An integrated alcohol abuse and medical treatment model for patients with hepatitis C.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection have high rates of alcohol consumption, which is associated with progression of fibrosis and lower response rates to HCV treatment. AIMS: This prospective cohort study examined the feasibility of a 24-week integrated alcohol and medical treatment to HCV-infected patients. METHODS: Patients were recruited from a hepatology clinic if they had an Alcohol Use Disorders Identification Test score >4 for women and >8 for men, suggesting hazardous alcohol consumption. The integrated model included patients receiving medical care and alcohol treatment within the same clinic. Alcohol treatment consisted of 6 months of group and individual therapy from an addictions specialist and consultation from a study team psychiatrist as needed. RESULTS: Sixty patients were initially enrolled, and 53 patients participated in treatment. The primary endpoint was the Addiction Severity Index (ASI) alcohol composite scores, which significantly decreased by 0.105 (41.7% reduction) between 0 and 3 months (P < 0.01) and by 0.128 (50.6% reduction) between 0 and 6 months (P < 0.01) after adjusting for covariates. Alcohol abstinence was reported by 40% of patients at 3 months and 44% at 6 months. Patients who did not become alcohol abstinent had reductions in their ASI alcohol composite scores from 0.298 at baseline to 0.219 (26.8% reduction) at 6 months (P = 0.08). CONCLUSION: This study demonstrated that an integrated model of alcohol treatment and medical care could be successfully implemented in a hepatology clinic with significant favorable impact on alcohol use and abstinence among patients with chronic HCV.

Biological and ecological mechanisms supporting marine self-governance: The Seri Callo de Hacha Fishery in Mexico

My goal was to describe how biological and ecological factors give shape to fishing practices that can contribute to the successful self-governance of a small-scale fishing system in the Gulf of California, Mexico. The analysis was based on a comparison of the main ecological and biological indicators that fishers claim to use to govern their day-to-day decision making about fishing and data collected in situ. I found that certain indicators allow fishers to learn about differences and characteristics of the resource system and its units. Fishers use such information to guide their day-to-day fishing decisions. More importantly, these decisions appear unable to shape the reproductive viability of the fishery because no indicators were correlated to the reproductive cycle of the target species. As a result, the fishing practices constitute a number of mechanisms that might provide short-term buffering capacity against perturbations or stress factors that otherwise would threaten the overall sustainability and self-governance of the system. The particular biological circumstances that shape the harvesting practices might also act as a precursor of self-governance because they provide fishers with enough incentives to meet the costs of organizing the necessary rule structure that underlies a successful self-governance system.

Biological and physical interactions on a tropical island coral reef: Transport and retention processes on moorea, French Polynesia

The Moorea Coral Reef Long Term Ecological Research project funded by the US National Science Foundation includes multidisciplinary studies of physical processes driving ecological dynamics across the fringing reef, back reef, and fore reef habitats of Moorea, French Polynesia. A network of oceanographic moorings and a variety of other approaches have been used to investigate the biological and biogeochemical aspects of water transport and retention processes in this system. There is evidence to support the hypothesis that a low-frequency counterclockwise flow around the island is superimposed on the relatively strong alongshore currents on each side of the island. Despite the rapid flow and flushing of the back reef, waters over the reef display chemical and biological characteristics distinct from those offshore. The patterns include higher nutrient and lower dissolved organic carbon concentrations, distinct microbial community compositions among habitats, and reef assemblages of zooplankton that exhibit migration behavior, suggesting multigenerational residence on the reef. Zooplankton consumption by planktivorous fish on the reef reflects both retention of reef-associated taxa and capture by the reef community of resources originating offshore. Coral recruitment and population genetics of reef fishes point to retention of larvae within the system and high recruitment levels from local adult populations. The combined results suggest that a broad suite of physical and biological processes contribute to high retention of externally derived and locally produced organic materials within this island coral reef system. © 2013 by The Oceanography Society. All rights reserved.

High-Resolution In Situ Oxygen-Argon Studies of Surface Biological and Physical Processes in the Polar Oceans

The Arctic Ocean and Western Antarctic Peninsula (WAP) are the fastest warming regions on the planet and are undergoing rapid climate and ecosystem changes. Until we can fully resolve the coupling between biological and physical processes we cannot predict how warming will influence carbon cycling and ecosystem function and structure in these sensitive and climactically important regions. My dissertation centers on the use of high-resolution measurements of surface dissolved gases, primarily O2 and Ar, as tracers or physical and biological functioning that we measure underway using an optode and Equilibrator Inlet Mass Spectrometry (EIMS). Total O2 measurements are common throughout the historical and autonomous record but are influenced by biological (net metabolic balance) and physical (temperature, salinity, pressure changes, ice melt/freeze, mixing, bubbles and diffusive gas exchange) processes. We use Ar, an inert gas with similar solubility properties to O2, to devolve distinct records of biological (O2/Ar) and physical (Ar) oxygen. These high-resolution measurements that expose intersystem coupling and submesoscale variability were central to studies in the Arctic Ocean, WAP and open Southern Ocean that make up this dissertation.

