Survival and Decision-Making in Patients Turned Down for Abdominal Aortic Aneurysm Repair: A Retrospective Study with Focus on COVID-19 Impact.

OBJECTIVES: To investigate and analyse various aspects related to patients who have been placed on a "turn-down list" for elective or emergency repair of abdominal aortic aneurysms (AAA). METHODS: This retrospective study analysed data from the Black Country Vascular Network (BCVN). Multidisciplinary team (MDT) meetings assessed AAA patients referred through National Abdominal Aortic Aneurysm Screening Programme (NAAASP)or directly to vascular surgery. Patients considered unfit for intervention were added to a prospectively kept turndown list. Survival and cause of death data were collected, along with cardiopulmonary exercise testing (CPET) results and British Aneurysm Repair (BAR) scores for some patients. The study covered a period from January 2015 to May 2023. RESULTS: After exclusions 247 (16%) patients were placed on the turndown list with a median age of 85 years (IQR 8 years). The mortality of turndown cases on medical grounds was 74.1%. Survival was significantly higher for patients who completed CPET before being turned down (p = 0.004). Gender analysis revealed a higher proportion of females being turned down compared to males (p = 0.044). COVID-19 led to a notable reduction in the number of discussed cases and interventions, while the turndown rates remained consistent. Survival at one year in turndown patients was 66%, at three it was 29%, at four years it was18% and at 7 years it was 5%. Most patients whose cause of death was known died of respiratory complications (30%) or malignancy (19%). BAR scores and aneurysm size were not significant predictors of mortality. CONCLUSION: Patients on the turndown list have a substantial mortality rate. A significant proportion of female patients were being turned down compared to men and the reasons for this are not clear. Patients who completed CPET before being turned down had a longer survival time. While COVID-19 impacted healthcare services reducing the number of interventions, it did not influence turndown decisions. The study showed that the cause of death for a significant number of patients was respiratory complications or malignancy.

Shifts in isoform usage underlie transcriptional differences in regulatory T cells in type 1 diabetes.

Genome-wide association studies have identified numerous loci with allelic associations to Type 1 Diabetes (T1D) risk. Most disease-associated variants are enriched in regulatory sequences active in lymphoid cell types, suggesting that lymphocyte gene expression is altered in T1D. Here we assay gene expression between T1D cases and healthy controls in two autoimmunity-relevant lymphocyte cell types, memory CD4+/CD25+ regulatory T cells (Treg) and memory CD4+/CD25- T cells, using a splicing event-based approach to characterize tissue-specific transcriptomes. Limited differences in isoform usage between T1D cases and controls are observed in memory CD4+/CD25- T-cells. In Tregs, 402 genes demonstrate differences in isoform usage between cases and controls, particularly RNA recognition and splicing factor genes. Many of these genes are regulated by the variable inclusion of exons that can trigger nonsense mediated decay. Our results suggest that dysregulation of gene expression, through shifts in alternative splicing in Tregs, contributes to T1D pathophysiology.

UBASH3A Interacts with PTPN22 to Regulate IL2 Expression and Risk for Type 1 Diabetes.

UBASH3A is a negative regulator of T cell activation and IL-2 production and plays key roles in autoimmunity. Although previous studies revealed the individual effects of UBASH3A on risk for type 1 diabetes (T1D; a common autoimmune disease), the relationship of UBASH3A with other T1D risk factors remains largely unknown. Given that another well-known T1D risk factor, PTPN22, also inhibits T cell activation and IL-2 production, we investigated the relationship between UBASH3A and PTPN22. We found that UBASH3A, via its Src homology 3 (SH3) domain, physically interacts with PTPN22 in T cells, and that this interaction is not altered by the T1D risk coding variant rs2476601 in PTPN22. Furthermore, our analysis of RNA-seq data from T1D cases showed that the amounts of UBASH3A and PTPN22 transcripts exert a cooperative effect on IL2 expression in human primary CD8+ T cells. Finally, our genetic association analyses revealed that two independent T1D risk variants, rs11203203 in UBASH3A and rs2476601 in PTPN22, interact statistically, jointly affecting risk for T1D. In summary, our study reveals novel interactions, both biochemical and statistical, between two independent T1D risk loci, and suggests how these interactions may affect T cell function and increase risk for T1D.

