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At least 847 records · Page 47Linked to original sources
PubMed1995

Rational non-interventional paternalism: why doctors ought to make judgments of what is best for their patients.

This paper argues that doctors ought to make all things considered value judgments about what is best for their patients. It illustrates some of the shortcomings of the model of doctor as 'fact-provider'. The 'fact-provider' model fails to take account of the fact that practising medicine necessarily involves making value judgments; that medical practice is a moral practice and requires that doctors reflect on what ought to be done, and that patients can make choices which fail to express their autonomy and which are based on mistaken judgments of value. If doctors are properly to respect patient autonomy and to function as moral agents, they must make evaluations of what their patients ought to do, all things considered. This paper argues for 'rational, non-interventional paternalism'. This is a practice in which doctors form conceptions of what is best for their patients and argue rationally with them. It differs from old-style paternalism in that it is not committed to doing what is best.

Choice Behavior↗
PubMed1998

Bioethics of the refusal of blood by Jehovah's Witnesses: Part 2. A novel approach based on rational non-interventional paternalism.

Most physicians dealing with Jehovah's Witnesses (JWs) who refuse blood-based treatment are uncertain as to any obligation to educate patients where it concerns the JW blood doctrine itself. They often feel they must unquestioningly comply when demands are framed as religiously based. Recent discussion by dissidents and reformers of morally questionable policies by the JW organisation raise ethical dilemmas about "passive" support of this doctrine by some concerned physicians. In this paper, Part 2, I propose that physicians discuss the misinformation and irrationality behind the blood doctrine with the JW patient by raising questions that provide new perspectives. A meeting should be held non-coercively and in strict confidence, and the patient's decision after the meeting should be fully honoured (non-interventional). A rational deliberation based on new information and a new perspective would enable a certain segment of JW patients to make truly informed, autonomous and rational decisions.

Blood Transfusion↗
PubMed2001

Modelling and prediction for chaotic fir laser attractor using rational function neural network.

Many real-world systems such as irregular ECG signal, volatility of currency exchange rate and heated fluid reaction exhibit highly complex nonlinear characteristic known as chaos. These chaotic systems cannot be retreated satisfactorily using linear system theory due to its high dimensionality and irregularity. This research focuses on prediction and modelling of chaotic FIR (Far InfraRed) laser system for which the underlying equations are not given. This paper proposed a method for prediction and modelling a chaotic FIR laser time series using rational function neural network. Three network architectures, TDNN (Time Delayed Neural Network), RBF (radial basis function) network and the RF (rational function) network, are also presented. Comparisons between these networks performance show the improvements introduced by the RF network in terms of a decrement in network complexity and better ability of predictability.

Infrared Rays↗
PubMed2005

Understanding presentation of viral antigens to CD8+ T cells in vivo: the key to rational vaccine design.

CD8+ T cells play a critical role in antiviral immunity by exerting direct antiviral activity against infected cells. Because of their ability to recognize all types of viral proteins, they offer the promise of providing broad immunity to viruses that evade humoral immunity by varying their surface proteins. Consequently, there is considerable interest in developing vaccines that elicit effective antiviral T(CD8+) responses. Generating optimal vaccines ultimately requires rational design based on detailed knowledge of how T(CD8+) are activated in vivo under natural circumstances. Here we review recent progress obtained largely by in vivo studies in mice to understand the mechanistic basis for activation of naive T(CD8+) in virus infections. These studies point the way to detailed understanding and provide some key information for vaccine development, although much remains to be learned to enable truly rational vaccine design.

Animals↗
PubMed2005

Identification of an inactivating cysteine switch in protein kinase Cepsilon, a rational target for the design of protein kinase Cepsilon-inhibitory cancer therapeutics.

Critical roles played by some protein kinases in neoplastic transformation and progression provide a rationale for developing selective, small-molecule kinase inhibitors as antineoplastic drugs. Protein kinase Cepsilon (PKCepsilon) is a rational target for cancer therapy, because it is oncogenic and prometastatic in transgenic mouse models. PKCepsilon is activated by sn-1,2-diacylglycerol (DAG). Attempts to develop selective PKCepsilon inhibitors that block activation by DAG or compete with ATP have not yet met with success, suggesting a need for new strategies. We previously reported that cystamine and a metabolic cystine precursor inactivate PKCepsilon in cells in a thiol-reversible manner. In this report, we first determined that PKCepsilon became resistant to inactivation by disulfides when Cys452 was replaced with alanine by site-specific mutagenesis of human PKCepsilon or a constitutively active PKCepsilon mutant. These results showed that the disulfides inactivated PKCepsilon by thiol-disulfide exchange, either upon Cys452 S-thiolation or by rearrangement to an intra-protein disulfide. Mass spectrometric analysis of peptide digests of cystamine-inactivated, carbamidomethylated PKCepsilon detected a peptide S-cysteaminylated at Cys452, indicating that Cys452 S-cysteaminylation is a stable modification. Furthermore, PKCepsilon inactivation by N-ethylmaleimide was Cys452 dependent, providing corroborative evidence that PKCepsilon inhibitors can be designed by targeting Cys452 with small molecules that stably modify the residue. Cys452 is an active site residue that is conserved in only 11 human protein kinase genes. Therefore, the PKCepsilon-inactivating Cys452 switch is a rational target for the design of antineoplastic drugs that selectively inhibit PKCepsilon.

Amino Acid Sequence↗
PubMed2001

Understanding heroin as a "rational addiction".

This paper makes some interpretations on the Becker and Murphy model of rational addiction so as to consider policy issues beyond the discussion of the effects of price on heroin consumption. Through the model of the rational heroin user, this paper argues that heroin use is a symptom of other factors. The focus of the analysis is placed on the negative life events that underpin heroin consumption. Thus, policy makers who want to stop heroin use may find it more effective to first stop the underlying problems that are the cause of the catalytic consumption of heroin use. It may prove better to promote other religious, family and educational activities than to actively discourage heroin use.

Crime↗
PubMed1983

Rational basis for the use of sleeping pills.

The diagnosis and treatment of insomnia is a major clinical issue. This is because the complaint of insomnia is highly prevalent and because the various clinical and laboratory manifestations of insomnia are complex. In addition, insomnia involves both day and night. This paper attempts to provide a rational framework for the evaluation of insomnia and the use of sleeping pills. Insomnia is defined and described with special attention to differentiating the subjective complaint and the laboratory assessment of objective sleep parameters. Specific disorders causing or associated with sleep disturbance and the complaint of insomnia are described, and some data bearing on relative prevalence of specific disorders are presented. Consideration of sleeping pills involves the evaluation of hypnotic efficacy as a property of the medication on the one hand and the practical clinical application on the other. Properties of different hypnotics are reviewed, including factors that affect the use of hypnotics in clinical practice. It is concluded that the rational use of sleeping pills demands a systematic approach to the evaluation of the individual patient and a specific attempt to formulate individual treatment goals together with a knowledgeable consideration of the specific chemotherapeutic agent to be utilized.

Anxiety↗
PubMedDate not supplied

Rational and irrational clinical strategies for collaborative medicine.

Individual practitioners and health care systems/organizations increasingly understand the rationale for collaborative medicine. An absence of collaboration can compromise the quality and safety of patient care. But having a rationale to provide collaborative medicine without also having a rational clinical strategy can be equally compromising to the quality and safety of patient care. Reasonable evidentiary criteria must be used to determine whether specific therapies merit inclusion or exclusion in a collaborative medicine model. Ranking therapies hierarchically on the basis of their risk-benefit ratio simplifies matching of therapies with the needs of the patient. A unifying taxonomy that categorizes all therapies (complementary/alternative and conventional) on the basis of how we think they work (presumed mechanisms of action) facilitates development of a clinical strategy for collaborative medicine. On the basis of these principles, a rational clinical strategy for collaborative medicine is described to help optimize the quality and safety of patient care.

Attitude of Health Personnel↗
PubMed2005

Rational polynomial representation of ribonucleotide reductase activity.

