Issues Arising on the Interface of MPAs and Fisheries Management

One of 6 background papers presented at The Expert Workshop on Marine Protected Areas and Fisheries Management: Review of Issues and Considerations held in Rome from June 12-14, 2006. The workshop was a response to the FAO Committee on Fisheries' call for technical guidelines for marine protected areas (MPAs) to assist Members to establish representative networks of MPAs by 2012, as agreed at the World Summit on Sustainable Development. This paper focuses on three key themes. First, it highlights the commonalities between discussions of marine protected areas and of fisheries management, with emphasis on their mutual use of spatial measures and ecosystem approaches. Second, the paper draws on the other Background Papers prepared for the Workshop, as well as a range of additional literature, to produce a substantial compilation of issues and considerations relating to the development and implementation of MPAs, within a fisheries management context. The third key theme of the paper is a focus on the 'preliminary steps' of decision-making, in which scoping of needs, gaps and feasibility takes place from the dual perspectives of MPAs and fisheries management. A relative paucity of information and analysis on this topic is noted, along with a consequent need for additional work on the subject. An initial effort is undertaken to explore the key decision-making elements in this 'preliminary stage'

Doctor of Philosophy

dissertationInfertility is traditionally defined as failure to achieve pregnancy after 12 or more months of regular unprotected intercourse; an estimated 10-15% of women experience infertility at some point in their reproductive life. The majority of infertility research has been focused on couples actively seeking treatment in specialty clinics, overlooking individuals who are infertile but not seeking medical specialty treatment. This dissertation uses data from the Fertility Experiences to examine the complexities of infertility research, treatment and interventions, and outcomes. Aim 1 compares approaches to collecting information about pregnancy attempt duration and identifies predictors of misestimating time at risk for pregnancy when assessing duration using a single question compared to discrete date event histories. Aim 2 provides information on the use of interventions to enhance fertility over the course of the reproductive life. Aim 3 examines the association between infertility treatment (ovulation stimulation, intrauterine insemination (IUI), and in-vitro fertilization (IVF)) used during the cycle of conception and preterm birth (<37 weeks completed gestation) using subfertile women who conceived spontaneously, without medical treatment, as controls. Aim one found that two-thirds of women substantially misestimated their biological time at risk for pregnancy when asked a single question. Detailed attempt histories, capturing specific dates, can provide a more nuanced assessment of biological time at risk of pregnancy, duration of intentional pregnancy attempt, and specifically the number of cycles where fertility focused intercourse is being used to ensure appropriately timed intercourse. Aim two found that women commonly use both medical and nonmedical interventions while trying to conceive. Primary care clinicians and fertility specialists should assume that nearly all their patients are using some type of nonmedical intervention and should take a full history that includes assessment of behavioral changes and complementary and alternative medicine. Aim three found that all fertility treatments (ovulation drugs, IUI, and IVF) were associated with a higher incidence of preterm birth, predominantly related to multiple gestation births. The findings support the use of treatment protocols that maximize singleton gestation. In addition, the findings highlight the increased risk of preterm birth in pregnancies conceived using any medical fertility treatment, not just IVF

Molecular triggers of egg activation at fertilization in mammals

In mammals, the sperm activates the development of the egg by triggering a series of oscillations in the cytosolic-free Ca2+concentration (Ca2+i). The sperm triggers these cytosolic Ca2+ioscillations after sperm–egg membrane fusion, as well as after intracytoplasmic sperm injection (ICSI). These Ca2+ioscillations are triggered by a protein located inside the sperm. The identity of the sperm protein has been debated over many years, but all the repeatable data now suggest that it is phospholipase Czeta (PLCζ). The main downstream target of Ca2+ioscillations is calmodulin-dependent protein kinase II (CAMKII (CAMK2A)), which phosphorylates EMI2 and WEE1B to inactivate the M-phase promoting factor protein kinase activity (MPF) and this ultimately triggers meiotic resumption. A later decline in the activity of mitogen-activated protein kinase (MAPK) then leads to the completion of activation which is marked by the formation of pronuclei and entry into interphase of the first cell cycle. The early cytosolic Ca2+increases also trigger exocytosis via a mechanism that does not involve CAMKII. We discuss some recent developments in our understanding of these triggers for egg activation within the framework of cytosolic Ca2+signaling.</jats:p

Trading Pain for Gain: Addressing Misaligned Interests in Prescription Drug Benefit Administration

