Testing the Utility of Geochemical Proxies to Reconstruct Holocene Coastal Environments and Relative Sea Level: A Case Study from Hungry Bay, Bermuda

On low-lying, tropical and sub-tropical coastlines freshwater marshes may be replaced by salt-tolerant mangroves in response to relative sea-level rise. Pollen analysis of radiocarbon-dated sediment cores showed that such a change occurred in Hungry Bay, Bermuda during the late Holocene. This well-established paleoenvironmental trajectory provides an opportunity to explore if geochemical proxies (bulk-sediment δ13C and Rock-Eval pyrolysis) can reconstruct known environmental changes and relative sea level. We characterized surface sediment from depositional environments in Bermuda (freshwater wetlands, saline mangroves, and wrack composed of Sargassum natans macroalgae) using geochemical measurements and demonstrate that a multi-proxy approach can objectively distinguish among these environments. However, application of these techniques to the transgressive sediment succession beneath Hungry Bay suggests that freshwater peat and mangrove peat cannot be reliably distinguished in the sedimentary record, possibly because of post-depositional convergence of geochemical characteristics on decadal to multi-century timescales and/or the relatively small number of modern samples analyzed. Sediment that includes substantial contributions from Sargassum is readily identified by geochemistry, but has a limited spatial extent. Radiocarbon dating indicates that beginning at –700 CE, episodic marine incursions into Hungry Bay (e.g., during storms) carried Sargassum that accumulated as wrack and thickened through repeated depositional events until ~300 CE. It took a further ~550 years for a peat-forming mangrove community to colonize Hungry Bay, which then accumulated sediment rapidly, but likely out of equilibrium with regional relative sea-level rise

The Loss of Species: Mangrove Extinction Risk and Geographic Areas of Global Concern

Mangrove species are uniquely adapted to tropical and subtropical coasts, and although relatively low in number of species, mangrove forests provide at least US $1.6 billion each year in ecosystem services and support coastal livelihoods worldwide. Globally, mangrove areas are declining rapidly as they are cleared for coastal development and aquaculture and logged for timber and fuel production. Little is known about the effects of mangrove area loss on individual mangrove species and local or regional populations. To address this gap, species-specific information on global distribution, population status, life history traits, and major threats were compiled for each of the 70 known species of mangroves. Each species' probability of extinction was assessed under the Categories and Criteria of the IUCN Red List of Threatened Species. Eleven of the 70 mangrove species (16%) are at elevated threat of extinction. Particular areas of geographical concern include the Atlantic and Pacific coasts of Central America, where as many as 40% of mangroves species present are threatened with extinction. Across the globe, mangrove species found primarily in the high intertidal and upstream estuarine zones, which often have specific freshwater requirements and patchy distributions, are the most threatened because they are often the first cleared for development of aquaculture and agriculture. The loss of mangrove species will have devastating economic and environmental consequences for coastal communities, especially in those areas with low mangrove diversity and high mangrove area or species loss. Several species at high risk of extinction may disappear well before the next decade if existing protective measures are not enforced

The loss of species: mangrove extinction risk and failure of critical exosystem services

Mangrove species are uniquely adapted to tropical and subtropical coasts, and although relatively low in number of species, mangrove forests provide at least US $1.6 billion each year in ecosystem services and support coastal livelihoods worldwide. Globally, mangrove areas are declining rapidly as they are cleared for coastal development and aquaculture and logged for timber and fuel production. Little is known about the effects of mangrove area loss on individual mangrove species and local or regional populations. To address this gap, species-specific information on global distribution, population status, life history traits, and major threats were compiled for each of the 70 known species of mangroves. Each species\u27 probability of extinction was assessed under the Categories and Criteria of the IUCN Red List of Threatened Species. Eleven of the 70 mangrove species (16%) are at elevated threat of extinction. Particular areas of geographical concern include the Atlantic and Pacific coasts of Central America, where as many as 40% of mangroves species present are threatened with extinction. Across the globe, mangrove species found primarily in the high intertidal and upstream estuarine zones, which often have specific freshwater requirements and patchy distributions, are the most threatened because they are often the first cleared for development of aquaculture and agriculture. The loss of mangrove species will have devastating economic and environmental consequences for coastal communities, especially in those areas with low mangrove diversity and high mangrove area or species loss. Several species at high risk of extinction may disappear well before the next decade if existing protective measures are not enforced

Interrogating resilience: toward a typology to improve its operationalization

In the context of accelerated global change, the concept of resilience, with its roots in ecological theory and complex adaptive systems, has emerged as the favored framework for understanding and responding to the dynamics of change. Its transfer from ecological to social contexts, however, has led to the concept being interpreted in multiple ways across numerous disciplines causing significant challenges for its practical application. The aim of this paper is to improve conceptual clarity within resilience thinking so that resilience can be interpreted and articulated in ways that enhance its utility and explanatory power, not only theoretically but also operationally. We argue that the current confusion and ambiguity within resilience thinking is problematic for operationalizing the concept within policy making. To achieve our aim, we interrogate resilience interpretations used within a number of academic and practice domains in the forefront of contending with the disruptive and sometimes catastrophic effects of global change (primarily due to climate change) on ecological and human-nature systems. We demonstrate evolution and convergence among disciplines in the interpretations and theoretical underpinnings of resilience and in engagement with cross-scale considerations. From our analysis, we identify core conceptual elements to be considered in policy responses if resilience is to fulfill its potential in improving decision making for change. We offer an original classification of resilience definitions in current use and a typology of resilience interpretations. We conclude that resilience thinking must be open to alternative traditions and interpretations if it is to become a theoretically and operationally powerful paradigm

