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An interdisciplinary approach to certain fundamental issues in the fields of physics and biology: towards a unified theory.

Recent experiments appear to have revealed the possibility of the existence of quantum entanglement between spatially separated human subjects. In addition, a similar condition might exist between basins containing human neurons adhering to printed circuit boards. In both instances, preliminary data indicates what appear to be non-local correlations between brain electrical activities in the case of the human subjects and also non-local correlations between neuronal basin electrical activities, implying entanglement at the macroscopic level. If the ongoing expanded research and the analysis of same continues to support this hypothesis, it may then make it possible to simultaneously address some of the fundamental problems facing us in both physics and biology through the adoption of an interdisciplinary empirical approach based on Bell's experimental philosophy, with the goal of unifying these two fields.

Animals↗

Prediction of the formation and stabilities of energetic salts and ionic liquids based on ab initio electronic structure calculations.

A computational approach to predict the thermodynamics for forming a variety of imidazolium-based salts and ionic liquids from typical starting materials is described. The gas-phase proton and methyl cation acidities of several protonating and methylating agents, as well as the proton and methyl cation affinities of many important methyl-, nitro-, and cyano-substituted imidazoles, have been calculated reliably by using the computationally feasible DFT (B3LYP) and MP2 (extrapolated to the complete basis set limit) methods. These accurately calculated proton and methyl cation affinities of neutrals and anions are used in conjunction with an empirical approach based on molecular volumes to estimate the lattice enthalpies and entropies of ionic liquids, organic solids, and organic liquids. These quantities were used to construct a thermodynamic cycle for salt formation to reliably predict the ability to synthesize a variety of salts including ones with potentially high energetic densities. An adjustment of the gas phase thermodynamic cycle to account for solid- and liquid-phase chemistries provides the best overall assessment of salt formation and stability. This has been applied to imidazoles (the cation to be formed) with alkyl, nitro, and cyano substituents. The proton and methyl cation donors studied were as follows: HCl, HBr, HI, (HO)2SO2, HSO3CF3 (TfOH), and HSO3(C6H4)CH3 (TsOH); CH3Cl, CH3Br, CH3I, (CH3O)2SO2, CH3SO3CF3 (TfOCH3), and CH3SO3(C6H4)CH3 (TsOCH3). As substitution of the cation with electron-withdrawing groups increases, the triflate reagents appear to be the best overall choice as protonating and methylating agents. Even stronger alkylating agents should be considered to enhance the chances of synthetic success. When using the enthalpies of reaction for the gas-phase reactants (eq 6) to form a salt, a cutoff value of -13 kcal mol(-1) or lower (more negative) should be used as the minimum value for predicting whether a salt can be synthesized.

Journal Article↗

Association therapy as a prognostic factor in deep fungal infection complicating oncohaematological diseases.

A group of 31 oncohaemopathic patients (17 male, mean age 44 +/- 6 years), diagnosed as having primary deep fungal infection involving the lungs, were retrospectively evaluated. When infection was suspected on a clinical basis the major associated risks for death were the duration of bone marrow aplasia (12 +/- 7 versus 21 +/- 6 days, P < 0.001), increase in white blood cells and, in particular, prolonged granulocytopenia (11 +/- 5 versus 24 +/- 8 days, P < 0.001) when survivors were compared with patients, who died. Our therapeutic empirical approach was based on the association of i.v. amphotericin B, 1 mg kg-1 day-1, with oral 5-fluorocytosine (5-FC) 150 mg kg-1 day-1. Only 9 subjects received combination therapy for more than 7 days. For majority of them, oral 5-FC was interrupted because of altered compliance or sustained liver damage. A chi 2 test for independent parameters showed (P = 0.0021) a concentration of deaths among patients who received amphotericin B alone (15/22); none of the patients treated with amphotericin B + 5-FC (9 cases) died. Results generally suggest that a more favourable outcome was statistically associated with empirical antifungal combination therapy in deep fungal infection, although both treatment regimens showed effectiveness in terms of survival. Nevertheless the low 5-FC compliance and the small sample do not indicate the safe use of this drug in a large population.

