Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in patients with elevated triglycerides (200-499 mg/dL) on statin therapy: Rationale and design of the EVAPORATE study.

Despite reducing progression and promoting regression of coronary atherosclerosis, statin therapy does not fully address residual cardiovascular (CV) risk. High-purity eicosapentaenoic acid (EPA) added to a statin has been shown to reduce CV events and induce regression of coronary atherosclerosis in imaging studies; however, data are from Japanese populations without high triglyceride (TG) levels and baseline EPA serum levels greater than those in North American populations. Icosapent ethyl is a high-purity prescription EPA ethyl ester approved at 4 g/d as an adjunct to diet to reduce TG levels in adults with TG levels >499 mg/dL. The objective of the randomized, double-blind, placebo-controlled EVAPORATE study is to evaluate the effects of icosapent ethyl 4 g/d on atherosclerotic plaque in a North American population of statin-treated patients with coronary atherosclerosis, TG levels of 200 to 499 mg/dL, and low-density lipoprotein cholesterol levels of 40 to 115 mg/dL. The primary endpoint is change in low-attenuation plaque volume measured by multidetector computed tomography angiography. Secondary endpoints include incident plaque rates; quantitative changes in different plaque types and morphology; changes in markers of inflammation, lipids, and lipoproteins; and the relationship between these changes and plaque burden and/or plaque vulnerability. Approximately 80 patients will be followed for 9 to 18 months. The clinical implications of icosapent ethyl 4 g/d treatment added to statin therapy on CV endpoints are being evaluated in the large CV outcomes study REDUCE-IT. EVAPORATE will provide important imaging-derived data that may add relevance to the clinically derived outcomes from REDUCE-IT

Making a Third Space for Student Voices in Two Academic Libraries

When we think of voices in the library, we have tended to think of them as disruptive, something to control and manage for the sake of the total library environment. The stereotype of the shushing librarian pervades public perception, creating expectations about the kinds of spaces libraries want to create. Voices are not always disruptive, however. Indeed, developing an academic voice is one of the main challenges facing incoming university students, and libraries can play an important role in helping these students find their academic voices. Two initiatives at two different academic libraries are explored here: a Secrets Wall, where students are invited to write and share a secret during exam time while seeing, reading, commenting on the secrets of others; and a librarian and historian team-taught course called History on the Web, which brings together information literacy and the study of history in the digital age. This article examines both projects and considers how critical perspectives on voice and identity might guide our instructional practices, helping students to learn to write themselves into the university. Further, it describes how both the Secrets Wall and the History on the Web projects intentionally create a kind of “Third Space” designed specifically so students can enter it, negotiate with it, interrogate it, and eventually come to be part of it

Reproducibility, stability, and accuracy of microbial profiles by fecal sample collection method in three distinct populations.

The gut microbiome likely plays a role in the etiology of multiple health conditions, especially those affecting the gastrointestinal tract. Little consensus exists as to the best, standard methods to collect fecal samples for future microbiome analysis. We evaluated three distinct populations (N = 132 participants) using 16S rRNA gene amplicon sequencing data to investigate the reproducibility, stability, and accuracy of microbial profiles in fecal samples collected and stored via fecal occult blood test (FOBT) or Flinders Technology Associates (FTA) cards, fecal immunochemical tests (FIT) tubes, 70% and 95% ethanol, RNAlater, or with no solution. For each collection method, based on relative abundance of select phyla and genera, two alpha diversity metrics, and four beta diversity metrics, we calculated intraclass correlation coefficients (ICCs) to estimate reproducibility and stability, and Spearman correlation coefficients (SCCs) to estimate accuracy of the fecal microbial profile. Comparing duplicate samples, reproducibility ICCs for all collection methods were excellent (ICCs ≥75%). After 4-7 days at ambient temperature, ICCs for microbial profile stability were excellent (≥75%) for most collection methods, except those collected via no-solution and 70% ethanol. SCCs comparing each collection method to immediately-frozen no-solution samples ranged from fair to excellent for most methods; however, accuracy of genus-level relative abundances differed by collection method. Our findings, taken together with previous studies and feasibility considerations, indicated that FOBT/FTA cards, FIT tubes, 95% ethanol, and RNAlater are excellent choices for fecal sample collection methods in future microbiome studies. Furthermore, establishing standard collection methods across studies is highly desirable

