Species-specific patterns in bivalve larval supply to a coastal embayment

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution February 2011Larval supply is an important process linking reproductive output to recruitment of benthic marine invertebrates. Few species-specific studies of bivalve larvae have been performed due to the lack of suitable methods for species identification. This thesis focused on applying a method to identify larvae from field samples from Waquoit Bay, MA using shell birefringence patterns. This method was then used to address variability in larval supply for three bivalve species on weekly, tidal, and hourly scales. Sampling weekly for six months during two years showed large variability in larval concentrations on this time scale. Abundances of most species were related to bay temperature, and species distributions among sampling sites were indicative of transport potential and population coherence. Greater growth of larvae in 2009 compared to 2007 was attributed to more wind-induced mixing and better food availability in 2009. Integrative samples over each tidal event for a 14-day period demonstrated that larvae were mostly constrained by water masses. During a period when there were sharp tidal signals in temperature and salinity, larval concentrations were higher in bay water compared to coastal waters on incoming tides. After a storm event, water mass properties were less distinct between tidal events and a semidiurnal signal in larval concentrations was no longer apparent. The timing of periods of high larval concentrations did not always coincide with periods of highest water mass flux reducing net export in some cases. On an hourly scale, the vertical distribution of larvae affected by water column stratification and strength of tidal flow. Strong currents and a fresh upper layer both prevented larvae from concentrating at the surface. There was little evidence of peaks in larval concentrations associated with a given tidal period. Species-specific data can provide new perspectives on larval transport. For the three species studied, Anomia simplex, Guekensia demissa, and Mercenaria mercenaria, different source areas, patterns for growth, and potential for export were observed. Applying species-specific identification methods to future studies of bivalve larval transport has the potential to relate larval abundance to settlement patterns, an important component of larval ecology and shellfish management.Funding for this thesis research was provided by an award to from NOAA Sea Grant to S. Gallager (grant NA06OAR417002), an award to S. Gallager and C. Mingione Thompson from the Estuarine Reserves Division, Office of Ocean and Coastal Resource Management, National Ocean Service, National Oceanic and Atmospheric Administration (grant NA07NOS42000024), the WHOI Academic Programs Office, a WHOI Coastal Ocean Institute student grant, the WHOI Biology Department, and the WHOI Ocean Life Institute

Intrapartum epidural analgesia and breastfeeding: a prospective cohort study

BACKGROUND Anecdotal reports suggest that the addition of fentanyl (an opioid) to epidural analgesia for women during childbirth results in difficulty establishing breastfeeding. The aim of this paper is to determine any association between epidural analgesia and 1) breastfeeding in the first week postpartum and 2) breastfeeding cessation during the first 24 weeks postpartum. METHODS A prospective cohort study of 1280 women aged > or = 16 years, who gave birth to a single live infant in the Australian Capital Territory in 1997 was conducted. Women completed questionnaires at weeks 1, 8, 16 and 24 postpartum. Breastfeeding information was collected in each of the four surveys and women were categorised as either fully breastfeeding, partially breastfeeding or not breastfeeding at all. Women who had stopped breastfeeding since the previous survey were asked when they stopped. RESULTS In the first week postpartum, 93% of women were either fully or partially breastfeeding their baby and 60% were continuing to breastfeed at 24 weeks. Intrapartum analgesia and type of birth were associated with partial breastfeeding and breastfeeding difficulties in the first postpartum week (p < 0.0001). Analgesia, maternal age and education were associated with breastfeeding cessation in the first 24 weeks (p < 0.0001), with women who had epidurals being more likely to stop breastfeeding than women who used non-pharmacological methods of pain relief (adjusted hazard ratio 2.02, 95% CI 1.53, 2.67). CONCLUSION Women in this cohort who had epidurals were less likely to fully breastfeed their infant in the few days after birth and more likely to stop breastfeeding in the first 24 weeks. Although this relationship may not be causal, it is important that women at higher risk of breastfeeding cessation are provided with adequate breastfeeding assistance and support.Christine Roberts is supported by a National Health and Medical Research Council (NHMRC) of Australia Public Health Practitioner Fellowship and Siranda Torvaldsen is supported by a NHMRC Australian Research Training Fellowship. The cohort study was supported by a project grant from The Canberra Hospital Private Practice Fund. Additional funding was provided by The Canberra Hospital Auxiliary, the Nurses' Board of the Australian Capital Territory, and the Australian Capital Territory Department of Health & Community Care

