Effect of Waste Discharges into a Silt-laden Estuary: A Case Study of Cook Inlet, Alaska

Cook Inlet is not well known. Although its thirty-foot tidal range is widely appreciated, its other characteristics, such as turbulence, horizontal velocities of flow, suspended sediment loads, natural biological productivity, the effects of fresh water inflows, temperature, and wind stresses, are seldom acknowledged. The fact that the Inlet has not been used for recreation nor for significant commercial activity explains why the average person is not more aware of these characteristics. Because of the gray cast created by the suspended sediments in the summer and the ice floes in the winter, the Inlet does not have the aura of a beautiful bay or fjord. The shoreline is inhospitable for parks and development, the currents too strong for recreational activities, and, because of the high silt concentration, there is little fishing. Yet, Cook Inlet, for all its negative attributes, can in no way be considered an unlimited dumping ground for the wastes of man. It may be better suited for this purpose than many bays in North America, but it does have a finite capacity for receiving wastes without unduly disturbing natural conditions. This report was written for the interested layman by engineers and scientists who tried to present some highly technical information in such a manner that it could be understood by environmentalists, concerned citizens, students, decision makers, and lawmakers alike. In attempting to address such a diverse audience, we risked failing to be completely understood by any one group. However, all too often research results are written solely for other researchers, a practice which leads to the advancement of knowledge but not necessarily to its immediate use by practicing engineers nor to its inclusion in social, economic, and political decision-making processes. We hope this report will shorten the usual time lag between the acquisition of new information and its use. Several additional reports will be available for a limited distribution. These will be directed to technicians who wish to know the mathematical derivations, assumptions, and other scientific details used in the study. Technical papers by the individual authors, published in national and international scientific and engineering journals, are also anticipated.The work upon which this report is based was supported in part by funds (Proj. B-015-ALAS) provided by the United States Department of the Interior, Office of Water Resources Research, as authorized under the Water Resources Act of 1964, as amended

The Value of Health and Longevity

We develop an economic framework for valuing improvements to health and life expectancy, based on individuals' willingness to pay. We then apply the framework to past and prospective reductions in mortality risks, both overall and for specific life-threatening diseases. We calculate (i) the social values of increased longevity for men and women over the 20th century; (ii) the social value of progress against various diseases after 1970; and (iii) the social value of potential future progress against various major categories of disease. The historical gains from increased longevity have been enormous. Over the 20th century, cumulative gains in life expectancy were worth over $1.2 million per person for both men and women. Between 1970 and 2000 increased longevity added about$3.2 trillion per year to national wealth, an uncounted value equal to about half of average annual GDP over the period. Reduced mortality from heart disease alone has increased the value of life by about $1.5 trillion per year since 1970. The potential gains from future innovations in health care are also extremely large. Even a modest 1 percent reduction in cancer mortality would be worth nearly$500 billion.

Current Unemployment, Historically Contemplated

macroeconomics, Current Unemployment

Regularized parametric system identification: a decision-theoretic formulation

Parametric prediction error methods constitute a classical approach to the identification of linear dynamic systems with excellent large-sample properties. A more recent regularized approach, inspired by machine learning and Bayesian methods, has also gained attention. Methods based on this approach estimate the system impulse response with excellent small-sample properties. In several applications, however, it is desirable to obtain a compact representation of the system in the form of a parametric model. By viewing the identification of such models as a decision, we develop a decision-theoretic formulation of the parametric system identification problem that bridges the gap between the classical and regularized approaches above. Using the output-error model class as an illustration, we show that this decision-theoretic approach leads to a regularized method that is robust to small sample-sizes as well as overparameterization.Comment: 10 pages, 8 figure

Characterizing the Dysfunctional NK Cell: Assessing the Clinical Relevance of Exhaustion, Anergy, and Senescence.

There is a growing body of literature demonstrating the importance of T cell exhaustion in regulating and shaping immune responses to pathogens and cancer. Simultaneously, the parallel development of therapeutic antibodies targeting inhibitory molecules associated with immune exhaustion (such as PD-1, but also TIGIT, and LAG-3) has led to a revolution in oncology with dramatic benefits in a growing list of solid and hematologic malignancies. Given this success in reinvigorating exhausted T cells and the related anti-tumor effects, there are increasing efforts to apply immune checkpoint blockade to other exhausted immune cells beyond T cells. One approach involves the reinvigoration of "exhausted" NK cells, a non-T, non-B lymphoid cell of the innate immune system. However, in contrast to the more well-defined and established molecular, genetic, and immunophenotypic characteristics of T cell exhaustion, a consensus on the defining functional and phenotypic features of NK "exhaustion" is less clear. As is well-known from T cell biology, separate and distinct molecular and cellular processes including senescence, anergy and exhaustion can lead to diminished immune effector function with different implications for immune regulation and recovery. For NK cells, it is unclear if exhaustion, anergy, and senescence entail separate and distinct entities of dysfunction, though all are typically characterized by decreased effector function or proliferation. In this review, we seek to define these distinct spheres of NK cell dysfunction, analyzing how they have been shown to impact NK biology and clinical applications, and ultimately highlight key characteristics in NK cell function, particularly in relation to the role of "exhaustion.