The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

https://www.who.int/foodsafety/chem/2005_WHO_TEFs_ToxSci_2006.pdf

The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds.

介绍了Kirk—Othmer Encyclopedia of Chemical Technology（化工技术百科全书）（第五版）电子图书网络版数据库，并对该数据库使用方法和检索途径作出了说明，且结合实例简单地介绍了该数据库的检索方法。

Kirk-Othmer Encyclopedia of Chemical Technology数据库介绍及实例

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from...

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Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses

We present CasADi, an open-source software framework for numerical optimization. CasADi is a general-purpose tool that can be used to model and solve optimization problems with a large degree of flexibility, larger than what is associated with popular algebraic modeling languages such as AMPL, GAMS, JuMP or Pyomo. Of special interest are problems constrained by differential equations, i.e. optimal control problems. CasADi is written in self-contained C++, but is most conveniently used via full-featured interfaces to Python, MATLAB or Octave. Since its inception in late 2009, it has been used successfully for academic teaching as well as in applications from multiple fields, including process control, robotics and aerospace. This article gives an up-to-date and accessible introduction to the CasADi framework, which has undergone numerous design improvements over the last 7 years.

/pdf/casadi-a-software-framework-for-nonlinear-optimization-and-ddx9m9nls6.pdf

CasADi: a software framework for nonlinear optimization and optimal control

BackgroundIn recent decades, young men in some industrialized areas have reportedly experienced a decrease in semen quality.ObjectiveWe examined effects of perinatal dioxin exposure on sperm qualit...

Perinatal exposure to low doses of dioxin can permanently impair human semen quality.

In recent years the power systems research community has seen an explosion of work applying operations research techniques to challenging power network optimization problems. Regardless of the application under consideration, all of these works rely on power system test cases for evaluation and validation. However, many of the well established power system test cases were developed as far back as the 1960s with the aim of testing AC power flow algorithms. It is unclear if these power flow test cases are suitable for power system optimization studies. This report surveys all of the publicly available AC transmission system test cases, to the best of our knowledge, and assess their suitability for optimization tasks. It finds that many of the traditional test cases are missing key network operation constraints, such as line thermal limits and generator capability curves. To incorporate these missing constraints, data driven models are developed from a variety of publicly available data sources. The resulting extended test cases form a compressive archive, NESTA, for the evaluation and validation of power system optimization algorithms.

NESTA, The NICTA Energy System Test Case Archive

Although there has been nearly complete agreement in the scientific community that Monte Carlo techniques represent a significant improvement in the exposure assessment process, virtually all state and federal risk assessments still rely on the traditional point estimate approach. One of the rate-determining steps to a timely implementation of Monte Carlo techniques to regulatory decision making is the development of "standard" data distributions that are considered applicable to any setting. For many exposure variables, there is no need to wait any longer to adopt Monte Carlo techniques into regulatory policy since there is a wealth of data from which a robust distribution can be developed and ample evidence to indicate that the variable is not significantly influenced by site-specific conditions. In this paper, we propose several distributions that can be considered standard and customary for most settings. Age-specific distributions for soil ingestion rates, inhalation rates, body weights, skin surface area, tapwater and fish consumption, residential occupancy and occupational tenure, and soil-on-skin adherence were developed. For each distribution offered in this paper, we discuss the adequacy of the database, derivation of the distribution, and applicability of the distribution to various settings and conditions.

Recommended distributions for exposure factors frequently used in health risk assessment.

It has recently been suggested that "standard" data distributions for key exposure variables should be developed wherever appropriate for use in probabilistic or "Monte Carlo" exposure analyses. Soil-on-skin adherence estimates represent an ideal candidate for development of a standard data distribution: There are several readily available studies which offer a consistent pattern of reported results, and more importantly, soil adherence to skin is likely to vary little from site-to-site. In this paper, we thoroughly review each of the published soil adherence studies with respect to study design, sampling, and analytical methods, and level of confidence in the reported results. Based on these studies, probability density functions (PDF) of soil adherence values were examined for different age groups and different sampling techniques. The soil adherence PDF developed from adult data was found to resemble closely the soil adherence PDF based on child data in terms of both central tendency (mean = 0.49 and 0.63 mg-soil/cm2-skin, respectively) and 95th percentile values (1.6 and 2.4 mg-soil/cm2-skin, respectively). Accordingly, a single, "standard" PDF is presented based on all data collected for all age groups. This standard PDF is lognormally distributed; the arithmetic mean and standard deviation are 0.52 +/- 0.9 mg-soil/cm2-skin. Since our review of the literature indicates that soil adherence under environmental conditions will be minimally influenced by age, sex, soil type, or particle size, this PDF should be considered applicable to all settings. The 50th and 95th percentile values of the standard PDF (0.25 and 1.7 mg-soil/cm2-skin, respectively) are very similar to recent U.S. EPA estimates of "average" and "upper-bound" soil adherence (0.2 and 1.0 mg-soil/cm2-skin, respectively).

Development of a standard soil-to-skin adherence probability density function for use in Monte Carlo analyses of dermal exposure.

Shorter elimination half-lives for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) have been reported in human infants (Kreuzer et al. 1997; Leung et al. 2006) and in highly exposed adults (Aylward et al. 2005; Leung et al. 2005) compared with those in the general population. However, few published elimination half-life data are available for young children and adolescents 1–18 years of age. Needham et al. (1997/1998) presented TCDD decay curves for a 50-year-old Seveso male (initial TCDD concentration of 1,770 ppt) and a 6-year-old Seveso male (initial TCDD concentration of 15,900 ppt) and noted a much faster TCDD serum lipid decay for the child, especially over the 6-year period following exposure. Additional data on children are needed to further validate the two age-dependent PCDD/F half-life models that have been proposed for estimating childhood body burdens (Kerger et al. 2005; Kreuzer et al. 1997).

In this study we examined a database of longitudinal TCDD measurements in the blood lipids of children (ages 0.5–18 years) exposed during the 1976 trichlorophenol reactor explosion incident near Seveso, Italy. As many as 10 sequential measurements were made on some children. We evaluated changes in elimination rate of TCDD in blood lipids as influenced by age, latency from exposure, TCDD concentration or mass in the body, severity of chloracne, and body mass parameters potentially influencing the half-life in children, adolescents, and young adults. Our goal was to identify central tendency trends for the half-life versus age relationship that may be used to estimate childhood body burdens, particularly for children 1–7 years of age, an age range critical to understanding potential risks of PCDD/F intake during childhood (Kerger et al. 2005).

Paul Scott

Papers

Perinatal exposure to low doses of dioxin can permanently impair human semen quality.

NESTA, The NICTA Energy System Test Case Archive

Recommended distributions for exposure factors frequently used in health risk assessment.

Development of a standard soil-to-skin adherence probability density function for use in Monte Carlo analyses of dermal exposure.

Age- and concentration-dependent elimination half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Seveso children.