Semi-automated image analysis for the identification of bivalve larvae from a Cape Cod estuary

Author Posting. © Association for the Sciences of Limnology and Oceanography, 2012. This article is posted here by permission of Association for the Sciences of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography: Methods 10 (2012): 538-554, doi:10.4319/lom.2012.10.538.Machine-learning methods for identifying planktonic organisms are becoming well-established. Although similar morphologies among species make traditional image identification methods difficult for larval bivalves, species-specific shell birefringence patterns under polarized light permit identification by color and texture-based features. This approach uses cross-polarized images of bivalve larvae, extracts Gabor and color angle features from each image, and classifies images using a Support Vector Machine. We adapted this method, which was established on hatchery-reared larvae, to identify bivalve larvae from a series of field samples from a Cape Cod estuary in 2009. This method had 98% identification accuracy for four hatchery-reared species. We used a multiplex polymerase chain reaction (PCR) method to confirm field identifications and to compare accuracies to the software classifications. Image classification of larvae collected in the field had lower accuracies than both the classification of hatchery species and PCR-based identification due to error in visually classifying unknown larvae and variability in larval images from the field. A six-species field training set had the best correspondence to our visual classifications with 75% overall agreement and individual species agreements from 63% to 88%. Larval abundance estimates for a time-series of field samples showed good correspondence with visual methods after correction. Overall, this approach represents a cost- and time-saving alternative to molecular-based identifications and can produce sufficient results to address long-term abundance and transport-based questions on a species-specific level, a rarity in studies of bivalve larvae.This project was supported by an award to S. Gallager and C. Mingione Thompson from the Estuarine Reserves Division, Office of Ocean and Coastal Resource Management, National Ocean Service, National Oceanic and Atmospheric Administration and a grant from Woods Hole Oceanographic Institution’s Coastal Ocean Institute

Species-specific abundance of bivalve larvae in relation to biological and physical conditions in a Cape Cod estuary : Waquoit Bay, Massachusetts (USA)

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Inter-Research for personal use, not for redistribution. The definitive version was published in Marine Ecology Progress Series 469 (2012): 53-69, doi:10.3354/meps09998.Physical and biological conditions impact recruitment and adult population structure of 34 marine invertebrates by affecting early life history processes from spawning to post-settlement. We investigated how temperature, salinity and phytoplankton influenced larval abundance and larval size structure for three species of bivalves over two non-consecutive years in Waquoit Bay, MA. Abundance and size of Mercenaria mercenaria (quahog), Anomia simplex (jingle clam), and Geukensia demissa (ribbed mussel) larvae were compared between locations in the bay and with environmental conditions. Shell birefringence patterns using polarized light microscopy were used to distinguish species. Larval abundances for all three species were higher in 2009 than in 2007 and were positively correlated with temperature in both years. Differences in larval abundance and size structure between bay sites were attributed to salinity tolerances and potential source locations. Higher survival in 2009 than in 2007, as determined by number of pediveligers, was likely due to higher temperatures and greater food availability during the peak abundance months of July and August in 2009. Yearly differences in larval growth and survival can have a large impact on recruitment. Knowing the optimal periods and locations for larval abundance and survival can be useful for isolating species-specific patterns in larval dispersal and to aid resource managers in enhancing or restoring depleted populations.This research was conducted in the National Estuarine Research Reserve System under an award to S. Gallager and C. Mingione Thompson from the Estuarine Reserves Division, Office of Ocean and Coastal Resource Management, National Ocean Service, National Oceanic and Atmospheric Administration