Sex-Biased Expression Is Associated With Chromatin State in Drosophila melanogaster and Drosophila simulans.

In Drosophila melanogaster and D. simulans head tissue, 60% of orthologous genes show evidence of sex-biased expression in at least one species. Of these, ∼39% (2,192) are conserved in direction. We hypothesize enrichment of open chromatin in the sex where we see expression bias and closed chromatin in the opposite sex. Male-biased orthologs are significantly enriched for H3K4me3 marks in males of both species (∼89% of male-biased orthologs vs. ∼76% of unbiased orthologs). Similarly, female-biased orthologs are significantly enriched for H3K4me3 marks in females of both species (∼90% of female-biased orthologs vs. ∼73% of unbiased orthologs). The sex-bias ratio in female-biased orthologs was similar in magnitude between the two species, regardless of the closed chromatin (H3K27me2me3) marks in males. However, in male-biased orthologs, the presence of H3K27me2me3 in both species significantly reduced the correlation between D. melanogaster sex-bias ratio and the D. simulans sex-bias ratio. Male-biased orthologs are enriched for evidence of positive selection in the D. melanogaster group. There are more male-biased genes than female-biased genes in both species. For orthologs with gains/losses of sex-bias between the two species, there is an excess of male-bias compared to female-bias, but there is no consistent pattern in the relationship between H3K4me3 or H3K27me2me3 chromatin marks and expression. These data suggest chromatin state is a component of the maintenance of sex-biased expression and divergence of sex-bias between species is reflected in the complexity of the chromatin status.

Sex-biased expression is associated with chromatin state in D. melanogaster and D. simulans.

We propose a new model for the association of chromatin state and sex-bias in expression. We hypothesize enrichment of open chromatin in the sex where we see expression bias (OS) and closed chromatin in the opposite sex (CO). In this study of D. melanogaster and D. simulans head tissue, sex-bias in expression is associated with H3K4me3 (open mark) in males for male-biased genes and in females for female-biased genes in both species. Sex-bias in expression is also largely conserved in direction and magnitude between the two species on the X and autosomes. In male-biased orthologs, the sex-bias ratio is more divergent between species if both species have H3K27me2me3 marks in females compared to when either or neither species has H3K27me2me3 in females. H3K27me2me3 marks in females are associated with male-bias in expression on the autosomes in both species, but on the X only in D. melanogaster . In female-biased orthologs the relationship between the species for the sex-bias ratio is similar regardless of the H3K27me2me3 marks in males. Female-biased orthologs are more similar in the ratio of sex-bias than male-biased orthologs and there is an excess of male-bias in expression in orthologs that gain/lose sex-bias. There is an excess of male-bias in sex-limited expression in both species suggesting excess male-bias is due to rapid evolution between the species. The X chromosome has an enrichment in male-limited H3K4me3 in both species and an enrichment of sex-bias in expression compared to the autosomes.

Variation in leaf transcriptome responses to elevated ozone corresponds with physiological sensitivity to ozone across maize inbred lines.

We examine the impact of sustained elevated ozone concentration on the leaf transcriptome of 5 diverse maize inbred genotypes, which vary in physiological sensitivity to ozone (B73, Mo17, Hp301, C123, and NC338), using long reads to assemble transcripts and short reads to quantify expression of these transcripts. More than 99% of the long reads, 99% of the assembled transcripts, and 97% of the short reads map to both B73 and Mo17 reference genomes. Approximately 95% of the genes with assembled transcripts belong to known B73-Mo17 syntenic loci and 94% of genes with assembled transcripts are present in all temperate lines in the nested association mapping pan-genome. While there is limited evidence for alternative splicing in response to ozone stress, there is a difference in the magnitude of differential expression among the 5 genotypes. The transcriptional response to sustained ozone stress in the ozone resistant B73 genotype (151 genes) was modest, while more than 3,300 genes were significantly differentially expressed in the more sensitive NC338 genotype. There is the potential for tandem duplication in 30% of genes with assembled transcripts, but there is no obvious association between potential tandem duplication and differential expression. Genes with a common response across the 5 genotypes (83 genes) were associated with photosynthesis, in particular photosystem I. The functional annotation of genes not differentially expressed in B73 but responsive in the other 4 genotypes (789) identifies reactive oxygen species. This suggests that B73 has a different response to long-term ozone exposure than the other 4 genotypes. The relative magnitude of the genotypic response to ozone, and the enrichment analyses are consistent regardless of whether aligning short reads to: long read assembled transcripts; the B73 reference; the Mo17 reference. We find that prolonged ozone exposure directly impacts the photosynthetic machinery of the leaf.

