Reconstructions of eolian dust accumulation in northwest African margin sediments

Reconstructions of eolian dust accumulation in northwest African margin sediments provide important continuous records of past changes in atmospheric circulation and aridity in the region. Existing records indicate dramatic changes in North African dust emissions over the last 20 ka, but the limited spatial extent of these records and the lack of high-resolution flux data do not allow us to determine whether changes in dust deposition occurred with similar timing, magnitude and abruptness throughout northwest Africa. Here we present new records from a meridional transect of cores stretching from 31°N to 19°N along the northwest African margin. By combining grain size endmember modeling with 230Th-normalized fluxes for the first time, we are able to document spatial and temporal changes in dust deposition under the North African dust plume throughout the last 20 ka. Our results provide quantitative estimates of the magnitude of dust flux changes associated with Heinrich Stadial 1, the Younger Dryas, and the African Humid Period (AHP; ~11.7-5 ka), offering robust targets for model-based estimates of the climatic and biogeochemical impacts of past changes in North African dust emissions. Our data suggest that dust fluxes between 8 and 6 ka were a factor of ~5 lower than average fluxes during the last 2 ka. Using a simple model to estimate the effects of bioturbation on dust input signals, we find that our data are consistent with abrupt, synchronous changes in dust fluxes in all cores at the beginning and end of the AHP. The mean ages of these transitions are 11.8±0.2 ka (1Sigma) and 4.9±0.2 ka, respectively.

Seawater carbonate chemistry and egg production, hatching and metabolic rates of a Mediterranean copepod species (Acartia clausi) in a laboratory experiment

This study includes the first information on the combined effect of low pH and raised temperature on egg production rate (EP), hatching success (HS), excretion and respiration of the Mediterranean copepod Acartia clausi. Adult individuals of A. clausi and fresh surface seawater were collected at a coastal station in Saronikos Gulf during April 2012. Four different conditions were applied: two different pH levels (present: 8.09 and future: 7.83) at two temperature values (present: 16°C and present+4 °C= 20°C). EP and HS success decreased significantly over the duration of exposure at future pH at both temperature conditions. However, the analysis of the combined effect of pH, T, chlorophyll a and the duration of the experiments on EP and HS revealed that ocean acidification had no discernible effect, whereas warming; food and the duration of exposure were more significant for the reproductive output of A. clausi. Temperature appeared to have a positive effect on respiration and excretion. Acidification had no clear effect on respiration, but a negative effect on the A. clausi excretion was observed. Acidification and warming resulted in the increase of the excretion rate and the increase was higher than that observed by warming only. Our findings showed that a direct effect of ocean acidification on copepod's vital rates was not obvious, except maybe in the case of excretion. Therefore, the combination of acidification with the ambient oligotrophic conditions and the warming could result in species being less able to allocate resources for coping with multiple stressors.

Life expectancy for community-based patients with heart failure from time of diagnosis

AIMS: Heart failure has been demonstrated in previous studies to have a dismal prognosis. However, the modern-day prognosis of patients with new onset heart failure diagnosed in the community managed within a disease management programme is not known. The purpose of this study is to report on prognosis of patients presenting with new onset heart failure in the community who are subsequently followed in a disease management program.

METHODS AND RESULTS: A review of patients referred to a rapid access heart failure diagnostic clinic between 2002 and 2012 was undertaken. Details of diagnosis, demographics, medical history, medications, investigations and mortality data were analysed. A total of 733 patients were seen in Rapid Access Clinic for potential new diagnosis of incident of heart failure. 38.9% (n=285) were diagnosed with heart failure, 40.7% (n=116) with HF-REF and 59.3% (n=169) with HF-PEF. There were 84 (29.5%) deaths in the group of patients diagnosed with heart failure; 41 deaths (35.3%) occurred in patients with HF-REF and 43 deaths (25.4%) occurred in patients with HF-PEF. In patients with heart failure, 52.4% (n=44) died from cardiovascular causes. 63.8% of HF patients were alive after 5 years resulting on average in a month per year loss of life expectancy over that period compared with aged matched simulated population.

