Mitigating anthropogenic climate change with aqueous green energy.

Reaching net zero emissions and limiting global warming to 2 °C requires the widespread introduction of technology-based solutions to draw down existing atmospheric levels and future emissions of CO. One such approach is direct air CO capture and storage (DACCS), a readily available, yet energy-intensive process. The combination of DACCS and ocean thermal energy conversion (OTEC) allows for independently powered carbon capture plants to inject concentrated carbon into deep marine sediments where storage is generally safe and permanent.

Do Prophylactic Inferior Vena Cava Filters Affect the Rates of Venous Thromboembolism and Pulmonary Embolism in Patients Undergoing Major Spine Surgery?

Study Design: Retrospective Analysis.

Background: Venous thromboembolism (VTE) represents a significant cause of morbidity and mortality in major spine surgery. Placement of prophylactic inferior vena cava filters (IVCF) in patients undergoing major spine surgery was previously adopted at our institution.

Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with a complex underlying genetic etiology. Herein, we conduct whole-exome sequencing of a multigeneration EoE pedigree (discovery set) and 61 additional multiplex families with EoE (replication set). A series of rare, heterozygous, missense variants are identified in the genes encoding the desmosome-associated proteins DSP and PPL in 21% of the multiplex families.

Immersion in Raloxifene does not significantly improve bone toughness or screw pull-out strength in multiple in vitro models.

Background: Failure of surgical fixation in orthopaedic fractures occurs at a significantly higher rate in osteoporotic patients due to weakened osteoporotic bone. A therapy to acutely improve the mechanical properties of bone during fracture repair would have profound clinical impact. A previous study has demonstrated an increase in mechanical properties of acellular cortical canine bone after immersion in raloxifene.

Nanofibrous hyaluronic acid scaffolds delivering TGF-β3 and SDF-1α for articular cartilage repair in a large animal model.

Focal cartilage injuries have poor intrinsic healing potential and often progress to osteoarthritis, a costly disease affecting almost a third of adults in the United States. To treat these patients, cartilage repair therapies often use cell-seeded scaffolds, which are limited by donor site morbidity, high costs, and poor efficacy. To address these limitations, we developed an electrospun cell-free fibrous hyaluronic acid (HA) scaffold that delivers factors specifically designed to enhance cartilage repair: Stromal Cell-Derived Factor-1α (SDF-1α; SDF) to increase the recruitment and infiltration of mesenchymal stem cells (MSCs) and Transforming Growth Factor-β3 (TGF-β3; TGF) to enhance cartilage tissue formation.

Resorbable Pins to Enhance Scaffold Retention in a Porcine Chondral Defect Model.

Objective: Cartilage repair strategies have seen improvement in recent years, especially with the use of scaffolds that serve as a template for cartilage formation. However, current fixation strategies are inconsistent with regards to retention, may be technically challenging, or may damage adjacent tissues or the implant itself. Therefore, the goal of this study was to evaluate the retention and repair potential of cartilage scaffolds fixed with an easy-to-implement bioresorbable pin.

Transection of the medial meniscus anterior horn results in cartilage degeneration and meniscus remodeling in a large animal model.

The meniscus plays a central load-bearing role in the knee joint. Unfortunately, meniscus injury is common and can lead to joint degeneration and osteoarthritis (OA). In small animal models, progressive degenerative changes occur with the unloading of the meniscus via destabilization of the medial meniscus (DMM).

Pediatric Hypereosinophilia: Characteristics, Clinical Manifestations, and Diagnoses.

Background: Eosinophilia is associated with various conditions, including allergic, infectious, and neoplastic disorders. The diagnostic differential is broad, and data on hypereosinophilia in pediatric patients are limited.

Objective: The objectives of this study were to identify cases of hypereosinophilia in a tertiary pediatric medical center, determine clinical characteristics and disease associations, and estimate the incidence of hypereosinophilia in the hospital and geographic populations.

Prevalence of eosinophilic colitis and the diagnoses associated with colonic eosinophilia.

Pediatric eosinophilic colitis (EC) is a rare disease with a prevalence of ~1/63,000 individuals, and at our tertiary care pediatric medical center, only 2% of patients with the ICD-9/10 code for EC likely have the disease.

Alignment of parent- and child-reported outcomes and histology in eosinophilic esophagitis across multiple CEGIR sites.

Background: Patient-reported outcome metrics for eosinophilic esophagitis (EoE) have been developed and validated but not used in a multicenter pediatric population or systematically aligned with histology.

Objective: We sought to understand (1) the potential of caregiver report to predict patient self-reported symptoms and (2) the correlation of patient-reported outcome domains with histology.

Methods: Patients with EoE (n = 310) and their parents participating in the Consortium of Gastrointestinal Eosinophilic Disease Researchers (CEGIR) observational clinical trial were queried for baseline patient symptoms and quality of life (QOL) by using the Pediatric Eosinophilic Esophagitis Symptom Score, version 2 (PEESSv2.

Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study.

Background: Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical-pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states.

Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci.

Background: Eosinophilic esophagitis (EoE) is an esophageal inflammatory disease associated with atopic diseases. Thymic stromal lymphopoietin (TSLP) and calpain 14 (CAPN14) genetic variations contribute to EoE, but how this relates to atopy is unclear.

