. OS prediction was quantified using Somers DXY statistic, which varies from 0 to 1, with increasing concordance between observed and predicted outcomes. 6-month survival and 12-month survival were described by area under the curve (AUC) scores. Results: Median OS was 270 (IQR 140–450) days. The primary OS model assigned high weights to four predictors: age, performance status, white cell count and serum albumin, and after cross-validation performed significantly better than would be expected by chance (mean DXY0.332 (±0.019)). However, validation set DXY was only 0.221 (0.0935–0.346), equating to a 22% improvement in survival prediction than would be expected by chance. The 6-month and 12-month OS signatures included the same four predictors, in addition to epithelioid histology plus platelets and epithelioid histology plus C-reactive protein (mean AUC 0.758 (±0.022) and 0.737 (±0.012), respectively). The <6-month OS model demonstrated 74% sensitivity and 68% specificity. The <12-month OS model demonstrated 63% sensitivity and 79% specificity. Model content and performance were generally comparable with previous studies. Conclusions: The prognostic value of the basic clinical information contained in these, and previously published models, is fundamentally of limited value in accurately predicting MPM prognosis. The methods described are suitable for expansion using emerging predictors, including tumour genomics and volumetric staging

Patterns of intron sequence evolution in Drosophila are dependent upon length and GC content

BACKGROUND: Introns comprise a large fraction of eukaryotic genomes, yet little is known about their functional significance. Regulatory elements have been mapped to some introns, though these are believed to account for only a small fraction of genome wide intronic DNA. No consistent patterns have emerged from studies that have investigated general levels of evolutionary constraint in introns. RESULTS: We examine the relationship between intron length and levels of evolutionary constraint by analyzing inter-specific divergence at 225 intron fragments in Drosophila melanogaster and Drosophila simulans, sampled from a broad distribution of intron lengths. We document a strongly negative correlation between intron length and divergence. Interestingly, we also find that divergence in introns is negatively correlated with GC content. This relationship does not account for the correlation between intron length and divergence, however, and may simply reflect local variation in mutational rates or biases. CONCLUSION: Short introns make up only a small fraction of total intronic DNA in the genome. Our finding that long introns evolve more slowly than average implies that, while the majority of introns in the Drosophila genome may experience little or no selective constraint, most intronic DNA in the genome is likely to be evolving under considerable constraint. Our results suggest that functional elements may be ubiquitous within longer introns and that these introns may have a more general role in regulating gene expression than previously appreciated. Our finding that GC content and divergence are negatively correlated in introns has important implications for the interpretation of the correlation between divergence and levels of codon bias observed in Drosophila

Reduced efficacy of selection in regions of the Drosophila genome that lack crossing over

BACKGROUND: The recombinational environment is predicted to influence patterns of protein sequence evolution through the effects of Hill-Robertson interference among linked sites subject to selection. In freely recombining regions of the genome, selection should more effectively incorporate new beneficial mutations, and eliminate deleterious ones, than in regions with low rates of genetic recombination. RESULTS: We examined the effects of recombinational environment on patterns of evolution using a genome-wide comparison of Drosophila melanogaster and D. yakuba. In regions of the genome with no crossing over, we find elevated divergence at nonsynonymous sites and in long introns, a virtual absence of codon usage bias, and an increase in gene length. However, we find little evidence for differences in patterns of evolution between regions with high, intermediate, and low crossover frequencies. In addition, genes on the fourth chromosome exhibit more extreme deviations from regions with crossing over than do other, no crossover genes outside the fourth chromosome. CONCLUSION: All of the patterns observed are consistent with a severe reduction in the efficacy of selection in the absence of crossing over, resulting in the accumulation of deleterious mutations in these regions. Our results also suggest that even a very low frequency of crossing over may be enough to maintain the efficacy of selection

Association of polymorphisms in genes of factors involved in regulation of splicing of cystic fibrosis transmembrane conductance regulator mRNA with acute respiratory distress syndrome in children with pneumonia