Adolescent↗

Population dynamics of nitrifying bacteria in an aquatic ecosystem.

In a space environment such as Space Shuttle or Space Station, animal experiments with aquatic species in a closed system pose a crucial problem in maintaining their water quality for a long term. In nature, ammonia as an animal wastes is converted by nitrifying bacteria to nitrite or nitrate compounds, which usually become nitrogen sources for plants. Thus an application of the biological reactor with such bacteria attached on some filters has been suggested and experimentally studied for efficient waste managements of ammonia. Although some successful results were reported (Kozu et al. 1995, Nagaoka et al. 1998, Nakamura et al. 1997, 1998) in the space applications, purely empirical approaches have so far been taken to develop a biological filter having a stable nitrifying activity. In this study, we constructed a mathematical model to deal with the dynamics of the ammonia nitrifying processes in a biological reactor. The model describes population dynamics of the ammonia-oxidizing bacteria and the nitrite-oxidizing bacteria cultivated on the same filter. We estimated parameters involved in the model using the experimental data. The result shows that these estimated parameters could be applied to general cases and that the two bacteria are in a symbiotic relationship; they can better perform when both coexist, as has been empirically recognized. Based on the model analysis, we discuss how to prepare a high performance biological filter.

Ammonia↗

The allometric approach for interspecies scaling of pharmacokinetics and toxicity of anti-cancer drugs.

1. The rationale for extrapolation or 'scaling' across animal species is based on their underlying anatomical, physiological and biochemical similarities. 2. Research carried out in the 19th and early 20th century resulted in Benedict's famous 'mouse-to-elephant' graph which showed that the log of the basal metabolic rate plotted against the log of bodyweight (W) produced a straight line with a slope of 0.76. Since then it has become apparent that a number of other physiological variables (Y) exhibit a similar relationship which can be represented by the general allometric equation, Y = alpha W beta; where beta is the slope of the log-log plot and alpha is the intercept on the y axis. 3. The major pharmacokinetic parameters such as clearance and volume of distribution of many drugs are also related to W in a similar manner. 4. This empirical approach does not require a strong mathematical background and offers a relatively simple method of predicting the kinetics of anti-cancer drugs in patients from pre-clinical animal data. 5. The occurrence of major qualitative and quantitative differences in the metabolism of drugs between species is probably the single greatest complicating factor in the use of animals as predictors of drug toxicity and kinetics in patients. 6. Despite this, the allometric approach is useful for allowing the estimation of a more appropriate starting dose for some drugs in a Phase I trial, which might result in potential savings in escalation steps and maximize the chance that the dose which an individual receives has the potential for therapeutic value.

Animals↗

Predicting the consequences of social stressors on pig food intake and performance.

The influence of social stressors on pig performance, although undeniable, is frequently underestimated, and in pig growth modeling is generally ignored. The aims here were to quantify the effects of the main social stressors (i.e., group size, space allowance, feeder space allowance, and mixing) on the performance of growing pigs and to incorporate these relationships into a general growth simulation model. Effects of the individual stressors were described by conceptual equations derived on biological grounds. Parameter values were estimated from experimental data, while taking steps to avoid the problems of using a strictly empirical approach. It was assumed that social stress decreases the capacity of the animal to attain its potential. This is equivalent to lowering the maximum rate of daily gain (ADGp, kg/d). Because it is generally assumed that animals eat to attain their potential, a decrease in ADGp necessarily leads to a decrease in intake. Genetic variation among genotypes in their ability to cope with social stressors was accounted for by introducing an extra genetic parameter (EX) into the model. The value of EX adjusts both the intensity of stressor at which the animal becomes effectively stressed and the extent to which stress decreases performance and increases energy expenditure at a given stressor intensity. Rather than using an empirical adjustment to predict values for the model output variables, such as intake and gain, the chosen functional forms were integrated into a general growth model as mechanistic equations. This allowed the effects of interactions that exist between social stressors and the other variables, such as the genotype, feed composition, and environment on pig intake and growth, to be explored and, at least in principle, predicted. The adapted model is able to predict the performance of pigs differing in both the potential and ability to cope with environmental stressors when raised under given dietary, physical, and social environmental conditions. The social stressor equations developed here can be incorporated into other pig growth simulation models.

