SpaSM: A MATLAB Toolbox for Sparse Statistical Modeling

Applications in biotechnology such as gene expression analysis and image processing have led to a tremendous development of statistical methods with emphasis on reliable solutions to severely underdetermined systems. Furthermore, interpretations of such solutions are of importance, meaning that the surplus of inputs has been reduced to a concise model. At the core of this development are methods which augment the standard linear models for regression, classification and decomposition such that sparse solutions are obtained. This toolbox aims at making public available carefully implemented and well-tested variants of the most popular of such methods for the MATLAB programming environment. These methods consist of easy-to-read yet efficient implementations of various coefficient-path following algorithms and implementations of sparse principal component analysis and sparse discriminant analysis which are not available in MATLAB. The toolbox builds on code made public in 2005 and which has since been used in several studies

The impact of tumour size on the probability of synchronous metastasis and survival in renal cell carcinoma patients: a population-based study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The observed low metastatic potential and favorable survival of small incidentally detected renal cell carcinomas (RCCs) have been a part of the rationale for recommending partial nephrectomy as a first treatment option and active surveillance in selected patients. We examined the relationship between tumor size and the odds of synchronous metastases (SMs) (primary outcome) and disease specific survival (secondary outcome) in a nationwide RCC registry.Retrospective study of the 794 RCC patients diagnosed in Iceland between 1971 and 2005. Histological material and TNM staging were reviewed centrally. The presence of SM and survival were recorded. Cubic spline analysis was used to assess relationship between tumor size and probability of SM. Univariate and multivariate statistics were used to estimate prognostic factors for SM and survival.The probability of SM increased in a non-linear fashion with increasing tumor size (11, 25, 35, and 50%) for patients with tumors of ≤4, 4.1-7.0, 7.1-10.0, and >10 cm, respectively. On multivariate analysis, tumor size was an independent prognostic factor for disease-specific survival (HR = 1.05, 95% CI 1.02-1.09, p < 0.001), but not for SM.Tumor size affected the probability of disease-specific mortality but not SM, after correcting for TNM staging in multivariate analysis. This confirms the prognostic ability of the 2010 TNM staging system for renal cell cancer in the Icelandic population.Landspitali University Hospital Scientific Foundation Memorial Foundation of Bergthora Magnusdottir and Jakob J. Bjarnaso

Erratum: The impact of tumour size on the probability of synchronous metastasis and survival in renal cell carcinoma patients: a population-based study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access

Genetic correction of PSA values using sequence variants associated with PSA levels

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldMeasuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.info:eu-repo/grantAgreement/EC/FP7/202059/ 218071 Urological Research Foundation P50 CA90386-05S2 Robert H. Lurie Comprehensive Cancer Center p30 CA60553 Health Technology Assessment Programme 96/20/06 96/20/99 Department of Health, England Cancer Research UK C522/A8649 Medical Research Council of England G0500966 ID 75466 National Cancer Research Institute (NCRI), UK Southwest National Health Service Research and Development NCRI National Institute for Health Resear

Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Transcriptional and splicing anomalies have been observed in intron 8 of the CASP8 gene (encoding procaspase-8) in association with cutaneous basal-cell carcinoma (BCC) and linked to a germline SNP rs700635. Here, we show that the rs700635[C] allele, which is associated with increased risk of BCC and breast cancer, is protective against prostate cancer [odds ratio (OR) = 0.91, P = 1.0 × 10(-6)]. rs700635[C] is also associated with failures to correctly splice out CASP8 intron 8 in breast and prostate tumours and in corresponding normal tissues. Investigation of rs700635[C] carriers revealed that they have a human-specific short interspersed element-variable number of tandem repeat-Alu (SINE-VNTR-Alu), subfamily-E retrotransposon (SVA-E) inserted into CASP8 intron 8. The SVA-E shows evidence of prior activity, because it has transduced some CASP8 sequences during subsequent retrotransposition events. Whole-genome sequence (WGS) data were used to tag the SVA-E with a surrogate SNP rs1035142[T] (r(2) = 0.999), which showed associations with both the splicing anomalies (P = 6.5 × 10(-32)) and with protection against prostate cancer (OR = 0.91, P = 3.8 × 10(-7)).National Cancer Research Institute (NCRI) G0500966/75466 Department of Health, Medical Research Council Cancer Research UK University of Cambridge NIHR Department of Health Anniversary Fund of the Austrian National Bank 15079 Medical and Scientific Fund of the Mayor of the City of Vienna 10077 Common Fund of the Office of the Director of the National Institutes of Health NCI NHGRI NHLBI NIDA NIMH NINDS NCI\SAIC-Frederick, Inc. (SAIC-F) 10XS170 Roswell Park Cancer Institute 10XS171 Science Care, Inc. X10S172 SAIC-F 10ST1035 HHSN261200800001E deCODE genetics/AMGEN HHSN268201000029C DA006227 DA033684 N01MH000028 MH090941 MH101814 MH090951 MH090937 MH101820 MH101825 MH090936 MH101819 MH090948 MH101782 MH101810 MH10182

Gradual caldera collapse at Bárdarbunga volcano, Iceland, regulated by lateral magma outflow

Large volcanic eruptions on Earth commonly occur with a collapse of the roof of a crustal magma reservoir, forming a caldera. Only a few such collapses occur per century, and the lack of detailed observations has obscured insight into the mechanical interplay between collapse and eruption.We usemultiparameter geophysical and geochemical data to show that the 110-squarekilometer and 65-meter-deep collapse of Bárdarbunga caldera in 2014-2015 was initiated through withdrawal of magma, and lateral migration through a 48-kilometers-long dike, from a 12-kilometers deep reservoir. Interaction between the pressure exerted by the subsiding reservoir roof and the physical properties of the subsurface flow path explain the gradual, nearexponential decline of both collapse rate and the intensity of the 180-day-long eruption.</p