BACKGROUND: Recent data suggest that ribonucleotide reductase (RNR) exists not only as a heterodimer R12R22 of R12 and R22 homodimers, but also as tetramers R14R24 and hexamers R16R26. Recent data also suggest that ATP binds the R1 subunit at a previously undescribed hexamerization site, in addition to its binding to previously described dimerization and tetramerization sites. Thus, the current view is that R1 has four NDP substrate binding possibilities, four dimerization site binding possibilities (dATP, ATP, dGTP, or dTTP), two tetramerization site binding possibilities (dATP or ATP), and one hexamerization site binding possibility (ATP), in addition to possibilities of unbound site states. This large number of internal R1 states implies an even larger number of quaternary states. A mathematical model of RNR activity which explicitly represents the states of R1 currently exists, but it is complicated in several ways: (1) it includes up to six-fold nested sums; (2) it uses different mathematical structures under different substrate-modulator conditions; and (3) it requires root solutions of high order polynomials to determine R1 proportions in mono-, di-, tetra- and hexamer states and thus RNR activity as a function of modulator and total R1 concentrations. RESULTS: We present four (one for each NDP) rational polynomial models of RNR activity as a function of substrate and reaction rate modifier concentrations. The new models avoid the complications of the earlier model without compromising curve fits to recent data. CONCLUSION: Compared to the earlier model of recent data, the new rational polynomial models are simpler, adequately fitting, and likely better suited for biochemical network simulations.

Enzyme Activation↗
PubMed2004

A rational treatment of Mendelian genetics.

BACKGROUND: The key to a rational treatment of elementary Mendelian genetics, specifically to an understanding of the origin of dominant and recessive traits, lies in the facts that: (1) alleles of genes encode polypeptides; (2) most polypeptides are catalysts, i.e. enzymes or translocators; (3) the molecular components of all traits in all cells are the products of systems of enzymes, i.e. of fluxing metabolic pathways; (4) any flux to the molecular components of a trait responds non-linearly (non-additively) to graded mutations in the activity of any one of the enzymes at a catalytic locus in a metabolic system; (5) as the flux responds to graded changes in the activity of an enzyme, the concentrations of the molecular components of a trait also change. CONCLUSIONS: It is then possible to account rationally, and without misrepresenting Mendel, for: the origin of dominant and recessive traits; the occurrence of Mendel's 3(dominant):1(recessive) trait ratio; deviations from this ratio; the absence of dominant and recessive traits in some circumstances, the occurrence of a blending of traits in others; the frequent occurrence of pleiotropy and epistasis.

Genes, Dominant↗
PubMed2003

Rational approaches to human cancer immunotherapy.

Over most of the 20th century, immunotherapy for cancer was based on empiricism. Interesting phenomena were observed in the areas of cancer, infectious diseases, or transplantation. Inferences were made and extrapolated into new approaches for the treatment of cancer. If tumors regressed, the treatment approaches could be refined further. However, until the appropriate tools and reagents were available, investigators were unable to understand the biology underlying these observations. In the early 1990s, the first human tumor T cell antigens were defined and dendritic cells were discovered to play a pivotal role in antigen presentation. The current era of cancer immunotherapy is one of translational research based on known biology and rationally designed interventions and has led to a rapid expansion of the field. The beginning of the 21st century brings the possibility of a new era of effective cancer immunotherapy, combining rational, immunological treatments with conventional therapies to improve the outcome for patients with cancer.

Animals↗
PubMed1975

The Dutch famine, 1944-1945, and the reproductive process. II. Interrelations of caloric rations and six indices at birth.

Effects of maternal exposure to famine during the prenatal period were compared among six indices of reproduction by the use of Z scores. Maternal weight was affected soonest, then birthweight and placental weight. Length and head size at birth were affected relatively less and only after exposure to more severe nutritional deprivation. Path models were constructed of the interrelations of caloric rations, length of gestation, maternal weight, and fetal dimensions. Above a threshold value of 1,5000 Cal dialy average official food rations available to mothers in the third trimester, a model in whichthe placenta is treated as a fetal dimension (or organ) seemed most appropriate. Below the threshold value, a model in which the placenta is treated as a transmitter of nutrients seemed most appropirate.

Birth Weight↗
PubMed1982

Corporate rationalization of American health care: a visitor's appraisal.