Key findings of this work include the documentation of under ice and ice-edge blooms and basin scale net sea ice freeze/melt processes in the Arctic Ocean. In the WAP O2 and pCO2 are both biologically driven and net community production (NCP) variability is controlled by Fe and light availability tied to glacial and sea ice meltwater input. Further, we present a feasibility study that shows the ability to use modeled Ar to derive NCP from total O2 records. This approach has the potential to unlock critical carbon flux estimates from historical and autonomous O2 measurements in the global oceans.

Biological and Physical Factors Affecting the Natural History and Evolution of Encapsulated Development

The evolution of reproductive strategies involves a complex calculus of costs and benefits to both parents and offspring. Many marine animals produce embryos packaged in tough egg capsules or gelatinous egg masses attached to benthic surfaces. While these egg structures can protect against environmental stresses, the packaging is energetically costly for parents to produce. In this series of studies, I examined a variety of ecological factors affecting the evolution of benthic development as a life history strategy. I used marine gastropods as my model system because they are incredibly diverse and abundant worldwide, and they exhibit a variety of reproductive and developmental strategies.

The first study examines predation on benthic egg masses. I investigated: 1) behavioral mechanisms of predation when embryos are targeted (rather than the whole egg mass); 2) the specific role of gelatinous matrix in predation. I hypothesized that gelatinous matrix does not facilitate predation. One study system was the sea slug Olea hansineensis, an obligate egg mass predator, feeding on the sea slug Haminoea vesicula. Olea fed intensely and efficiently on individual Haminoea embryos inside egg masses but showed no response to live embryos removed from gel, suggesting that gelatinous matrix enables predation. This may be due to mechanical support of the feeding predator by the matrix. However, Haminoea egg masses outnumber Olea by two orders of magnitude in the field, and each egg mass can contain many tens of thousands of embryos, so predation pressure on individuals is likely not strong. The second system involved the snail Nassarius vibex, a non-obligate egg mass predator, feeding on the polychaete worm Clymenella mucosa. Gel neither inhibits nor promotes embryo predation for Nassarius, but because it cannot target individual embryos inside an egg mass, its feeding is slow and inefficient, and feeding rates in the field are quite low. However, snails that compete with Nassarius for scavenged food have not been seen to eat egg masses in the field, leaving Nassarius free to exploit the resource. Overall, egg mass predation in these two systems likely benefits the predators much more than it negatively affects the prey. Thus, selection for environmentally protective aspects of egg mass production may be much stronger than selection for defense against predation.

In the second study, I examined desiccation resistance in intertidal egg masses made by Haminoea vesicula, which preferentially attaches its flat, ribbon-shaped egg masses to submerged substrata. Egg masses occasionally detach and become stranded on exposed sand at low tide. Unlike adults, the encased embryos cannot avoid desiccation by selectively moving about the habitat, and the egg mass shape has high surface-area-to-volume ratio that should make it prone to drying out. Thus, I hypothesized that the embryos would not survive stranding. I tested this by deploying individual egg masses of two age classes on exposed sand bars for the duration of low tide. After rehydration, embryos midway through development showed higher rates of survival than newly-laid embryos, though for both stages survival rates over 25% were frequently observed. Laboratory desiccation trials showed that >75% survival is possible in an egg mass that has lost 65% of its water weight, and some survival (<25%) was observed even after 83% water weight lost. Although many surviving embryos in both experiments showed damage, these data demonstrate that egg mass stranding is not necessarily fatal to embryos. They may be able to survive a far greater range of conditions than they normally encounter, compensating for their lack of ability to move. Also, desiccation tolerance of embryos may reduce pressure on parents to find optimal laying substrata.

The third study takes a big-picture approach to investigating the evolution of different developmental strategies in cone snails, the largest genus of marine invertebrates. Cone snail species hatch out of their capsules as either swimming larvae or non-dispersing forms, and their developmental mode has direct consequences for biogeographic patterns. Variability in life history strategies among taxa may be influenced by biological, environmental, or phylogenetic factors, or a combination of these. While most prior research has examined these factors singularly, my aim was to investigate the effects of a host of intrinsic, extrinsic, and historical factors on two fundamental aspects of life history: egg size and egg number. I used phylogenetic generalized least-squares regression models to examine relationships between these two egg traits and a variety of hypothesized intrinsic and extrinsic variables. Adult shell morphology and spatial variability in productivity and salinity across a species geographic range had the strongest effects on egg diameter and number of eggs per capsule. Phylogeny had no significant influence. Developmental mode in Conus appears to be influenced mostly by species-level adaptations and niche specificity rather than phylogenetic conservatism. Patterns of egg size and egg number appear to reflect energetic tradeoffs with body size and specific morphologies as well as adaptations to variable environments. Overall, this series of studies highlights the importance of organism-scale biotic and abiotic interactions in evolutionary patterns.

Serotonin synthesis, release and reuptake in terminals: a mathematical model.

BACKGROUND: Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system. METHODS: We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data. RESULTS: We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct in silico experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to experimental data. Finally, we study how the properties of the the serotonin transporter and the autoreceptors give rise to the time courses of extracellular serotonin in various projection regions after a dose of fluoxetine. CONCLUSIONS: Serotonergic systems must respond robustly to important biological signals, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of the serotonin transporters and the serotonin autoreceptors. Many difficult questions remain in order to fully understand how serotonin biochemistry affects serotonin electrophysiology and vice versa, and how both are changed in the presence of selective serotonin reuptake inhibitors. Mathematical models are useful tools for investigating some of these questions.