Genetic Control of Splicing at SIRPG Modulates Risk of Type 1 Diabetes.

Signal regulatory protein SIRPγ (CD172G) is expressed on the surface of lymphocytes, where it acts by engaging its ligand, CD47. SIRPG, which encodes SIRPγ, contains a nonsynonymous coding variant, rs6043409, which is significantly associated with risk for type 1 diabetes. SIRPG produces multiple transcript isoforms via alternative splicing, all encoding potentially functional proteins. We show that rs6043409 alters a predicted exonic splicing enhancer, resulting in significant shifts in the distribution of SIRPG transcript isoforms. All of these transcript isoforms produced protein upon transient expression in vitro. However, CRISPR/Cas9 targeting of one of the alternatively spliced exons in SIRPG eliminated all SIRPγ expression in Jurkat T cells. These targeted cells formed fewer cell-cell conjugates with each other than with wild-type Jurkat cells, expressed reduced levels of genes associated with CD47 signaling, and had significantly increased levels of cell-surface CD47. In primary CD4+ and CD8+ T cells, cell-surface SIRPγ levels in response to anti-CD3 stimulation varied quantitatively by rs6043409 genotype. Our results suggest that SIRPG is the most likely causative gene for type 1 diabetes risk in the 20p13 region and highlight the role of alternative splicing in lymphocytes in mediating the genetic risk for autoimmunity.

Testcrosses are an efficient strategy for identifying cis-regulatory variation: Bayesian analysis of allele-specific expression (BayesASE).

Allelic imbalance (AI) occurs when alleles in a diploid individual are differentially expressed and indicates cis acting regulatory variation. What is the distribution of allelic effects in a natural population? Are all alleles the same? Are all alleles distinct? The approach described applies to any technology generating allele-specific sequence counts, for example for chromatin accessibility and can be applied generally including to comparisons between tissues or environments for the same genotype. Tests of allelic effect are generally performed by crossing individuals and comparing expression between alleles directly in the F1. However, a crossing scheme that compares alleles pairwise is a prohibitive cost for more than a handful of alleles as the number of crosses is at least (n2-n)/2 where n is the number of alleles. We show here that a testcross design followed by a hypothesis test of AI between testcrosses can be used to infer differences between nontester alleles, allowing n alleles to be compared with n crosses. Using a mouse data set where both testcrosses and direct comparisons have been performed, we show that the predicted differences between nontester alleles are validated at levels of over 90% when a parent-of-origin effect is present and of 60%-80% overall. Power considerations for a testcross, are similar to those in a reciprocal cross. In all applications, the testing for AI involves several complex bioinformatics steps. BayesASE is a complete bioinformatics pipeline that incorporates state-of-the-art error reduction techniques and a flexible Bayesian approach to estimating AI and formally comparing levels of AI between conditions. The modular structure of BayesASE has been packaged in Galaxy, made available in Nextflow and as a collection of scripts for the SLURM workload manager on github (https://github.com/McIntyre-Lab/BayesASE).

tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing.

Recent advances in long-read sequencing solve inaccuracies in alternative transcript identification of full-length transcripts in short-read RNA-Seq data, which encourages the development of methods for isoform-centered functional analysis. Here, we present tappAS, the first framework to enable a comprehensive Functional Iso-Transcriptomics (FIT) analysis, which is effective at revealing the functional impact of context-specific post-transcriptional regulation. tappAS uses isoform-resolved annotation of coding and non-coding functional domains, motifs, and sites, in combination with novel analysis methods to interrogate different aspects of the functional readout of transcript variants and isoform regulation. tappAS software and documentation are available at https://app.tappas.org.