Animal Feed↗

Determination of solubility parameters for poly(3-hydroxyalkanoates).

The three dimensional solubility parameters defined by Hansen are based on dispersion forces between structural units, interaction between polar groups and hydrogen bonding. For polar polymers such as poly(3-hydroxyalkanoates), P(3HA), this approach was used to obtain the three coordinates of a solubility parameter in terms of: a dispersion part, a polar part and a hydrogen bonding part. Thirty-eight different solvents for poly(3-hydroxybutyrate), PHB, which are mentioned in the literature are examined by this method and the theoretical predictions are compared with the experimental reports. Another overall comparison between PHA polymers provides their Hansen and Hildebrand parameters for side chain lengths up to C13. In this series a linear progression in calculated solubility parameters with side chain length was found. An Appendix provides information and data on calculation of the solubility parameters. While the solubility information is limited and only covers homopolymers, it should help to highlight some of the contradictions regarding PHB solubility. This semi-empirical approach is only valid for amorphous polymers hence crystallinity effects, which are important with PHB, as well as molecular weight effects still require analysis.

Hydrogen Bonding↗

Herbaceous covers to control tree invasion in rights-of-way: ecological concepts and applications.

In northeastern America, thousands of kilometers of utility rights-of-way (ROWs) have to be managed to prevent the establishment of a tall vegetation cover that does not comply with safety and maintenance regulations. Recent decades have seen the emergence of ecologically based vegetation control strategies to reduce environmental impacts as well as maintenance costs. One such strategy is to take advantage of competitive herbaceous covers to limit tree invasion. This approach, however, as well as its fundamental underlying principles, has been little scrutinized. In this article, (1) we present the main ecological concepts supporting the use of a herbaceous cover to limit tree invasion, emphasizing naturally forested ecosystems of northeastern America. They include reported evidence of stable plant communities and an overview of potential underlying mechanisms of inhibition. (2) We then review field applications, specifically testing the ability of seeded herbaceous covers to control tree invasion in ROWs. (3) We discuss unresolved issues relevant to management and research. The available evidence suggests that seeding herbaceous covers in ROWs can help control tree invasion, but many issues still limit broad-scale applications. The various interactions that govern plant community dynamics are far from being fully understood, so selecting species still largely depends on an empirical approach. Patterns of resistance to tree invasion must be investigated over a wide range of spatial, historical, and environmental contexts to determine effective management and seeding practices that will lead to broad-scale applications. We suggest establishing communities rather than single dominant species and using as much as possible native species to limit risks of invasion.

Ecology↗

Diagnostic testing to establish a microbial cause is helpful in the management of community-acquired pneumonia.

Antibiotic treatment for community-acquired pneumonia (CAP) can be specifically directed at an identified etiologic agent, or empirically formulated based on consideration of the likely pathogens according to the patient's age, underlying diseases, and clinical presentation. In recent years the empirical approach has become increasingly popular, and there is a growing trend away from efforts to make a microbiological diagnosis. This article reviews the tests that are currently available for the diagnosis of CAP, including stains, cultures, antigen-detection techniques, nucleic acid amplification, and serologies. Arguments then are presented in support of efforts to make a microbiological diagnosis. Clinical and radiographic features of CAP are not sufficiently distinctive to infer a specific microbial cause. Identification of the etiologic agent can be made in the majority of cases, and most microbiological diagnoses can be made rapidly with simple tests. The best opportunity to make an etiologic diagnosis is before antibiotics are administered. Identification of the microbial cause of pneumonia permits specific, narrow-spectrum antibiotic treatment that may be more effective, less toxic, and less expensive than empiric therapy. Microbiological data from individual patients contributes to understanding the local microbial epidemiology of CAP, including the local distribution of pathogens and their antimicrobial resistance patterns, information that is invaluable in the construction and modification of empiric treatment regimens. The reliance on empiric treatment engenders a false complacency, based on the erroneous assumption that broad-spectrum antibiotics will treat all cases of CAP. The unnecessary use of broad-spectrum antibiotic combinations in the empiric treatment of CAP contributes to the growing problem of antimicrobial resistance.