Over the last two decades, Pharmacy Benefit Managers (PBMs), organizations that act as middlemen between health plans and drug manufacturers, have become increasingly powerful players in the healthcare industry. PBMs promise to leverage their expertise and ability to aggregate buying power to negotiate lower drug prices and administer prescription drug benefit plans. In practice, however, PBMs are widely criticized for benefitting from, and contributing to, inefficiencies in the prescription drug market, particularly by imposing restrictions on beneficiary access to drugs in exchange for rebates paid to PBMs by manufacturers. To the extent that the rebates are retained by PBMs, or otherwise do not result in a benefit to the beneficiaries, this practice amounts to trading the pain of plan beneficiaries for the PBM’s own gain. Despite this criticism, regulatory and enforcement efforts directed against PBMs have been anemic. Existing structural and legal protections for beneficiaries are largely ineffectual. While this problem is widely acknowledged, regulators have failed to pass new laws that successfully address the challenges posed by the insertion of PBMs as middlemen into the web of prescription drug benefits and reimbursement. Regulators express frustration with the complexity of balancing the interests of beneficiaries with PBMs’ aspirational goal of cost-control, as well as with addressing the inherent conflict of interest in PBMs’ competing goals of profitability for themselves and cost containment for their clients. Lawsuits alleging PBM mistreatment of beneficiaries are sparse, and a consistent vision of what is and is not permissible to PBMs has not emerged from the case law. But the Federal Anti-Kickback Statute can—and there are indications that it increasingly will—be used to regulate manufacturer-PBM rebate arrangements. The U.S. Department of Justice recently settled a case predicated on an allegation that a pharmaceutical manufacturer, Roche, violated the Federal Anti-Kickback Statute when it paid a health insurance company, Humana, a kickback of lump sum debt forgiveness for formulary placement, conditioned on the exclusion of a competitor. Also, the federal government recently adopted a rule applicable to Medicare Part D plans that radically reconfigures the existing incentives by prohibiting manufacturers from extending rebates other than at the point of sale, and from making the rebates contingent on the plans or PBMs taking various steps with respect to encouragement of use of the drugs. These developments likely presage increased use of the Anti-Kickback Statute to attack rebating arrangements and underscore the need for PBMs to reevaluate their current practices with respect to their relationships with manufacturers to ensure that they are complying with the law. In this Article, we argue that the Federal Anti-Kickback Statute and its state law analogs, state anti-kickback statutes, can be used to effectively protect beneficiary interests against manufacturer-purchased, PBM-imposed restrictions on access to drugs. We also identify key issues that may be hampering effective enforcement, and suggest an analysis that effectively addresses these issues. We demonstrate that current law is best understood to allow manufacturers to extend discounts and rebates to plans (either directly or through PBMs) but not to PBMs, and that those rebates cannot make those payments contingent on PBMs or plans adopting specific preferences for drugs. By embracing these principles, PBMs can protect beneficiary interests, achieve enforcement certainty, and perhaps ward off the ultimate adoption of more radical restrictions

Isotopic (δ18O and δ2H) Integrity of Water Samples Collected and Stored by Automatic Samplers

Stable water isotopes are increasingly becoming part of routine monitoring programs that use automatic samplers. The objectives of this study were to quantify the uncertainty in isotope signatures due to the length of sample storage (1–24 d) inside autosamplers over a range of air temperatures (5–35°C) and to evaluate the effectiveness of two evaporation reduction measures (mineral oil and high density polyethylene balls). Results of the laboratory study showed that up to 11.8% of the sample volume evaporated when samples were stored in an autosampler at 35°C for 24 d. To prevent significant water isotope fractionation, samples should be retrieved from autosampler

PLCz induced Ca2+ oscillations in mouse eggs involve a positive feedback cycle of Ca2+ induced InsP3 formation from cytoplasmic PIP2

Egg activation at fertilization in mammalian eggs is caused by a series of transient increases in the cytosolic free Ca2+ concentration, referred to as Ca2+ oscillations. It is widely accepted that these Ca2+ oscillations are initiated by a sperm derived phospholipase C isoform, PLCζ that hydrolyses its substrate PIP2 to produce the Ca2+ releasing messenger InsP3. However, it is not clear whether PLCζ induced InsP3 formation is periodic or monotonic, and whether the PIP2 source for generating InsP3 from PLCζ is in the plasma membrane or the cytoplasm. In this study we have uncaged InsP3 at different points of the Ca2+ oscillation cycle to show that PLCζ causes Ca2+ oscillations by a mechanism which requires Ca2+ induced InsP3 formation. In contrast, incubation in Sr2+ media, which also induces Ca2+ oscillations in mouse eggs, sensitizes InsP3-induced Ca2+ release. We also show that the cytosolic level Ca2+ is a key factor in setting the frequency of Ca2+ oscillations since low concentrations of the Ca2+ pump inhibitor, thapsigargin, accelerates the frequency of PLCζ induced Ca2+ oscillations in eggs, even in Ca2+ free media. Given that Ca2+ induced InsP3 formation causes a rapid wave during each Ca2+ rise, we use a mathematical model to show that InsP3 generation, and hence PLCζ's substate PIP2, has to be finely distributed throughout the egg cytoplasm. Evidence for PIP2 distribution in vesicles throughout the egg cytoplasm is provided with a rhodamine-peptide probe, PBP10. The apparent level of PIP2 in such vesicles could be reduced by incubating eggs in the drug propranolol which also reversibly inhibited PLCζ induced, but not Sr2+ induced, Ca2+ oscillations. These data suggest that the cytosolic Ca2+ level, rather than Ca2+ store content, is a key variable in setting the pace of PLCζ induced Ca2+ oscillations in eggs, and they imply that InsP3 oscillates in synchrony with Ca2+ oscillations. Furthermore, they support the hypothesis that PLCζ and sperm induced Ca2+ oscillations in eggs requires the hydrolysis of PIP2 from finely spaced cytoplasmic vesicles

Proactive, Not Reactive: Evolving Elm Management in the Nation\u27s Capital

Washington D.C. is home to many historic elm corridors managed in close partnership between numerous urban forestry stakeholders. In recent years, the city\u27s elms have been used as part of streetscape revitalization initiatives due to their quick-growing nature. The use of a popular Ulmus americana cultivar, Princeton, has brought about notable challenges in urban tree management. From the nursery to the tree box and even ten years later, these elms have required consistent attention in order to adequately train the form to achieve a sustainable canopy while minimizing structural defects. Two such plantings are explored, both with hand-selected trees from the same stock and nursery. These serve to highlight the differences between traditional urban forestry plantings and those under constant and careful scrutiny