CONCLUSIONS: In this community-based cohort, the prognosis of heart failure was better than reported in previous studies. This is likely due to the impact of prompt diagnosis, the improvement in therapies and care within a disease management structure.

Printmare Against Nature

Nicky Coutts showed a work in the show "Printmare: Against Nature 1", reproducing a miniature storm scene from a Scottish five pound note and an essay titled "Animal Print Suicide" for the accompanying publication "Printmare Against Nature 2". Curated by Finlay Taylor, ‘Against Nature’ was an exhibition exploring conditions of current understandings of geography (or the geo-graphical), natural histories and landscapes. This exhibition concentrated on work that uses print, and the ways in which subtle innovations in this medium are used to investigate some of the complexities that arise when looking at nature in art. An associated publication has been published by Camberwell Press with essays by David Cross and Nicky Coutts, as well as page images by Bob Matthews, Denis Masi, Finlay Taylor, Kate Scrivener and Dick Jewell. Exhibiting artists included Franz Ackermann, Jasone Miranda Bilbao, Sarah Bodman, Ian Brown, Helen Chadwick, Paul Coldwell, Cornford and Cross, Nicky Coutts, Dunhill & O’Brien, Adam Gillam, Oona Grimes, Judith Goddard, Mark Harris, Katsushika Hokusai, Dan Howard-Birt, Susan Johanknecht, James Keith, Serena Korda, Michael Landy, Jo Love, Mike Marshall, Bob Matthews, Julian Opie, Tim O’Riley, Simon Patterson, David Rayson, Rebecca Salter, Kate Scrivener, Jo Stockham, and Herman de Vries.

Sex steroid feedback regulation of pituitary gonadotropins during early secondary oocyte growth in coho salmon (Oncorhynchus kisutch) – a potential target of endocrine disruption.

Thesis (Ph.D.)--University of Washington, 2016-06

Genome Wide Association Studies of Phagocytosis and the Cellular Immune Response in Drosophila melanogaster.

Phagocytosis of bacteria by specialized blood cells, known as hemocytes, is a vital component of Drosophila cellular immunity. To identify novel genes that mediate the cellular response to bacteria, we conducted three separate genetic screens using the Drosophila Genetic Reference Panel (DGRP). Adult DGRP lines were tested for the ability of their hemocytes to phagocytose the Gram-positive bacteria Staphylococcus aureus or the Gram-negative bacteria Escherichia coli. The DGRP lines were also screened for the ability of their hemocytes to clear S. aureus infection through the process of phagosome maturation. Genome-wide association analyses were performed to identify potentially relevant single nucleotide polymorphisms (SNPs) associated with the cellular immune phenotypes. The S. aureus phagosome maturation screen identified SNPs near or in 528 candidate genes, many of which have no known role in immunity. Three genes, dpr10, fred, and CG42673, were identified whose loss-of-function in blood cells significantly impaired the innate immune response to S. aureus. The DGRP S. aureus screens identified variants in the gene, Ataxin 2 Binding Protein-1 (A2bp1) as important for the cellular immune response to S. aureus. A2bp1 belongs to the highly conserved Fox-1 family of RNA-binding proteins. Genetic studies revealed that A2bp1 transcript levels must be tightly controlled for hemocytes to successfully phagocytose S. aureus. The transcriptome of infected and uninfected hemocytes from wild type and A2bp1 mutant flies was analyzed and it was found that A2bp1 negatively regulates the expression of the Immunoglobulin-superfamily member Down syndrome adhesion molecule 4 (Dscam4). Silencing of A2bp1 and Dscam4 in hemocytes rescues the fly’s immune response to S. aureus indicating that Dscam4 negatively regulates S. aureus phagocytosis. Overall, we present an examination of the cellular immune response to bacteria with the aim of identifying and characterizing roles for novel mediators of innate immunity in Drosophila. By screening panel of lines in which all genetic variants are known, we successfully identified a large set of candidate genes that could provide a basis for future studies of Drosophila cellular immunity. Finally, we describe a novel, immune-specific role for the highly conserved Fox-1 family member, A2bp1.