Anti-Bacterial Agents↗

An empirical method to refine personality disorder classification using stepwise logistic regression modeling to develop diagnostic criteria and thresholds.

This study of DSM-III-R personality disorder (PD) classification provides an empirical approach to determine (1) the discriminative power of each criterion and (2) the optimal number of criteria needed to diagnose the presence of each PD. A semistructured assessment of 110 outpatients was performed for the 11 PDs and their 104 diagnostic criteria. Sensitivity, specificity, and predictive powers were calculated for each criterion item. Logistic regression was performed to determine (1) univariate weightings of the individual criteria as applied to a given diagnosis, and (2) multivariate measures of the criteria that significantly improved the chi-square value in a stepwise fashion. The significant items were then equally weighted to calculate the optimal number needed to diagnose category membership. Of 104 PD criteria, 41 discriminated at a significance level of .05 or less, and each PD could be optimally diagnosed with fewer criteria than currently required. We can empirically reduce the number of criteria combinations comprising individual categories, decrease heterogeneity, and narrow diagnostic boundaries. This increases the likelihood of identifying etiological factors, predictors of clinical course, specific treatments, familial aggregation, and neurobiological correlates for the PD taxa.

Adolescent↗

Empirical treatment with fibrinolysis and early surgery reduces the duration of hospitalization in pleural sepsis.

The efficacy of three different treatment protocols was compared: 1) simple chest tube drainage (Drain); 2) adjunctive intrapleural streptokinase (IP-SK); and 3) an aggressive empirical approach incorporating SK and early surgical drainage (SK+early OP) in patients with pleural empyema and high-risk parapneumonic effusions. This was a nonrandomized, prospective, controlled time series study of 82 consecutive patients with community-acquired empyema (n=68) and high-risk parapneumonic effusions (n=14). The following three treatment protocols were administered in sequence over 6 years: 1) Drain (n=29, chest catheter drainage); 2) IP-SK (n=23, adjunctive intrapleural fibrinolysis with 250,000 U x day(-1) SK); and 3) SK+early OP (n=30, early surgical drainage was offered to patients who failed to respond promptly following initial drainage plus SK). The average duration of hospital stay in the SK+early OP group was significantly shorter than in the Drain and IP-SK groups. The mortality rate was also significantly lower in the SK+early OP than the Drain groups (3 versus 24%). It was concluded that an empirical treatment strategy which combines adjunctive intrapleural fibrinolysis with early surgical intervention results in shorter hospital stays and may reduce mortality in patients with pleural sepsis.

Adolescent↗

Redefining disease? The nosologic implications of molecular genetic knowledge.

How will developments in genetic knowledge affect the classification of disease? Leaders in genetics have suggested that knowledge of the role of genes in disease can determine nosology. Diseases might be defined by genotype, thus avoiding the limitations of more empirical approaches to categorization. Other commentators caution against disease definitions that are detached from the look and feel of disease, and argue for an interplay between genotypic and phenotypic information. Still others attribute nosologic change to social processes. We draw on an analysis of the scientific literature, our conversations with genetics clinicians, and reviews of patient organization Web sites to offer a revised interpretation of the nosologic implications of molecular genetic knowledge. We review the recent histories of three diseases--hemophilia, Rett syndrome, and cystic fibrosis--to argue that nosologic change cannot be explained by either biologic theories of disease etiology or sociologic theories of social tendencies. Although new genetic information challenges disease classifications and is highly influential in their redesign, genetic information can be used in diverse ways to reconstruct disease categories and is not the only influence in these revisions. Ironically, genetic information is likely to play a central role in producing a new, but still empirical, classification scheme.