Meta-analysis of direct surgical versus endovascular revascularization for aortoiliac occlusive disease.

OBJECTIVE: There is a paucity of good-quality evidence comparing direct surgical (DS) with endovascular/hybrid (EVH) revascularization for aortoiliac occlusive disease (AIOD). We aimed to perform a meta-analysis of studies comparing DS and EVH revascularization for AIOD. METHODS: PubMed, Ovid MEDLINE, Cochrane, and Embase databases were searched for studies comparing DS and EVH revascularization for AIOD from 2000 to 2018. Risk of bias assessment was performed using the Methodological Index for Non-Randomized Studies. Demographics, clinical presentation, and comorbidities of the two groups were compared. Kaplan-Meier curves from selected studies were digitized with WebPlotDigitizer. Meta-analysis was conducted using Review Manager, and outcome measures were compared. Subgroup analysis was performed for primary patency in the EVH group. RESULTS: Eleven observational studies were identified comparing a sample of 4030 patients. The median Methodological Index for Non-Randomized Studies score was 19 of 24. A total of 1679 and 2351 patients underwent DS and EVH techniques, respectively. No significant difference was found between means for sex, claudication, rest pain, tissue loss, preoperative ankle-brachial pressure index, and TransAtlantic Inter-Society Consensus C and D lesions in the two groups averaged across studies. However, the DS group had significantly younger patients (average age, 61.83 vs 66.77; P = .0011). The risk factors of the two groups, such as smoking, diabetes, ischemic heart disease, hypertension, hyperlipidemia, renal failure, and chronic lung disease, were comparable. Average hospital stay was significantly higher for the DS group (7.76 days vs 3.12 days; P = .025). Change in ankle-brachial pressure index, 30-day mortality, and 30-day graft/stent thrombosis were not significantly different for the groups. Overall, primary patency for a median follow-up of 50 months favored the DS group (hazard ratio [HR], 0.51; confidence interval [CI], 0.36-0.73; P = .0002). There was moderate heterogeneity among studies (I2 = 46%). The HR for the subgroup for which endovascular procedures were combined with common femoral endarterectomy was 0.43 compared with 0.88 for endovascular revascularization alone. Limb salvage was similar in both groups (HR, 1.10; CI, 0.74-1.64; P = .63), but overall survival after the procedure favored the DS group (HR, 0.75; CI, 0.60-0.94; P = .01; I2 = 0%). CONCLUSIONS: Moderate-quality studies showed that DS revascularization had significantly better primary patency than EVH revascularization for AIOD, although DS patients were younger and may have differed on other confounding variables. Both techniques had similar limb salvage rates, and the primary patency was better for endovascular revascularization combined with common femoral endarterectomy than for endovascular revascularization alone.

A Randomised Controlled Trial Comparing Three Different Radiofrequency Technologies: Short-Term Results of the 3-RF Trial.

OBJECTIVE: To date there has been no comparison of outcomes of endovenous radiofrequency (RF) devices. The 3-RF trial is the first randomised controlled trial of three commercially available RF ablation technologies. METHODS: Patients were recruited [182/302 patients with great saphenous vein (GSV) incompetence] into a prospective double blind randomised trial of Venefit, radiofrequency induced thermal therapy (RFITT), and endovenous radiofrequency (EVRF). The primary outcome measure was GSV closure (total/partial/failed) at six months. Secondary outcome measures included ablation times, complications, pain scores, analgesia requirements, and quality of life (QoL) scores to 12 months. RESULTS: Patients treated [180: Venefit (57), RFITT (64), EVRF (59)] were matched for age, sex, and vein characteristics. At six months, complete GSV closure was significantly better after Venefit and RFITT treatment (100% and 98%, respectively) compared with EVRF treatment (79%, p < .001). Mean treatment time was significantly faster for RFITT than for Venefit and EVRF (p < .0001). Euroqol 5D (EQ5D) visual analogue score (VAS) did not differ between groups at any time point. The only difference between groups in EQ5D domain scores was for the pain/discomfort domain at two weeks when significantly fewer EVRF patients reported no problems compared with Venefit and RFITT. This difference had disappeared at six and 12 months. The Aberdeen Varicose Vein Questionnaire (AVVQ) improved for all groups at six and 12 months compared with pre-treatment levels; however, there was no significant difference between groups. CONCLUSION: Compared with Venefit and RFITT, EVRF was associated with significant failure of truncal ablation at six months; however, clinical outcomes did not differ significantly at 12 months. clinicaltrials.gov identifier: NCT02441881, NHS Health Research Authority (Hampstead Research Ethics Committee) number: 14/LO/1232.