Abstract Background Previous work has demonstrated a strong association between lung injury in African American children with pneumonia and a polymorphic (TG)mTn region in cystic fibrosis transmembrane conductance (CFTR) involved in the generation of a nonfunctional CFTR protein lacking exon 9. A number of splicing factors that regulate the inclusion/exclusion of exon 9 have been identified. The objective of this study was to determine whether genetic variants in these splicing factors were associated with acute respiratory distress syndrome (ARDS) in children with pneumonia. Methods This is a prospective cohort genetic association study of lung injury in African American and non-Hispanic Caucasian children with community-acquired pneumonia evaluated in the emergency department or admitted to the hospital. Linkage-disequilibrium-tag single nucleotide polymorphisms (LD-tag SNPs) in genes of the following splicing factors (followed by gene name) involved in exon 9 skipping PTB1 (PTBP1), SRp40 (SFRS1), SR2/ASF (SFRS5), TDP-43 (TARDBP), TIA-1 (TIA1), and U2AF65 (U2AF2) were genotyped. SNPs in the gene of the splicing factor CELF2 (CELF2) were selected by conservation score. Multivariable analysis was used to examine association between genotypes and ARDS. Results The African American cohort (n = 474) had 29 children with ARDS and the non-Hispanic Caucasian cohort (n = 304) had 32 children with ARDS. In the African American group multivariable analysis indicated that three variants in CELF2, rs7068124 (p = 0.004), rs3814634 (p = 0.032) and rs10905928 (p = 0.044), and two in TIA1, rs2592178 (p = 0.005) and rs13402990 (p = 0.018) were independently associated with ARDS. In the non-Hispanic Caucasian group, a single variant in CELF2, rs2277212 (p = 0.014), was associated with increased risk of developing ARDS. Conclusions The data indicate that SNPs in CELF2 may be associated with the risk of developing ARDS in both African American and non-Hispanic Caucasian children with pneumonia and suggest that the potential role of the splicing factor CELF2 in ARDS should be explored further.http://deepblue.lib.umich.edu/bitstream/2027.42/134745/1/13054_2016_Article_1454.pd

A multi-tissue age prediction model based on DNA methylation analysis

Age related tissue-specific DNA methylation markers have been identified in many studies, which can be used to estimate the chronological age of an unknown biological sample’s donor. However, if these markers have been used on the wrong type of tissue, they will give an inaccurate age estimation. This research has therefore examined HumanMethylation450 (HM450) BeadChip-based profiles retrieved from the NCBI repository, with the aim of identifying a set of universal DNA methylation markers across forensically relevant tissues. By using elastic net regression, it was possible to identify 10 age-related (AR) DNA methylation markers across 41 samples coming from five types of tissue (whole blood, saliva, semen, menstrual blood, and vaginal secretions). The average predictive accuracy of the constructed model based on training data is 3.8 years. In an independent dataset of 24 samples from four types of tissues (blood, saliva, menstrual blood, and vaginal secretions), the mean absolute deviation for the menstrual blood and vaginal fluid is 6.9 years, 5.6 years for buccal swabs, and 7.8 years for blood. The overall multi-tissue accuracy rate based on bootstrap analysis was 7.8 years (95% Confidence Interval 6–9.7 years). The identified multi-tissue age prediction model has the potential to assist forensic investigations without the requirement to identify the sample body fluid type

CT colonography polyp matching: differences between experienced readers

The purpose of this study was to investigate if experienced readers differ when matching polyps shown by both CT colonography (CTC) and optical colonoscopy (OC) and to explore the reasons for discrepancy. Twenty-eight CTC cases with corresponding OC were presented to eight experienced CTC readers. Cases represented a broad spectrum of findings, not completely fulfilling typical matching criteria. In 21 cases there was a single polyp on CTC and OC; in seven there were multiple polyps. Agreement between readers for matching was analyzed. For the 21 single-polyp cases, the number of correct matches per reader varied from 13 to 19. Almost complete agreement between readers was observed in 15 cases (71%), but substantial discrepancy was found for the remaining six (29%) probably due to large perceived differences in polyp size between CT and OC. Readers were able to match between 27 (71%) and 35 (92%) of the 38 CTC detected polyps in the seven cases with multiple polyps. Experienced CTC readers agree to a considerable extent when matching polyps between CTC and subsequent OC, but non-negligible disagreement exist