Cystic Fibrosis↗

Inhibition of return: a graphical meta-analysis of its time course and an empirical test of its temporal and spatial properties.

Immediately after a stimulus appears in the visual field, there is often a short period of facilitated processing of stimuli at or near this location. This period is followed by one in which processing is impaired, rather than facilitated. This impairment has been termed inhibition of return (IOR). In the present study, the time course of this phenomenon was examined in two ways. (1) A graphical meta-analysis plotted the size of the effect as a function of the stimulus onset asynchrony (SOA) of the two stimuli. This analysis showed that IOR is impressively stable for SOAs of 300-1,600 msec. It also showed that the literature does not provide any clear sense of the duration of IOR. (2) An empirical approach was, therefore, taken to fill this gap in our knowledge of IOR. In three experiments, IOR was tested using SOAs between 600 and 4,200 msec. IOR was robust for approximately 3 sec and appeared to taper off after this point; the observed duration varied somewhat as a function of the testing conditions. In addition, for the first second, the degree of inhibition was inversely related to distance of the target from the original stimulus, but for the next 2 sec this spatial distribution was not observed. Theories of the mechanisms and function of IOR must conform to these spatial and temporal properties.

Attention↗

Paradigm shifts: new techniques to answer new questions.

The advent of a multiple-channels approach to spatial vision 20 years ago raised important questions that were difficult to approach empirically, given the technology and analytic tools of the time. These questions concerned the interaction or combination of different components of a stimulus--questions that have recently resurfaced in more complex form. Classical psychophysical methods for assessing whether two stimulus aspects are coded independently (e.g., masking, adaptation, and cue-summation) provide only limited information about the nature of whatever interactions are discovered. In both older work in detection and recent work in complex pattern discrimination, we have used a double-judgment paradigm in which the observer rates two aspects of a stimulus simultaneously. The paradigm provides a rich source of information about the codes underlying each psychophysical decision and which are unique in permitting us to psychophysically investigate effects resulting from neural noise in the system. Our analyses draw on theories of dimensional interaction in signal detection theory and in information theory, and on methods from several branches of statistics, including categorical data analysis and structural equation modeling. We review the theoretical, technological, methodological, and personal influences that led us to develop this approach.

History, 20th Century↗

Spiritual issues associated with traumatic-onset disability.

PURPOSE: The present study used a qualitative approach to discover the concepts used by people with a sudden-onset disability to express issues of spirituality. Using a cross-sectional time frame, the study sought to understand how spiritual issues were experienced at the onset of a disability from the perspective of the disabled person him or herself. The study also compared the perceptions of brain injury respondents to spinal cord injury respondents. METHOD: The qualitative approach was chosen to capture a detailed understanding of perceptions about spirituality, and the relationship of the disability to the disabled person's spiritual beliefs. The sample consisted of 16 individuals, all of whom had experienced a spinal cord injury or a brain injury. RESULTS: The main findings of the study were as follows: (1) Participants recovering from a disability described spiritual issues relating to five themes which arose directly from the data (awareness, closeness, trust, purpose, vulnerability) and relating to three relationships found throughout the literature on spirituality (intrapersonal, interpersonal and transpersonal). These eight dimensions can be combined to form a matrix, which serves as a framework for considering spiritual issues associated with disability; and (2) There were differences in the spiritual concepts described by the participants with brain injury compared to those with spinal cord injury. In particular, those with brain injuries seemed to place greater emphasis on the importance of their families, and to be more aware of the need for trust in view of their memory deficits. CONCLUSIONS: These results represent one of the earliest attempts to take an empirical approach to the development of theory in the area of spirituality and disability. Building on theory developed in other populations (palliative care and ageing), the study offers a theoretical model for clinicians, educators and researchers to better understand spirituality in the context of disability.

Acute Disease↗

Psychiatric issues in retrospective challenges of testamentary capacity.