Studying Early Lethality of 45,XO (Turner's Syndrome) Embryos Using Human Embryonic Stem Cells

Turner's syndrome (caused by monosomy of chromosome X) is one of the most common chromosomal abnormalities in females. Although 3% of all pregnancies start with XO embryos, 99% of these pregnancies terminate spontaneously during the first trimester. The common genetic explanation for the early lethality of monosomy X embryos, as well as the phenotype of surviving individuals is haploinsufficiency of pseudoautosomal genes on the X chromosome. Another possible mechanism is null expression of imprinted genes on the X chromosome due to the loss of the expressed allele. In contrast to humans, XO mice are viable, and fertile. Thus, neither cells from patients nor mouse models can be used in order to study the cause of early lethality in XO embryos. Human embryonic stem cells (HESCs) can differentiate in culture into cells from the three embryonic germ layers as well as into extraembryonic cells. These cells have been shown to have great value in modeling human developmental genetic disorders. In order to study the reasons for the early lethality of 45,XO embryos we have isolated HESCs that have spontaneously lost one of their sex chromosomes. To examine the possibility that imprinted genes on the X chromosome play a role in the phenotype of XO embryos, we have identified genes that were no longer expressed in the mutant cells. None of these genes showed a monoallelic expression in XX cells, implying that imprinting is not playing a major role in the phenotype of XO embryos. To suggest an explanation for the embryonic lethality caused by monosomy X, we have differentiated the XO HESCs in vitro an in vivo. DNA microarray analysis of the differentiated cells enabled us to compare the expression of tissue specific genes in XO and XX cells. The tissue that showed the most significant differences between the clones was the placenta. Many placental genes are expressed at much higher levels in XX cells in compare to XO cells. Thus, we suggest that abnormal placental differentiation as a result of haploinsufficiency of X-linked pseudoautosomal genes causes the early lethality in XO human embryos

Advertising Bans and the Substitutability of Online and Offline Advertising

The authors examine whether the growth of the Internet has reduced the effectiveness of government regulation of advertising. They combine nonexperimental variation in local regulation of offline alcohol advertising with data from field tests that randomized exposure to online advertising for 275 different online advertising campaigns to 61,580 people. The results show that people are 8% less likely to say that they will purchase an alcoholic beverage in states that have alcohol advertising bans compared with states that do not. For consumers exposed to online advertising, this gap narrows to 3%. There are similar effects for four changes in local offline alcohol advertising restrictions when advertising effectiveness is observed both before and after the change. The effect of online advertising is disproportionately high for new products and for products with low awareness in places that have bans. This suggests that online advertising could reduce the effectiveness of attempts to regulate offline advertising channels because online advertising substitutes for (rather than complements) offline advertising.Google (Firm)WPP (Firm

Application of Ligninolytic Enzymes in the Production of Biofuels from Cotton Wastes

The application of ligninolytic fungi and enzymes is an option to overcome the issues related with the production of biofuels using cotton wastes. In this dissertation, the ligninolytic fungus and enzymes were evaluated as pretreatment for the biochemical conversion of Cotton Gin Trash (CGT) in ethanol and as a treatment for the transformation of cotton wastes biochar in other substances. In biochemical conversion, seven combinations of three pretreatments (ultrasonication, liquid hot water and ligninolytic enzymes) were evaluated on CGT. The best results were achieved by the sequential combination of ultrasonication, hot water, and ligninolytic enzymes with an improvement of 10% in ethanol yield. To improve these results, alkaline-ultrasonication was evaluated. Additionally, Fourier Transform Infrared (FT-IR) and principal component analysis (PCA) were employed as fast methodology to identify structural differences in the biomass. The combination of ultrasonication-alkali hydrolysis, hot liquid water, and ligninolytic enzymes using 15% of NaOH improved 35% ethanol yield compared with the original treatment. Additionally, FT-IR and PCA identified modifications in the biomass structure after different types of pretreatments and conditions. In thermal conversion, this study evaluated the biodepolymerization of cotton wastes biochar using chemical and biological treatments. The chemical depolymerization evaluated three chemical agents (KMnO4, H2SO4, and NaOH), with three concentrations and two environmental conditions. The sulfuric acid treatments performed the largest transformations of the biochar solid phase; whereas, the KMnO4 treatments achieved the largest depolymerizations. The compounds released into the liquid phase were correlated with fulvic and humic acids and silicon compounds. The biological depolymerization utilized four ligninolytic fungi Phanerochaete chrysosporium, Ceriporiopsis subvermispora, Postia placenta, and Bjerkandera adusta. The greatest depolymerization was obtained by C. subvermispora. The depolymerization kinetics of C. subvermispora evidenced the production of laccase and manganese peroxidase and a correlation between depolymerization and production of ligninolytic enzymes. The modifications obtained in the liquid and solid phases showed the production of humic and fulvic acids from the cultures with C. subvermispora. The results of this research are the initial steps for the development of new processes using the ligninolytic fungus and their enzymes for the production of biofuels from cotton wastes

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Failure of human rhombic lip differentiation underlies medulloblastoma formation

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain 1–4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage 5–8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES +KI67 + unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB