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Journal of Happiness Studies | 2000

Global Progress II: Evolutionary Mechanisms and their Side-effects

Francis Heylighen; Jan L. Bernheim

This paper attempts to update the 18th century concept of progress by an evolutionary theoretical framework, while replying to some of the contemporary critiques. Progress, understood as increase in fitness (or its proxy, quality of life) necessarily accompanies evolution by natural selection. In socio-cultural evolution, this mechanism is reinforced by growth of knowledge and virtuous cycles, but can be accompanied by negative side-effects such as overshooting and parasitism. The most pressing of the contemporary side-effects, such as pollution and the increased pace of life, are discussed, but it is concluded that they can be tackled without really endangering global progress. The anxiety that they engender is unfortunately amplified by a “bad news” bias in the media, leading to an inappropriately pessimistic view of the situation by the public.


Cell Proliferation | 1978

Quantification of entry into and exit from the cell cycle in human lymphocyte cultures.

Randel Dorian; Jan L. Bernheim; J. Mendelsohn

A mathematical model is presented for the analysis of transition between cycling and non‐cycling compartments by cells responding to a growth stimulus. the cellular age distribution as a function of time is derived from sequential [3H]thymidine pulse labeling indices. Rates of entry into and exit from the cycling compartment are determined on the basis of labeling indices obtained after instantaneous and long duration [3H]thymidine pulses. Analysis of an experiment involving sequential measurements over the whole lifespan of a human lymphocyte culture stimulated by phytohemagglutinin is presented as an example of the application of this method.


Regulatory Mechanisms in Lymphocyte Activation | 1977

KINETICS OF DNA SYNTHESIS AND CELL PROLIFERATION IN LYMPHOCYTE ACTIVATION: WORKSHOP REVIEW

Jan L. Bernheim; John Mendelsohn

Publisher Summary This chapter presents a summary of the workshop organized successively at the Third European Immunology Meeting (Copenhagen, August 23–26, 1976) and at the Eleventh Leukocyte Culture Conference . The workshop addressed the following topics: (1) culture circumstances that best promote lymphocyte transformation and proliferation, (2) kinetics of proliferation in response to antigens and mitogens, (3) the reliable quantitative assay methods for in vitro lymphocyte proliferation, and (4) solid information that exists on three categories of lymphocyte DNA with unusual or apparently specific characteristics. This chapter reviews various studies on this subject into context. The workshop focused on two highly relevant aspects of the lymphocyte response to stimulation, namely, initiation and termination of proliferation.


Fundamental & Clinical Pharmacology | 1995

Similia similibus obscurantur: the pharmacological clinical activity bias I. A prototype model to correct a disease‐drug interaction leading to misestimations of drug‐attributable side effects

Jan L. Bernheim; I. Vrana

Summary— Drugs have side effects that manifest as signs or symptoms which are sometimes undistinguishable from signs or symptoms of active disease. The conventional approximation of the rate of side effects of drugs is by subtracting the rate of signs and symptoms in the placebo group from that in the drug group. This measures net side effects and is adequate in studies with healthy volunteers, in which no interaction between drug and disease exists. For ethical and practical reasons, however, volunteer studies cannot be large and the frequency of non‐rare side effects must be estimated in large‐scale clinical trials. In the latter, biasing drug disease interactions may occur. We report on such a hitherto undescribed interaction: the pharmacological clinical activity bias. If one is interested in estimating not the net, but the direct or intrinsic, ie, drug‐attributable side effects, the conventional approximation is biased whenever, in clinical trials, both of two conditions apply. The first is that the variable on the scale of which a sign or symptom is recorded as a putative side effect, is also in the absence of drug affected by uncontrolled disease. The second is that the drug has pharmacological clinical activity (A) on that sign or symptom, thus reducing the contribution of disease (D) to what is measured. In this case the drug affects the variable under study both directly, through its intrinsic side effect, and indirectly, through its clinical activity, and the rate of attributable side effects differs from the rate of net side effects as calculated by the conventional approximation. We present a simple deterministic model, which assumes that disease remains stable if untreated, additivity of the relative contributions of drug, placebo and disease to the total rate of the sign or symptom, and no other interaction between intrinsic properties of the drug and active disease than pharmacological clinical activity. This theoretical model quantifies the bias as D0(Ad ‐ Ap), in which D0 is the baseline frequency of the sign or symptom in the studied patients, and Ad and Ap are the intrinsic clinical activities of drug and placebo, respectively, on the sign or symptom under study. The model confirms that the conventional approximation of drug side effects is unbiased only in healthy volunteers or with drugs devoid of clinical activity. Without correction by such a model, any clinical activity of the drug or manifestation of active disease will cause the conventional approximation of side effects to be biased. This may manifest as artifacts such as attribution of a side effect when there is none, and as under‐ or overestimation, pseudo‐ tachyphylaxis, or pseudo‐delayedness of attributable side effects.


Regulatory Mechanisms in Lymphocyte Activation | 1977

IS THERE GENE AMPLIFICATION OR OTHER NONDUPLICATIVE DNA SYNTHESIS IN HUMAN LYMPHOCYTE ACTIVATION

John Mendelsohn; Randel Dorian; Jan Castagnola; Jan L. Bernheim

Publisher Summary This chapter presents a few studies in which highly purified human peripheral lymphocytes were incubated in MEM containing 10% autologous serum, glutamine, and antibiotics, in the presence of optimal concentrations of phytohemagglutinin. Cultures were incubated at an initial cell concentration of 2 × 105 lymphocytes/ml, which is one log below the widely used concentration. Under these conditions, up to a fivefold increase in cell number was observed over a period of 7 days. DNA purified from cultures labeled with 5-bromodeoxyuridine between days 3 and 4 for 24 h, a period longer than one mean cycle time, was analyzed on cesium chloride equilibrium density gradients: the percentages of DNA in the heavy–heavy, heavy–light, and light–light regions were, respectively, 19, 56, and 25, providing direct evidence for replication of more than 50% of the DNA and reentry of some cells into a second proliferative cycle.


Regulatory Mechanisms in Lymphocyte Activation | 1977

PITFALLS IN THE LYMPHOCYTE PROLIFERATION ASSAY: VARIATIONS IN PROLIFERATION KINETICS AND COLD THYMIDINE POOLS

Jan L. Bernheim; Randel Dorian; John Mendelsohn

Publisher Summary This chapter explores the variations in proliferation kinetics and cold thymidine pools. In a study described in the chapter, purified human peripheral blood lymphocytes were isolated, cultured, and PHA-stimulated. The use of an optimal dose of 1 μg/ml purified PHA, with low agglutinating potency, allowed accurate hemacytometer counting. DNA synthesis was assayed after 3H-TdR labeling (2 h, 2 μCi/ml, 6 Ci/mM) by autoradiography and liquid scintillation counting. The chapter presents two representative experiments that demonstrated a second difference between crowded and dilute PHA-stimulated cultures: variability in the kinetics of entry into proliferation. In the first experiment, a comparison of the fraction of cells labeled shows that the rates of entry into proliferation are similar for the two cell concentrations during the first 72 h. Thereafter, proliferation decreases in the crowded culture, whereas in the dilute culture, growth proceeds. The second experiment differs in that the entry into proliferation occurs more rapidly in the crowded culture. This would be expected if the cells produced additional recruitment activity that reached an effective level earlier in the concentrated than in the dilute cultures. In several such experiments described in the chapter, the kinetics of entry into proliferation varied unpredictably.


Bioethics | 1999

How to Get Serious Answers to the Serious Question: 'How have you been?': Subjective Quality of Life (QOL) as an Individual Experiential Emergent Construct

Jan L. Bernheim


Journal of Immunology | 1978

DNA synthesis and proliferation of human lymphocytes in vitro. I. Cell kinetics of response to phytohemagglutinin.

Jan L. Bernheim; Randel Dorian; John Mendelsohn


Proceedings of the National Academy of Sciences of the United States of America | 1977

Kinetics of cell death and disintegration in human lymphocyte cultures

Jan L. Bernheim; J. Mendelsohn; M. Kelley; Randel Dorian


Archive | 2000

Global Progress I: empirical evidence for increasing quality of life

Francis Heylighen; Jan L. Bernheim

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Randel Dorian

University of California

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M. Kelley

University of California

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Francis Heylighen

Vrije Universiteit Brussel

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Jan Castagnola

University of California

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M. Djobadze

University of California

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I. Vrana

University of Agriculture

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