Objective: The purpose of this study was to explore the relationship between EoE, atopy, and genetic risk.

Deforestation Induced Climate Change: Effects of Spatial Scale.

Deforestation is associated with increased atmospheric CO2 and alterations to the surface energy and mass balances that can lead to local and global climate changes. Previous modelling studies show that the global surface air temperature (SAT) response to deforestation depends on latitude, with most simulations showing that high latitude deforestation results in cooling, low latitude deforestation causes warming and that the mid latitude response is mixed. These earlier conclusions are based on simulated large scal land cover change, with complete removal of trees from whole latitude bands.

Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease.

Background: The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastroesophageal reflux disease [GERD], nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear.

Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown.

Objective: To quantify the risk associated with genes and environment on familial clustering of EoE.

Methods: Family history was obtained from a hospital-based cohort of 914 EoE probands (n = 2192 first-degree "Nuclear-Family" relatives) and an international registry of monozygotic and dizygotic twins/triplets (n = 63 EoE "Twins" probands).

PedsQL eosinophilic esophagitis module: feasibility, reliability, and validity.

Objective: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory condition with a paucity of information on health-related quality of life (HRQOL). The objective of the study was to report on the measurement properties of the PedsQL EoE Module.

Methods: The PedsQL EoE Module was completed in a multisite study by 196 pediatric patients with EoE and 262 parents of patients with EoE.

Auto-transfusion tourniquets: the next evolution of tourniquets.

In this article, we discuss the relationship between hemorrhagic shock and the pathophysiology of shock using conventional tourniquets. We will focus on corollary benefits with the use of HemaClear(®), a self-contained, sterile, exsanguinating auto-transfusion tourniquet. This discussion will demonstrate that the use of auto-transfusion tourniquets is a practical evidence-based approach in fluid resuscitation: it shortens the duration of shock after hemorrhage and trauma compared with conventional tourniquets.

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers.

Background: The role of microRNAs (miRNAs), a key class of regulators of mRNA expression and translation, in patients with eosinophilic esophagitis (EoE) has not been explored.

Objective: We aimed to identify miRNAs dysregulated in patients with EoE and assess the potential of these miRNAs as disease biomarkers.

Methods: Esophageal miRNA expression was profiled in patients with active EoE and those with glucocorticoid-induced disease remission.

Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation.

Members of the mammalian phosphoinositide-3-OH kinase (PI3K) family of proteins are critical regulators of various cellular process including cell survival, growth, proliferation, and motility. Oncogenic activating mutations in the p110alpha catalytic subunit of the heterodimeric p110/p85 PI3K enzyme are frequent in human cancers. Here we show the presence of frequent mutations in p85alpha in colon cancer, a majority of which occurs in the inter-Src homology-2 (iSH2) domain.

Setting cumulative emissions targets to reduce the risk of dangerous climate change.

Avoiding "dangerous anthropogenic interference with the climate system" requires stabilization of atmospheric greenhouse gas concentrations and substantial reductions in anthropogenic emissions. Here, we present an inverse approach to coupled climate-carbon cycle modeling, which allows us to estimate the probability that any given level of carbon dioxide (CO2) emissions will exceed specified long-term global mean temperature targets for "dangerous anthropogenic interference," taking into consideration uncertainties in climate sensitivity and the carbon cycle response to climate change. We show that to stabilize global mean temperature increase at 2 degrees C above preindustrial levels with a probability of at least 0.

Comment on "Saturation of the southern ocean CO2 sink due to recent climate change".

We disagree with the conclusion of Le Quéré et al. (Reports, 22 June 2007, p. 1735) that poleward intensifying winds could continue to weaken the Southern Ocean sink in the future.

DUBA: a deubiquitinase that regulates type I interferon production.

Production of type I interferon (IFN-I) is a critical host defense triggered by pattern-recognition receptors (PRRs) of the innate immune system. Deubiquitinating enzyme A (DUBA), an ovarian tumor domain-containing deubiquitinating enzyme, was discovered in a small interfering RNA-based screen as a regulator of IFN-I production. Reduction of DUBA augmented the PRR-induced IFN-I response, whereas ectopic expression of DUBA had the converse effect.

Regulation of ERK3/MAPK6 expression by BRAF.

Several forms of cancer are characterized by frequent activating mutations in the serine/threonine kinase, BRAF. Substitution of glutamic acid for valine at codon 600 (V600E) accounts for approximately 90% of all BRAF activating mutations and leads to stimulation of kinase activity, downstream signaling, and cell transformation. To better understand the molecular pathogenesis induced by oncogenic BRAF signaling, we used microarray gene expression profiling to comprehensively analyze the BRAF-directed transcriptional program of cells expressing a conditionally active form of BRAFV600E.

ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage.

The ataxia telangiectasia mutated (ATM) protein kinase is a critical component of a DNA-damage response network configured to maintain genomic integrity. The abundance of an essential downstream effecter of this pathway, the tumor suppressor protein p53, is tightly regulated by controlled degradation through COP1 and other E3 ubiquitin ligases, such as MDM2 and Pirh2; however, the signal transduction pathway that regulates the COP1-p53 axis following DNA damage remains enigmatic. We observed that in response to DNA damage, ATM phosphorylated COP1 on Ser(387) and stimulated a rapid autodegradation mechanism.