Artery Ligation for Infected Femoral Pseudoaneurysms Does Carry a High Risk of Major Amputation.

BACKGROUND: Arterial ligation has been described in the literature as a safe and effective procedure with a relatively low number of patients requiring major amputations. METHODS: We performed a retrospective analysis of a prospectively held database of all patients who underwent arterial ligation for infected femoral pseudoaneurysms due to chronic intravenous drug abuse from January 2012 to March 2018. Information recorded for each patient included age, gender, blood investigations, microbiologic results, diagnostic modality, operative details, outcome of surgery, postoperative complications, and follow-up. RESULTS: There were 25 patients identified, with 2 of them undergoing bilateral ligations. It was more common in men (4:1), and the mean age at presentation was 39.7 years (standard deviation 8.2 y). Nine patients underwent major limb amputation for severe limb ischemia (7 transfemoral amputations and two 53 hip disarticulation). Average hospital stay was 24 days, and there was no mortality. We found a trend with a higher level of arterial ligation, leading to a higher rate of amputation. CONCLUSIONS: Our study is the first to show that there is a trend toward a higher risk of amputation with a higher level of ligation in this cohort of patients, and therefore, we suggest avoidance of external iliac artery ligation even at the most distal part just under the ligament, leaving the circumflex iliac vessel in circuit. Arterial ligation also carries a higher risk of major amputation than previously reported.

Short-term Mortality, Morbidity and Recovery Milestones after Major Lower Limb Amputation: a Prospective Evaluation of Outcomes in a Tertiary Center.

BACKGROUND: Major lower limb amputation (MLLA) is well recognized to carry a high rate of mortality; however, little evidence explores the reasons for this. Even fewer studies look at other outcomes after MLLA such as major morbidity and functional and social recovery. This study aims to provide a contemporary analysis of these outcomes to contextualize the current state of care for MLLA in the United Kingdom. METHODS: All index MLLAs conducted in a single tertiary vascular center over a 1-year period were entered into the study. Data including demographic details, preoperative biochemical markers, and functional and social status were collected by a multidisciplinary team . Postoperative functional recovery milestones, and mortality and major morbidity data were collected prospectively from the date of amputation. Descriptive, univariate and multivariate analysis was used to present the results. RESULTS: Seventy-nine amputations were performed. The median total length of stay was 28.0 days (interquartile range [IQR] 14.0-48.0), and postoperative length was 18.0 days (IQR 9.5-36.0). Thirty-day mortality was 5.1% (n = 4), and 90-day mortality was 8.9% (n = 7). Thirty-day major morbidity was 32.4% (n = 24). After controlling for age and gender, preoperative serum white cell count was an independent predictor of 30-day mortality (odds ratio [OR] 1.375 [95% confidence interval [CI] 1.080-1.751]), 90-day mortality (OR 1.258 [95% CI 1.078-1.469]), and 30-day major morbidity (OR 1.228 [95% CI 1.070-1.409]. The proportion of the population living independently reduced from 56.7% to 13.7%, with 23.3% requiring further rehabilitation. The number needing either social care at home or permanent care placement rose by 12.8%. CONCLUSIONS: MLLA carries clinically significant risk of short-term mortality and morbidity. The only factor found to be consistently influential was preoperative serum white cell count. MLLA requires a significant in-hospital stay, and there is a significant deterioration in functional and social status after discharge from hospital.

