58 research outputs found
Incomplete quality of life data in lung transplant research: comparing cross sectional, repeated measures ANOVA, and multi-level analysis
BACKGROUND: In longitudinal studies on Health Related Quality of Life (HRQL) it frequently occurs that patients have one or more missing forms, which may cause bias, and reduce the sample size. Aims of the present study were to address the problem of missing data in the field of lung transplantation (LgTX) and HRQL, to compare results obtained with different methods of analysis, and to show the value of each type of statistical method used to summarize data. METHODS: Results from cross-sectional analysis, repeated measures on complete cases (ANOVA), and a multi-level analysis were compared. The scores on the dimension 'energy' of the Nottingham Health Profile (NHP) after transplantation were used to illustrate the differences between methods. RESULTS: Compared to repeated measures ANOVA, the cross-sectional and multi-level analysis included more patients, and allowed for a longer period of follow-up. In contrast to the cross sectional analyses, in the complete case analysis, and the multi-level analysis, the correlation between different time points was taken into account. Patterns over time of the three methods were comparable. In general, results from repeated measures ANOVA showed the most favorable energy scores, and results from the multi-level analysis the least favorable. Due to the separate subgroups per time point in the cross-sectional analysis, and the relatively small number of patients in the repeated measures ANOVA, inclusion of predictors was only possible in the multi-level analysis. CONCLUSION: Results obtained with the various methods of analysis differed, indicating some reduction of bias took place. Multi-level analysis is a useful approach to study changes over time in a data set where missing data, to reduce bias, make efficient use of available data, and to include predictors, in studies concerning the effects of LgTX on HRQL
Endovascular treatment of popliteal artery aneurysms: Results of a prospective cohort study
ObjectivePopliteal artery aneurysms can be treated endovascularly with less perioperative morbidity compared with open repair. To evaluate suitability of the endovascular technique and the clinical results of this treatment, we analyzed a prospective cohort of consecutive popliteal aneurysms referred to a tertiary university vascular center.MethodsAll popliteal artery aneurysms between June 1998 and June 2004 that measured >20 mm in diameter were analyzed for endovascular repair. Anatomic suitability was based largely on quality of the proximal and distal landing zone as determined by angiography. Endovascular treatment was performed by using a nitinol-supported expanded polytetrafluoroethylene lined stent graft introduced through the common femoral artery.ResultsWe analyzed 67 aneurysms in 57 patients. Ten aneurysms (15%) were excluded from endovascular repair, or from any repair at all, for various reasons. The remaining 57 (85%) were treated endovascularly, of which 5 were treated emergently for acute ischemia. During a mean 24-month follow-up, 12 stent grafts (21%) occluded. Primary and secondary patency rates were 80% and 90% at 1 year, and 77% and 87% at 2 years of follow-up. Postoperative treatment with clopidogrel proved to be the only significant predictor for success.ConclusionsEndovascular repair of a popliteal artery aneurysm is feasible. Changes in the material used and the addition of clopidogrel may improve patency rates
4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer
Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity in complex tumor tissue was reduced using laser capture microdissection (LCM). In the current study, we performed high resolution proteomic analysis on two cohorts of ER positive breast tumors derived from patients who either manifested good or poor outcome to tamoxifen treatment upon recurrence. A total of 112 fresh frozen tumors were collected from multiple medical centers and divided into two sets: an in-house training and a multi-center test set. Epithelial tumor cells were enriched with LCM and analyzed by nano-LC Orbitrap mass spectrometry (MS), which yielded >3000 and >4000 quantified proteins in the training and test sets, respectively. Raw data are available via ProteomeXchange with identifiers PXD000484 and PXD000485. Statistical analysis showed differential abundance of 99 proteins, of which a subset of 4 proteins was selected through a multivariate step-down to develop a predictor for tamoxifen treatment outcome. The 4-protein signature significantly predicted poor outcome patients in the test set, independent of predictive histopathological characteristics (hazard ratio [HR] = 2.17; 95% confidence interval [CI] = 1.15 to 4.17; multivariate Cox regression p value = 0.017). Immunohistochemical (IHC) staining of PDCD4, one of the signature proteins, on an independent set of formalin-fixed paraffin-embedded tumor tissues provided and independent technical validation (HR = 0.72; 95% CI = 0.57 to 0.92; multivariate Cox regression p value = 0.009). We hereby report the first validated protein predictor for tamoxifen treatment outcome in recurrent ER-positive breast cancer. IHC further showed that PDCD4 is an independent marker
Efficacy and safety of avapritinib in advanced systemic mastocytosis:interim analysis of the phase 2 PATHFINDER trial
Advanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase 2 trial (no. NCT03580655) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200 mg in patients with AdvSM (n = 62). The primary endpoint was overall response rate (ORR). Secondary endpoints included mean baseline change in AdvSM–Symptom Assessment Form Total Symptom Score and quality of life, time to response, duration of response, progression-free survival, overall survival, changes in measures of disease burden and safety. The primary endpoint was successfully met (P = 1.6 × 10(-9)), with an ORR of 75% (95% confidence interval 57–89) in 32 response-evaluable patients with AdvSM who had sufficient follow-up for response assessment, including 19% with complete remission with full or partial hematologic recovery. Reductions of ≥50% from baseline in serum tryptase (93%), bone marrow mast cells (88%) and KIT D816V variant allele fraction (60%) were observed. The most frequent grade ≥3 adverse events were neutropenia (24%), thrombocytopenia (16%) and anemia (16%). Avapritinib demonstrated a high rate of clinical, morphological and molecular responses and was generally well tolerated in patients with AdvSM
Identification of inhibitors that target dual-specificity phosphatase 5 provide new insights into the binding requirements for the two phosphate pockets
Methane Adsorption on Shale under Simulated Geological Temperature and Pressure Conditions
Protein expression, characterization and activity comparisons of wild type and mutant DUSP5 proteins
High-Pressure Methane Adsorption and Characterization of Pores in Posidonia Shales and Isolated Kerogens
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
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