This paper uses elements of the macrotheory of advanced capitalist societies developed by Jurgen Habermas and other "critical theorists" to locate and explore the implications of the containing corporatization of the U.S. health care sector. It questions the often-dominant view that cost is the major problem of current U.S. arrangements, and shows how most recent government policies have reinforced the corporate rationalization of health care, or at least proved neutral towards it. Yet it can be argued that it is precisely this "rationalization" which renders more difficult both cost-control and the much-needed broadening of the agenda of the health care debate to important issues other than cost.

Cost Control↗
PubMed1978

Performance of the African giant rat (Cricetomys gambianus Waterhouse) on commercial rations and varying dietary protein levels.

The growth performance of 24 weanling giant rats was studied in 2 experiments of 30 weeks duration with commercial livestock rations and graded levels of protein. Daily average liveweight gain was 5.1-7.3 g, food consumption 26.9-36.3 g on 6 diets. Food intake, growth rate and food efficiency ratio were very similar using the different commercial diets. Growth performance improved as the dietary protein level was raised from 10 to 13%, but a further increase to 16% did not result in greater growth. The commercial pig ration and the experimental diet containing 13% dietary protein level were found to give satisfactory growth, and are recommended for studies with these animals.

Africa↗
PubMed1987

Rationalization and computerization of the drug supply to an animal unit.

Drug stocks in an animal unit were rationalized by discarding out-of-date or unwanted items and drawing up an approved stock list. A computerized system of stock control which enables a regular and accurate inventory of pharmaceuticals to be made was then established. In addition, the paperwork required for reordering drugs is produced automatically. Pharmaceuticals to a total value of 1650 pounds were discarded during the rationalization phase. The value of drugs stocked in the animal unit then stabilized at about one-third of previous levels. In the first 6 months of operation of the new system drug expenditure fell by about 40% in comparison with the same period 1 year previously. The drug stock control system has proved economical to operate and accurate, and can be run by persons without computer expertise. Valuable savings in both cost and labour have resulted. Effective management of drug expenditure by the animal unit is now possible.

Animals↗
PubMed2005

Tenth-order rational-harmonic frequency multiplication and detuning of optical pulse injection-locked erbium-doped fiber laser.

The jitter and frequency-detuning dynamics of a 10-GHz rational-harmonic frequency-multiplied pulse train generated from an erbium-doped fiber laser (EDFL) is studied. The EDFL is self-feedback seeded and optically injection locked by a gain-switched laser diode (GSLD) with a pulse width and an average power of 17.6 ps and 0.2 mW, respectively, at a repetition frequency of 1 GHz. The repetition frequency of the optical pulse train can be tenth-order multiplied by a slight detuning of the repetition frequency of the GSLD to match the rational-harmonic injection-locked condition of the EDFL. As the repetition frequency is multiplied from 1 to 10 GHz, the peak power, the pulse width, and the frequency-detuning bandwidth of the injection-locked EDFL pulses decrease from 1.2 to 0.3 W, from 40 to 21 ps, and from 40 to 9 kHz, respectively. The timing jitter of the injection-locked EDFL repeated at 1 GHz remains unchanged (< 0.5 ps) within the detuning bandwidth, which inevitably increases to 1.2 ps after tenth-order multiplication.

Journal Article↗
PubMed2005

End-of-life decision making is more than rational.

Most medical models of end-of-life decision making by patients assume a rational autonomous adult obtaining and deliberating over information to arrive at some conclusion. If the patient is deemed incapable of this, family members are often nominated as substitutes, with assumptions that the family are united and rational. These are problematic assumptions. We interviewed 23 outpatients with cancer about the decision not to resuscitate a patient following cardiopulmonary arrest and examined their accounts of decision making using discourse analytical techniques. Our analysis suggests that participants access two different interpretative repertoires regarding the construct of persons, invoking a 'modernist' repertoire to assert the appropriateness of someone, a patient or family, making a decision, and a 'romanticist' repertoire when identifying either a patient or family as ineligible to make the decision. In determining the appropriateness of an individual to make decisions, participants informally apply 'Sanity' and 'Stability' tests, assessing both an inherent ability to reason (modernist repertoire) and the presence of emotion (romanticist repertoire) which might impact on the decision making process. Failure to pass the tests respectively excludes or excuses individuals from decision making. The absence of the romanticist repertoire in dominant models of patient decision making has ethical implications for policy makers and medical practitioners dealing with dying patients and their families.

Australia↗