Amputation for osteomyelitis in a patient with spina bifida.

We describe a case of osteomyelitis in a patient with spina bifida presenting to the vascular surgeon and highlight the complex challenges encountered. We review the literature and demonstrate how good multidisciplinary care and early consideration for surgical amputation may benefit this unique group of patients.

Event Analysis: Using Transcript Events To Improve Estimates of Abundance in RNA-seq Data.

Alternative splicing leverages genomic content by allowing the synthesis of multiple transcripts and, by implication, protein isoforms, from a single gene. However, estimating the abundance of transcripts produced in a given tissue from short sequencing reads is difficult and can result in both the construction of transcripts that do not exist, and the failure to identify true transcripts. An alternative approach is to catalog the events that make up isoforms (splice junctions and exons). We present here the Event Analysis (EA) approach, where we project transcripts onto the genome and identify overlapping/unique regions and junctions. In addition, all possible logical junctions are assembled into a catalog. Transcripts are filtered before quantitation based on simple measures: the proportion of the events detected, and the coverage. We find that mapping to a junction catalog is more efficient at detecting novel junctions than mapping in a splice aware manner. We identify 99.8% of true transcripts while iReckon identifies 82% of the true transcripts and creates more transcripts not included in the simulation than were initially used in the simulation. Using PacBio Iso-seq data from a mouse neural progenitor cell model, EA detects 60% of the novel junctions that are combinations of existing exons while only 43% are detected by STAR. EA further detects ∼5,000 annotated junctions missed by STAR. Filtering transcripts based on the proportion of the transcript detected and the number of reads on average supporting that transcript captures 95% of the PacBio transcriptome. Filtering the reference transcriptome before quantitation, results in is a more stable estimate of isoform abundance, with improved correlation between replicates. This was particularly evident when EA is applied to an RNA-seq study of type 1 diabetes (T1D), where the coefficient of variation among subjects (n = 81) in the transcript abundance estimates was substantially reduced compared to the estimation using the full reference. EA focuses on individual transcriptional events. These events can be quantitate and analyzed directly or used to identify the probable set of expressed transcripts. Simple rules based on detected events and coverage used in filtering result in a dramatic improvement in isoform estimation without the use of ancillary data (e.g., ChIP, long reads) that may not be available for many studies.

Analysis of Gene Expression Variance in Schizophrenia Using Structural Equation Modeling.

Schizophrenia (SCZ) is a psychiatric disorder of unknown etiology. There is evidence suggesting that aberrations in neurodevelopment are a significant attribute of schizophrenia pathogenesis and progression. To identify biologically relevant molecular abnormalities affecting neurodevelopment in SCZ we used cultured neural progenitor cells derived from olfactory neuroepithelium (CNON cells). Here, we tested the hypothesis that variance in gene expression differs between individuals from SCZ and control groups. In CNON cells, variance in gene expression was significantly higher in SCZ samples in comparison with control samples. Variance in gene expression was enriched in five molecular pathways: serine biosynthesis, PI3K-Akt, MAPK, neurotrophin and focal adhesion. More than 14% of variance in disease status was explained within the logistic regression model (C-value = 0.70) by predictors accounting for gene expression in 69 genes from these five pathways. Structural equation modeling (SEM) was applied to explore how the structure of these five pathways was altered between SCZ patients and controls. Four out of five pathways showed differences in the estimated relationships among genes: between KRAS and NF1, and KRAS and SOS1 in the MAPK pathway; between PSPH and SHMT2 in serine biosynthesis; between AKT3 and TSC2 in the PI3K-Akt signaling pathway; and between CRK and RAPGEF1 in the focal adhesion pathway. Our analysis provides evidence that variance in gene expression is an important characteristic of SCZ, and SEM is a promising method for uncovering altered relationships between specific genes thus suggesting affected gene regulation associated with the disease. We identified altered gene-gene interactions in pathways enriched for genes with increased variance in expression in SCZ. These pathways and loci were previously implicated in SCZ, providing further support for the hypothesis that gene expression variance plays important role in the etiology of SCZ.