BACKGROUND: Challenges to Wills on the basis of lack of testamentary capacity are likely to increase due to a combination of economic factors, high prevalence of mental disorders in old age and the complexity of many modern families. Geriatric psychiatrists and other experts will be asked to provide expert assessment of the testamentary capacity of individuals whose Wills are being challenged retrospectively. The traditional criteria described in the Banks vs Goodfellow case have been held as the standard for testamentary capacity. However, these criteria may not be comprehensive enough for the coming generation of expert assessors. METHOD: The literature and selected international case law relevant to testamentary capacity were reviewed. Particular focus is placed on the conceptual and empirical approaches to the assessment of complex capacities that may inform the development of specific legal standards. In addition, 25 consecutive medico-legal reports on retrospective testamentary capacity were analyzed according to co-morbid medical and psychiatric disorders as well as psychosocial and behavioural variables. Illustrative case vignettes are included. RESULTS: The typical profile for retrospective challenges to testamentary capacity included a radical change from a previous Will (72%), where undue influence was alleged (56%), in a testator with no biological children (52%), who executed the Will less than a year prior to death (48%). Co-morbid conditions were dementia (40%), alcohol abuse (28%) and other neurological/psychiatric conditions (28%). CONCLUSIONS: While Banks vs Goodfellow continues to provide a sound basis for assessing testamentary (task-specific) capacity, the complexity and subtlety of the issues reflected in these cases highlight the need to go beyond the traditional criteria and assess situation-specific factors. Expert assessors need to determine whether the testator appreciated the consequences of executing or changing a Will, especially when there has been a radical change in the context of a complex or conflictual family environment. Empirical studies addressing the cognitive functions relevant to testamentary capacity and the development of legal standards based on a competency construct may also help to inform retrospective capacity assessments.

Aged↗

Neurologic disease described in the Journal of Empirical Psychology (Gnothi Sauton oder Magazin zur Erfahrungsseelenkunde), 1783-1793.

Know Thyself or Journal of Empirical Psychology (Gnothi Sauton oder Magazin zur Erfahrungsseelenkunde), 1783-1793, was the first of its kind--concentrating on nervous and mental disturbances and marking the beginning of periodical neuropsychiatric publications. The editor, Karl Philipp Moritz, and the contributors, many of them lay people, were particularly interested in disturbances of language and consciousness. Descriptions of epilepsy, Sydenham's chorea, jargon aphasia, and dementia are briefly summarized. The case material from the Journal was soon translated and integrated in later work. The Journal itself and its "empirical" approach became a model for publications that followed.

History, 18th Century↗

How Twin Cities neurologists treat ischemic stroke. Policies and trends.

OBJECTIVE: To examine community practices. DESIGN: Physician practice policies were surveyed using case vignettes in which evaluation for carotid endarterectomy or use of anticoagulation therapy was at issue. Virtually the same group was surveyed in 1988 and again in 1991, after publication of carotid endarterectomy trials in symptomatic patients. SETTING: Greater Metropolitan Minneapolis-St. Paul, Minnesota. PARTICIPANTS: Community and academic neurologists in practice of general adult neurology. MEASUREMENT: Percentage of respondents who would recommend the management option in question for each vignette. RESULTS: Ninety-eight percent favored evaluation for carotid endarterectomy in appropriately symptomatic "good risk" patients in 1988 before proof of efficacy became available. Proof increased the percentage (from 67% to 92%) favoring evaluation in older, sicker, symptomatic patients but not the percentage of those favoring evaluation of bruit patients (1988: 33%; 1991: 24%). In 1991, a lower percentage recommended warfarin therapy after noncardioembolic transient ischemic attack; this was especially apparent in the vertebrobasilar case (1988: 59%; 1991: 37%). Both years, nine of 10 neurologists recommended heparin therapy for progressing stroke, while half to three-fourths used it after partial stroke or transient ischemic attack. Almost all would use anticoagulants for secondary prophylaxis after suspected cardioembolic stroke. CONCLUSION: The results reflect a treatment-oriented empirical approach in this community and document quick clinical application of scientific evidence when it became available.

Aged↗