Essays on the Effects of Social Insurance for Disability

This dissertation examines how social insurance, family support and work capacity enhance individuals' economic well-being following significant health and income shocks. I first examine the extent to which the liquidity-enhancing effects of Worker's Compensation (WC) benefits outweigh the moral hazard costs. Analyzing administrative data from Oregon, I estimate a hazard model exploiting variation in the timing and size of a retroactive lump-sum WC payment to decompose the elasticity of claim duration with respect to benefits into the elasticity with respect to an increase in cash on hand, and a decrease in the opportunity cost of missing work. I find that the liquidity effect accounts for 60 to 65 percent of the increase in claim duration among lower-wage workers, but less than half of the increase for higher earners. Using the framework from Chetty (2008), I conclude that the insurance value of WC exceeds the distortionary cost, and increasing the benefit level could increase social welfare. Next, I investigate how government-provided disability insurance (DI) interacts with private transfers to disabled individuals from their grown children. Using the Health and Retirement Study, I estimate a fixed effects, difference in differences regression to compare transfers between DI recipients and two control groups: rejected applicants and a reweighted sample of disabled non-applicants. I find that DI reduces the probability of receiving a transfer by no more than 3 percentage points, or 10 percent. Additional analysis reveals that DI could increase the probability of receiving a transfer in cases where children had limited prior information about the disability, suggesting that DI could send a welfare-improving information signal. Finally, Zachary Morris and I examine how a functional assessment could complement medical evaluations in determining eligibility for disability benefits and in targeting return to work interventions. We analyze claimants' self-reported functional capacity in a survey of current DI beneficiaries to estimate the share of disability claimants able to do work-related activity. We estimate that 13 percent of current DI beneficiaries are capable of work-related activity. Furthermore, other characteristics of these higher-functioning beneficiaries are positively correlated with employment, making them an appropriate target for return to work interventions.

An investigation into the folding and assembly of engineered antibodies and novel antibody formats

Monoclonal antibodies and novel antibody formats are currently one of the principal therapeutic in the biopharmaceutical industry worldwide and are widely used in the treatment of autoimmune diseases and cancer. It is for this reason that the productivity and quality of antibody production requires improvement; specifically investigations into the engineering of antibodies and any issues that may arise from the production of these therapeutics. The work presented in this thesis describes an investigation into the folding and assembly of seven antibodies plus the novel antibody format FabFv. IgG is comprised of two identical HCs and two identical LCs. The folding process of immunoglobulin is controlled by the CH1 domain within the HC. The CH1 domain remains in a disordered state and is sequestered by BiP in the endoplasmic reticulum. Upon the addition of a folded CL domain, BiP is displaced, the CH1 domain is able to fold and the complete IgG protein can then be secreted from the cell. The results presented in this thesis however, have outlined an additional mechanism for the folding of the CH1 domain. We have shown that the CH1 domain is able to fold in the absence of LC resulting in the secretion of HC dimers in a VH dependent manner. The proposed mechanism for the secretion of HC dimers suggests that some VH domains can interact with each other in order to bring the CH1 domains in close proximity to enable folding to occur. As HC dimer secretion is a hindrance in antibody production, this result has highlighted an engineering target to improve antibody yield. Examination of the folding of IgG4 with the variable region A33 has revealed the inability to secrete LC dimers, cleavage of the HC during expression and secretion of HC dimers in the Fab, FabFv and full length forms. The attributes described have also been shown to be variable region dependent. This has introduced a new concept that the variable domain is important in determining the expression and secretion of antibodies and their individual chains. Pulse chase and 2D gel electrophoresis analysis of the novel antibody format FabFv has revealed that the folding and expression of the LC and HC causes multimeric species of FabFv to be secreted, as opposed to the monomeric form which is the desired therapeutic. Our hypothesis is that this process occurs via a LC dependent mechanism. The proposed hypothesis suggests that further engineering to the LC could diminish the formation and secretion of FabFv multimers. The results from these investigations can be applied to increase the productivity of therapeutics and increase the biological understanding of the domain interactions of IgG during folding, assembly and secretion.