Variable selection in omics data: A practical evaluation of small sample sizes.

In omics experiments, variable selection involves a large number of metabolites/ genes and a small number of samples (the n < p problem). The ultimate goal is often the identification of one, or a few features that are different among conditions- a biomarker. Complicating biomarker identification, the p variables often contain a correlation structure due to the biology of the experiment making identifying causal compounds from correlated compounds difficult. Additionally, there may be elements in the experimental design (blocks, batches) that introduce structure in the data. While this problem has been discussed in the literature and various strategies proposed, the over fitting problems concomitant with such approaches are rarely acknowledged. Instead of viewing a single omics experiment as a definitive test for a biomarker, an unrealistic analytical goal, we propose to view such studies as screening studies where the goal of the study is to reduce the number of features present in the second round of testing, and to limit the Type II error. Using this perspective, the performance of LASSO, ridge regression and Elastic Net was compared with the performance of an ANOVA via a simulation study and two real data comparisons. Interestingly, a dramatic increase in the number of features had no effect on Type I error for the ANOVA approach. ANOVA, even without multiple test correction, has a low false positive rates in the scenarios tested. The Elastic Net has an inflated Type I error (from 10 to 50%) for small numbers of features which increases with sample size. The Type II error rate for the ANOVA is comparable or lower than that for the Elastic Net leading us to conclude that an ANOVA is an effective analytical tool for the initial screening of features in omics experiments.

The role of compression after endovenous ablation of varicose veins.

OBJECTIVE: The aim of this review was to identify the evidence regarding the optimal duration of compression therapy after endovenous ablation of varicose veins. METHODS: Electronic databases were searched for studies assessing the use of compression after endovenous ablation in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The primary outcomes for this study were pain score and complications. Secondary outcomes were time to full recovery, quality of life score, leg circumference, bruising score, and compliance rates. RESULTS: Following strict inclusion and exclusion criteria, five studies were included in our review, including a total of 734 patients. The short-duration compression therapy ranged from 4 hours to 2 days, whereas the longer duration ranged from 3 to 15 days. A single study showed a better outcome in terms of complications with a short compression therapy. A single study showed a benefit to pain and quality of life with extended compression therapy, whereas the others did not. There was no significant difference in terms of bruising, recovery time, and leg swelling. CONCLUSIONS: Our review showed that there is no evidence for the extended use of compression after endovenous ablation of varicose veins.

Prior Radiological Investigations in 65-Year-Old Men Screened for AAA.

BACKGROUND: The National Health Service abdominal aortic aneurysm screening programme (NAAASP) is now fully operational. Those who have previously been formally investigated for abdominal aortic aneurysm (AAA) are excluded; however, many patients undergo radiological investigation of the abdomen for other reasons. Such practices may find incidental AAA which may be eroding the performance of the NAAASP. We investigated the rates of preinvestigation before invitation to screening in our local AAA screening programme. METHODS: Electronic patient records were retrospectively reviewed for all patients called between March 2013 and February 2016 in 1 local AAA screening programme. Their records were interrogated to identify any abdominal imaging within 5 years of their invitation to screening. RESULTS: Two thousand six hundred thirty-eight men were invited for screening; of these, 563 (21.3%) had been "prescreened". Median time between prescreening and screening was 19 months (0-60 months). Ultrasound abdomen was the most prevalent at 248 (44.0%). Two thousand two hundred forty-three (85.0%) men attended screening, and 6 (0.27%) were excluded for known AAA. Prevalence of AAA was 1.8% (n = 41). Of these, 15 (36.6%) had prior investigation with 6 (40.0%) having AAA diagnosed. Therefore, 9 (22.0%) had potential missed AAA on "prescreening" (mean diameter 35 mm [30-45], mean time lapse between investigation and screening 21.1 months [1-49]). Incidence of missed aneurysm in the "prescreened" cohort was 1.6% (9/563). CONCLUSIONS: Large numbers of men invited for AAA screening have undergone preinvestigation of their abdominal aorta, with 60% of the present AAA being missed. Reliance on incidental detection of AAA would leave many patients undiagnosed in the community-at risk of future rupture.