Investigating Coral Bleaching in a Changing Climate: Our State of Understanding and Opportunities to Push the Field Forward

[First Paragraph] Coral reefs throughout the world are facing the consequences of large-scale changes in Earth’s climate. In particular, ocean warming is leading to frequent coral bleaching, which is threatening the long-term stability of coral reefs. Coral bleaching is a stress response that results in the disassociation of the mutualistic symbioses (i.e., dysbiosis) between corals and their endosymbiotic algae (Symbiodinium spp.). In the past two decades, there have been four substantial bleaching events, which have affected large geographic areas across the globe, including the worst recorded bleaching event on the Great Barrier Reef in 2016 (Berkelmans et al. 2004; Eakin et al. 2010; Stella et al. 2016). These large-scale bleaching events, in combination with many local-scale stressors, have contributed substantially to global declines in coral populations. In addition, bleaching may lead to compromised coral immunity, possibly resulting in additional mortality by a range of post-bleaching diseases (Maynard et al. 2015, Randall et al. 2014). Given their link to patterns of global-climate change and projections of increased warming in the coming decades, mass coral bleaching events are a key concern. In addition, current climate projections estimate that global bleaching is expected to occur annually by late this century, with more than 90% of reefs facing long-term degradation (Frieler et al. 2012). Furthermore, in locations such as the Caribbean, frequent thermal anomalies and consecutive annual bleaching events are expected to be common in less than 25 years (van Hooidonk et al. 2015). In fact, large-scale bleaching two years in a row was documented for the first time in 2014-2015 in Hawaii and in the Florida Keys. However, not all corals (and other symbiotic cnidarians) are equally susceptible to thermal stress, and some corals have been shown to recover from bleaching more quickly than others. Likewise, not all reefs are equally susceptible, and depending on local conditions, susceptibility can vary from one event to the next. Such variability in resilience could be a cornerstone to reef persistence over the coming century. However, the research needed to test this hypothesis remains to be performed

The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects

High-resolution numerical modeling of wave-supported gravity-driven mudflows

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C05014, doi:10.1029/2008JC005006.Wave-supported gravity-driven mudflow has been identified as a major offshore fine sediment transport mechanism of terrestrial sediment into the coastal ocean. This transport process essentially occurs within the wave boundary layer. In this study, wave-supported gravity-driven mudflow is investigated via a wave-phase-resolving high-resolution numerical model for fluid mud transport. The model results are verified with field observation of sediment concentration and near-bed flow velocities at Po prodelta. The characteristics of wave-supported gravity-driven mudflows are diagnosed by varying the bed erodibility, floc properties (fractal dimension), and rheological stresses in the numerical simulations. Model results for moderate concentration suggest that using an appropriately specified fractal dimension, the dynamics of wave-supported gravity-driven mudflow can be predicted without explicitly incorporating rheological stress. However, incorporating rheological stress makes the results less sensitive to prescribed fractal dimension. For high-concentration conditions, it is necessary to incorporate rheological stress in order to match observed intensity of downslope gravity-driven current. Model results are further analyzed to evaluate and calibrate simple parameterizations. Analysis suggests that when neglecting rheological stress, the drag coefficient decreases with increasing wave intensity and seems to follow a power law. However, when rheological stress is incorporated, the resulting drag coefficient is more or less constant (around 0.0013) for different wave intensities. Model results further suggest the bulk Richardson number has a magnitude smaller than 0.25 and is essentially determined by the amount of available soft mud (i.e., the erodibility), suggesting a supply limited condition for unconsolidated mud.This study is supported by the Office of Naval Research grant N00014-09-1-0134 and grant N00014-06-1-0945 as part of the Community Sediment Transport Modeling System (CSTMS) through the National Oceanographic Partnership Program (NOPP). This study is also partially supported by National Science Foundation (OCE- 0644497)

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Pleasure and historical memory in Spanish Gothic film

This essay argues that scholars of Spanish culture are too ready to assume a reading of Gothic texts in terms of historical memory, or the rectification of injustices that occurred during the Franco era. It suggests that there has been a neglect of the question of the pleasures of reading or viewing the Gothic, even though these pleasures may well undermine the desire to do retrospective justice to the victims of Franco. Using as a case study the film Insensibles (Juan Carlos Medina 2012) this essay proposes some examples of pleasures that serve to disrupt the recuperation of historical memory, and calls for better awareness of the pleasures of genre in analysing relevant texts

Pre-operative pulmonary assessment for patients with hip fracture

Hip fracture is a common injury among the elderly. Although patients who receive hip fracture surgery carry the best functional recovery compared to other treatment modalities, the presence of postoperative pulmonary complications, such as atelectasis, pneumonia, and pulmonary thromboembolism, may contribute to increased length of hospital stay, perioperative morbidity, and mortality. This review aims to provide evidence-based recommendations for preoperative assessment and perioperative strategies to reduce the risk of pulmonary complications after hip fracture surgery. Clinical assessment and basic laboratory results are sufficient to stratify the risk of postoperative pulmonary complications. Well-documented risk factors for pulmonary complications include advanced age, poor general health status, current infections, pre-existing cardiopulmonary diseases, hypoalbuminemia, and impaired renal function. Apart from optimizing the patient's medical conditions, interventions such as lung expansion maneuvers and thromboprophylaxis have been proven to be effective in reducing the risk of pulmonary complications after hip fracture surgery

The Linkage Between Neighborhood and Voluntary Association Patterns: a Comparison of Black and White Urban Populations

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68314/2/10.1177_089976407400300201.pd

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Neoadjuvant Relatlimab and Nivolumab in Resectable Melanoma

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen

Body mass index and annual increase of body mass index in long-term childhood cancer survivors; relationship to treatment

Evaluation of body mass index (BMI) at final height (FH) and annual BMI increase in adult childhood cancer survivors (CCS) after treatment with anthracyclines, platinum, and/or radiotherapy. BMI (weight/heightA(2)) was calculated retrospectively from diagnosis until FH. The prevalence of underweight (BMI < 18.5 kg/m(2)) and overweight (BMI a parts per thousand yenaEuro parts per thousand 25 kg/m(2))/obesity (BMI a parts per thousand yenaEuro parts per thousand 30 kg/m(2)) at FH was compared with age-matched controls. The association between underweight/overweight at FH and treatment was assessed by multivariate logistic regression. Annual BMI increase after treatment was assessed by multilevel analysis. Analyses were adjusted for age and underweight/overweight at diagnosis, and age at FH. At FH the prevalence of overweight had not increased, while CCS experienced more underweight as compared to controls (14% vs. 4%, P < 0.001). Overweight at FH was associated with cranial/craniospinal radiotherapy (CRT; OR, 2.23; 95% CI, 1.17-4.26) and underweight at FH with anthracyclines > 300 mg/m(2) (OR, 2.84; 95% CI, 1.33-6.06). Annual BMI increase was +0.47 (0.34-0.60) kg/m(2)/year. In CCS, the annual BMI increase was greater in those with CRT a parts per thousand yenaEuro parts per thousand 30 Gy as compared with those with less or no CRT (+0.15 kg/m(2)/year [0.04-0.25 kg/m(2)/year], P = 0.008) and smaller in those with a higher cumulative anthracycline dose (-0.03 kg/m(2)/year [-0.05 to -0.0005 kg/m(2)/year] per 100 mg/m(2), P = 0.046). After treatment with anthracyclines, platinum, and/or radiotherapy, CRT-treated survivors have more overweight at FH, and a greater annual BMI increase, while anthracycline-treated survivors have more underweight at FH and a lower annual BMI increase