Tephrostratigraphy and provenance from IODP Expedition 352, Izu-Bonin arc: tracing tephra sources and volumes from the Oligocene to the Recent

Provenance studies of widely distributed tephras, integrated within a well-defined temporal framework, are important to deduce systematic changes in the source, scale, distribution and changes in regional explosive volcanism. Here, we establish a robust tephro-chronostratigraphy for a total of 157 marine tephra layers collected during IODP Expedition 352. We infer at least three major phases of highly explosive volcanism during Oligocene to Pleistocene time. Provenance analysis based on glass composition assigns 56 of the tephras to a Japan source, including correlations with 12 major and widespread tephra layers resulting from individual eruptions in Kyushu, Central Japan and North Japan between 115 ka and 3.5 Ma. The remaining 101 tephras are assigned to four source regions along the Izu-Bonin arc. One, of exclusively Oligocene age, is proximal to the Bonin Ridge islands; two reflect eruptions within the volcanic front and back-arc of the central Izu-Bonin arc, and a fourth region corresponds to the Northern Izu-Bonin arc source. First-order volume estimates imply eruptive magnitudes ranging from 6.3 to 7.6 for Japan-related eruptions and between 5.5 and 6.5 for IBM eruptions. Our results suggest tephras between 30 and 22 Ma that show a subtly different Izu-Bonin chemical signature compared to the recent arc. After a ∼11 m.y. gap in eruption, tephra supply from the Izu-Bonin arc predominates from 15 to 5 Ma, and finally a subequal mixture of tephra sources from the (palaeo)Honshu and Izu-Bonin arcs occurs within the last ∼5 Ma

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Economics and Regulation of PRP in the Evolving Field of Orthopedic Biologics.

This review provides an update on the current status of platelet-rich plasma (PRP). Topics covered include the current regulatory environment, economic outlook, and current clinical evidence.The global PRP market is expected to grow to between 380 million and 4.5 billion (USD) over the next 5-10 years. The cost of a single treatment, which is not covered by most insurance, is roughly $500-$2500, with patients often returning for additional treatments. While PRP is not 'FDA-approved', it can be legally offered in the clinic 'off-label' in the USA for a myriad of musculoskeletal indications. Recently published meta-analyses have demonstrated statistically significant improvements that, in some cases, suggest that PRP may have clinically meaningful effects. However, given the fact that clearance is not synonymous with approval, PRP is a costly treatment not covered by insurance, and clinical trials have not demonstrated definitive efficacy, we recommend informing patients when providing PRP 'off-label'

The Economics and Regulation of PRP in the Evolving Field of Orthopedic Biologics.

This review provides an update on the current status of platelet-rich plasma (PRP). Topics covered include the current regulatory environment, economic outlook, and current clinical evidence.The global PRP market is expected to grow to between 380 million and 4.5 billion (USD) over the next 5-10 years. The cost of a single treatment, which is not covered by most insurance, is roughly $500-$2500, with patients often returning for additional treatments. While PRP is not 'FDA-approved', it can be legally offered in the clinic 'off-label' in the USA for a myriad of musculoskeletal indications. Recently published meta-analyses have demonstrated statistically significant improvements that, in some cases, suggest that PRP may have clinically meaningful effects. However, given the fact that clearance is not synonymous with approval, PRP is a costly treatment not covered by insurance, and clinical trials have not demonstrated definitive efficacy, we recommend informing patients when providing PRP 'off-label'

Anabolic steroids and tendons: A review of their mechanical, structural, and biologic effects.

One of the suspected deleterious effects of androgenic-anabolic steroids (AAS) is the increased risk for tendon rupture. However, investigations to date have produced inconsistent results and it is still unclear how AAS influence tendons. A systematic review of the literature was conducted to identify studies that have investigated the mechanical, structural, or biologic effects that AAS have on tendons. In total, 18 highly heterogeneous studies were identified. Small animal studies made up the vast majority of published research, and contradictory results were reported frequently. All of the included studies focused on the potential deleterious effects that AAS have on tendon, which is striking given the recent use of AAS in patients following tendon injury. Rather than providing strong evidence for or against the use of AAS, this review highlights the need for additional research. Future studies investigating the use of AAS as a possible treatment for tendon injury/pathology are supported by reports suggesting that AAS may counteract the irreparable structural/functional changes that occur in the musculotendinous unit following rotator cuff tears, as well as studies suggesting that the purported deleterious effects on tendon may be transient. Other possible areas for future research are discussed in the context of key findings that may have implications for the therapeutic application of AAS. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support.

Multiorgan dysfunction syndrome contributes to adverse outcomes in advanced heart failure (AdHF) patients after mechanical circulatory support (MCS) implantation and is associated with aberrant leukocyte activity. We tested the hypothesis that preoperative peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) can predict early postoperative improvement or non-improvement in patients undergoing MCS implantation. We believe this information may be useful in developing prognostic biomarkers.We conducted a study with 29 patients undergoing MCS-surgery in a tertiary academic medical center from 2012 to 2014. PBMC samples were collected one day before surgery (day -1). Clinical data was collected on day -1 and day 8 postoperatively. Patients were classified by Sequential Organ Failure Assessment score and Model of End-stage Liver Disease Except INR score (measured eight days after surgery): Group I = improving (both scores improved from day -1 to day 8, n = 17) and Group II = not improving (either one or both scores did not improve from day -1 to day 8, n = 12). RNA-sequencing was performed on purified mRNA and analyzed using Next Generation Sequencing Strand. Differentially expressed genes (DEGs) were identified by Mann-Whitney test with Benjamini-Hochberg correction. Preoperative DEGs were used to construct a support vector machine algorithm to predict Group I vs. Group II membership.Out of 28 MCS-surgery patients alive 8 days postoperatively, one-year survival was 88% in Group I and 27% in Group II. We identified 28 preoperative DEGs between Group I and II, with an average 93% prediction accuracy. Out of 105 DEGs identified preoperatively between year 1 survivors and non-survivors, 12 genes overlapped with the 28 predictive genes.In AdHF patients following MCS implantation, preoperative PBMC-GEP predicts early changes in organ function scores and correlates with long-term outcomes. Therefore, gene expression lends itself to outcome prediction and warrants further studies in larger longitudinal cohorts

Overlap of significant genes associated with organ function improvement and survival benefit.

<p>(A) Hierarchical clustering of significant genes day -1 (TP1). Left: The Volcano plot of 28 genes, which are differentially expressed between Group I and Group II. Right: Hierarchical clustering of the 28 candidate genes for the prediction test demonstrates the differential gene expression between Group I and Group II. (B) Hierarchical clustering of genes associated with survival benefit. Left: The Volcano plot of 105 genes, which are differentially expressed between Group I and Group II. Right: Hierarchical clustering of the 105 candidate genes for the prediction test demonstrates the differential gene expression between Group I = Survival, Group II = Non-survival. (C) Overlap genes from both improvement group and 1-year survival outcome. Left: Venn-Diagram shows the 28 DEGs identified in the comparison by improvement score (red) and the Right shows the 105 DEGs identified by comparing 1-Year Survival (blue). Twelve DEGs were shared across the two comparisons. Right: The 12 overlap genes (see text for details).</p