Acute effects of elevated NEFA on vascular function: a comparison of SFA and MUFA

There is emerging evidence to show that high levels of NEFA contribute to endothelial dysfunction and impaired insulin sensitivity. However, the impact of NEFA composition remains unclear. A total of ten healthy men consumed test drinks containing 50 g of palm stearin (rich in SFA) or high-oleic sunflower oil (rich in MUFA) on separate occasions; a third day included no fat as a control. The fats were emulsified into chocolate drinks and given as a bolus (approximately 10 g fat) at baseline followed by smaller amounts (approximately 3 g fat) every 30 min throughout the 6 h study day. An intravenous heparin infusion was initiated 2 h after the bolus, which resulted in a three- to fourfold increase in circulating NEFA level from baseline. Mean arterial stiffness as measured by digital volume pulse was higher during the consumption of SFA (P,0·001) but not MUFA (P¼0·089) compared with the control. Overall insulin and gastric inhibitory peptide response was greater during the consumption of both fats compared with the control (P,0·001); there was a second insulin peak in response to MUFA unlike SFA. Consumption of SFA resulted in higher levels of soluble intercellular adhesion molecule-1 (sI-CAM) at 330 min than that of MUFA or control (P#0·048). There was no effect of the test drinks on glucose, total nitrite, plasminogen activator inhibitor-1 or endothelin-1 concentrations. The present study indicates a potential negative impact of elevated NEFA derived from the consumption of SFA on arterial stiffness and sI-CAM levels. More studies are needed to fully investigate the impact of NEFA composition on risk factors for CVD

Decitabine-Vorinostat combination treatment in acute myeloid leukemia activates pathways with potential for novel triple therapy

Despite advancements in cancer therapeutics, acute myeloid leukemia patients over 60 years old have a 5-year survival rate of less than 8%. In an attempt to improve this, epigenetic modifying agents have been combined as therapies in clinical studies. In particular combinations with Decitabine and Vorinostat have had varying degrees of efficacy. This study therefore aimed to understand the underlying molecular mechanisms of these agents to identify potential rational epi-sensitized combinations. Combined Decitabine-Vorinostat treatment synergistically decreased cell proliferation, induced apoptosis, enhanced acetylation of histones and further decreased DNMT1 protein with HL-60 cells showing a greater sensitivity to the combined treatment than OCI-AML3. Combination therapy led to reprogramming of unique target genes including AXL, a receptor tyrosine kinase associated with cell survival and a poor prognosis in AML, which was significantly upregulated following treatment. Therefore targeting AXL following epi-sensitization with Decitabine and Vorinostat may be a suitable triple combination. To test this, cells were treated with a novel triple combination therapy including BGB324, an AXL specific inhibitor. Triple combination increased the sensitivity of OCI-AML3 cells to Decitabine and Vorinostat as shown through viability assays and significantly extended the survival of mice transplanted with pretreated OCI-AML3 cells, while bioluminescence imaging showed the decrease in disease burden following triple combination treatment. Further investigation is required to optimize this triple combination, however, these results suggest that AXL is a potential marker of response to Decitabine-Vorinostat combination treatment and offers a new avenue of epigenetic combination therapies for acute myeloid leukemia

Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study

Objectives The interleukin-6 receptor (IL-6R) blocker tocilizumab (TCZ) reduces inflammatory disease activity in rheumatoid arthritis (RA) but elevates lipid concentrations in some patients. We aimed to characterise the impact of IL-6R inhibition on established and novel risk factors in active RA. Methods Randomised, multicentre, two-part, phase III trial (24-week double-blind, 80-week open-label), MEASURE, evaluated lipid and lipoprotein levels, high-density lipoprotein (HDL) particle composition, markers of coagulation, thrombosis and vascular function by pulse wave velocity (PWV) in 132 patients with RA who received TCZ or placebo. Results Median total-cholesterol, low-density lipoprotein-cholesterol (LDL-C) and triglyceride levels increased in TCZ versus placebo recipients by week 12 (12.6% vs 1.7%, 28.1% vs 2.2%, 10.6% vs −1.9%, respectively; all p&#60;0.01). There were no significant differences in mean small LDL, mean oxidised LDL or total HDL-C concentrations. However, HDL-associated serum amyloid A content decreased in TCZ recipients. TCZ also induced reductions (&#60;30%) in secretory phospholipase A2-IIA, lipoprotein(a), fibrinogen and D-dimers and elevation of paraoxonase (all p&#60;0.0001 vs placebo). The ApoB/ApoA1 ratio remained stable over time in both groups. PWV decreases were greater with placebo than TCZ at 12 weeks (adjusted mean difference 0.79 m/s (95% CI 0.22 to 1.35; p=0.0067)). Conclusions These data provide the first detailed evidence for the modulation of lipoprotein particles and other surrogates of vascular risk with IL-6R inhibition. When compared with placebo, TCZ induced elevations in LDL-C but altered HDL particles towards an anti-inflammatory composition and favourably modified most, but not all, measured vascular risk surrogates. The net effect of such changes for cardiovascular risk requires determination.</p

The validity and responsiveness of three quality of life measures in the assessment of psoriasis patients: results of a phase II study

BACKGROUND: Patient-reported outcome (PROs) measures are being used more frequently in investigational studies of treatments for moderate to severe plaque psoriasis. The objective of this study was to examine the relationships among the Dermatology Life Quality Index (DLQI), the Short Form 36 (SF-36), and the EuroQOL 5D (EQ-5D) and to assess their validity, responsiveness, and estimates of minimum important differences. METHODS: A Phase II, randomized, double-blind, parallel group, placebo-controlled, multi-center clinical trial assessed the clinical efficacy and safety of two doses of subcutaneously administered adalimumab vs. placebo for 12 weeks in the treatment of 147 patients with moderate to severe plaque psoriasis. This study provided the opportunity to evaluate the validity and responsiveness to change in clinical status of PROs instruments. Patients completed the DLQI, SF-36, and EQ-5D questionnaires at baseline and at 12 weeks. Blinded investigators assessed the Psoriasis Area and Severity Index (PASI) scores and the Physician's Global Assessment (PGA) scores of enrolled patients. The responsiveness of the measures to changes in the clinical endpoints from baseline to Week 12 was assessed. Estimates of minimum important differences (MID) were derived. All analyses were performed with blinded data; findings and conclusions were not biased based on treatment condition. RESULTS: The dermatology-specific DLQI was highly correlated to clinical endpoints at baseline and at Week 12, and was the most responsive PRO to changes in endpoints. Compared with the SF-36, the EQ-5D index score and VAS scores were generally more highly correlated with clinical endpoints, but displayed about the same degree of responsiveness. The most responsive SF-36 scales were the Bodily Pain and Social Functioning scales. Estimates of the MID for the DLQI ranged from 2.3–5.7 and for the SF-36 Physical Component Summary (PCS) score ranged from 2.5–3.9. CONCLUSION: This study provides support for the continued use of the DLQI and SF-36 PCS in the assessment of treatments for psoriasis. On the basis of the results from this trial, the EQ-5D should be considered as a general PRO measure in future clinical trials of patients with moderate to severe plaque psoriasis

Book Reviews

Critical Thinking and Intelligence Analysis. By David T.Moore. At The Center Of The Storm: The CIA During America\u27s Time of Crisis. By George Tenet with Bill Harlow. Female Suicide Bombers. By Rosemarie Skaine. Information Operations: Doctrine and Practice. By Christopher Paul. The Secret Sentry: The Untold History of the National Security Agency. By Matthew M. Aid. The Blood of Lambs: A Former Terrorist\u27s Memoir of Death and Redemption. By Kamal Saleem with Lynn Vincent. Attaché Extraordinaire: Vernon A. Walters in Brazil. By Frank Márcio De Oliveira