Capturing One of the Human Gut Microbiome's Most Wanted:Reconstructing the Genome of a Novel Butyrate-Producing, Clostridia! Scavenger from Metagenomic Sequence Data

The role of the microbiome in health and disease is attracting great attention, yet we still know little about some of the most prevalent microorganisms inside our bodies. Several years ago, Human Microbiome Project (HMP) researchers generated a list of “most wanted” taxa: bacteria both prevalent among healthy volunteers and distantly related to any sequenced organisms. Unfortunately, the challenge of assembling high-quality genomes from a tangle of metagenomic reads has slowed progress in learning about these uncultured bacteria. Here, we describe how recent advances in sequencing and analysis allowed us to assemble “most wanted” genomes from metagenomic data collected from four stool samples. Using a combination of both de novo and guided assembly methods, we assembled and binned over 100 genomes from an initial data set of over 1,300 Gbp. One of these genome bins, which met HMP’s criteria for a “most wanted” taxa, contained three essentially complete genomes belonging to a previously uncultivated species. This species is most closely related to Eubacterium desmolans and the clostridial cluster IV/Clostridium leptum subgroup species Butyricicoccus pullicaecorum (71–76% average nucleotide identity). Gene function analysis indicates that the species is an obligate anaerobe, forms spores, and produces the anti-inflammatory short-chain fatty acids acetate and butyrate. It also appears to take up metabolically costly molecules such as cobalamin, methionine, and branch-chained amino acids from the environment, and to lack virulence genes. Thus, the evidence is consistent with a secondary degrader that occupies a host-dependent, nutrient-scavenging niche within the gut; its ability to produce butyrate, which is thought to play an anti-inflammatory role, makes it intriguing for the study of diseases such as colon cancer and inflammatory bowel disease. In conclusion, we have assembled essentially complete genomes from stool metagenomic data, yielding valuable information about uncultured organisms’ metabolic and ecologic niches, factors that may be required to successfully culture these bacteria, and their role in maintaining health and causing disease

Boolean analysis identifies CD38 as a biomarker of aggressive localized prostate cancer.

The introduction of serum Prostate Specific Antigen (PSA) testing nearly 30 years ago has been associated with a significant shift towards localized disease and decreased deaths due to prostate cancer. Recognition that PSA testing has caused over diagnosis and over treatment of prostate cancer has generated considerable controversy over its value, and has spurred efforts to identify prognostic biomarkers to distinguish patients who need treatment from those that can be observed. Recent studies show that cancer is heterogeneous and forms a hierarchy of tumor cell populations. We developed a method of identifying prostate cancer differentiation states related to androgen signaling using Boolean logic. Using gene expression data, we identified two markers, CD38 and ARG2, that group prostate cancer into three differentiation states. Cancers with CD38-, ARG2- expression patterns, corresponding to an undifferentiated state, had significantly lower 10-year recurrence-free survival compared to the most differentiated group (CD38+ARG2+). We carried out immunohistochemical (IHC) staining for these two markers in a single institution (Stanford; n = 234) and multi-institution (Canary; n = 1326) cohorts. IHC staining for CD38 and ARG2 in the Stanford cohort demonstrated that combined expression of CD38 and ARG2 was prognostic. In the Canary cohort, low CD38 protein expression by IHC was significantly associated with recurrence-free survival (RFS), seminal vesicle invasion (SVI), extra-capsular extension (ECE) in univariable analysis. In multivariable analysis, ARG2 and CD38 IHC staining results were not independently associated with RFS, overall survival, or disease-specific survival after adjusting for other factors including SVI, ECE, Gleason score, pre-operative PSA, and surgical margins

南極内陸域における雲と放射の研究

Supplementary Methods. (PDF 686 kb

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations