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[Neuroscience at the end of the 2nd millennium: a shift in paradigms].

The new neuroscience data rapidly accumulating by the end of the second millennium calls for radical revision of many long-established and widely accepted postulates. This paper reviews some data leading to new concepts of life and work of neurons. The adult brain contains stem cells which are the source of the precursors for all main types of the brain cells: neurons, astrocytes, and oligodendroglia. These cells can substitute the deteriorating elements in the adult and even old brain. The neurons occur to be highly resistant to lesion of their processes as well to anoxia, and inhibitory neurons are shown to be especially stable in some pathological conditions. Changes in the afferent inputs result in various types of rapid compensatory morphological and functional reorganizations at different levels. Thus, the previous fatalistic view of the nervous system is substituted now for an optimistic one regarding various possibilities of prolongation and restoration of normal functioning of the brain. Simultaneously, our concepts of the neurons changed drastically. An unitary neuron may operate by several neurotransmitting substances; their synaptic influences upon the dendrites may evoke the active propagation of calcium and sodium spikes, their axons may differentially release transmitter substances depending on parameters of excitation. All neuronal functions are helped and controlled by astroglia, which participates in the synthesis of transmitters and protects the neurons from the excitotoxic death. Besides the synaptic interactions between the neurons, there exist other types of communications, such as volume conduction of transmitters after their spillover from the excited synapses and non-synaptic (varicose) zones, as well as exchange of molecules and ions through the gap junctions. A complex picture of interneuronal communications with multiple synaptic, presynaptic, and parasynaptic interactions is further complicated by the intimate participation of neurotrophic substances and "mediators of the immune system"--cytokines in these processes. The mutual regulatory influences between neurotransmitters, neurotrophic, and neuroimmune systems show that in normal conditions all they are working in concert. This increase in number of factors determining the final result of interaction between the neurons contributes new difficulties to the development of theoretical concepts or simulation of brain functions. In this context it is possible to speak about a certain crisis of theoretical neurobiology at present, because multiplicity of fine details obtained by molecular neurobiology and neurogenetics cannot be integrated in a coherent view of the brain functions. Overcoming the present gap between the analytic and synthetic approaches to understanding the brain work will be the main aim for the neurobiologists of the third millennium.

Animals↗

Decision support: a paradigm addition for patient safety.

The creation of a decision culture that matches the "decision intensity" of the healthcare field is not a paradigm shift but rather a paradigm addition that properly addresses all aspects of information, from how it is delivered to how it is managed. These changes will take healthcare beyond its current emphasis on efficient transaction systems to reach safe and effective clinical decision environments, which cannot be achieved with transaction mentalities and processes.

Clinical Pharmacy Information Systems↗

[Laparoscopic surgery. A shift in paradigm?].

Since it was first introduced at the beginning of the century, laparoscopy has been developed by pioneers in the field of gynaecological surgery from a diagnostic aid to a high tech tool for use in various branches of surgery. In the near future, this rapidly developing technique, with three-dimensional video and robot-assisted surgery, will require well planned theoretical and practical training.

Abdominal Injuries↗

TNM staging of cancers of the head and neck: striving for uniformity among diversity.

The sixth edition of the tumor-node-metastasis staging system for head and neck cancers incorporates some significant shifts in philosophy. As treatment paradigms shift and data from ongoing clinical and basic research become available, further revisions may be expected in the future. The purpose of this review is to highlight the complexities involved in developing a user-friendly staging system and to report the major changes in the new version. The authors also discuss some areas of current interest that may have the potential to lead to future modifications.

Head and Neck Neoplasms↗

Obstetrics and gynecology at the crossroads--again? Still!

It seems, if one can believe presidential addresses, as if our specialty is always at some crossroads or other. In this "opinion piece," uniquely, I don't complain about managed care. I do attempt to identify some of the issues that will be of import for obstetrics and gynecology in the near and not-so-near futures. With regard to research, we await breakthroughs, for example, in the early detection of ovarian cancer, so as to finally be able to improve outcomes. A problem, though, is our failure to focus enough effort on developing a cadre of clinician scientists, who can work out research findings with direct clinical application; this is an issue with which the specialty needs to come to grips. Regarding education, I believe we need to refocus from what type of practitioners we might want to produce to best meet the needs of our patients. The bottom line should be more flexibility in training and emphasis on clinical competence, so that excellent practitioners with competence across the breadth of our specialty are available to provide a full range of appropriate women's health care. The concept of "women's health" is controversial and evolving rapidly. Review of several available sources suggests that reproductive medicine will remain an important component of women's health but that our specialty must now evolve to include other areas, as the major health problems of women change. We need to shift from an organ-based paradigm to a more holistic view, reflecting the woman-centered focus for our specialty. This "paradigm shift" will need to entail continuation of first-rate surgical and obstetrics services but will be expanded to include a full range of services, probably offered by highly trained and competent individuals with specific areas of expertise, practicing in a multi-single-specialty group. Obstetrics and gynecology at the crossroads, indeed!

Humans↗

Quantitative assessment of the fingerprint evidential value using machine learning.

Fingerprints as physical evidence have long supported criminal investigation and adjudication. In practice, however, fingerprint identification relies mainly on examiners' experience. Furthermore, expert opinions tend to be categorical, even though the opinions with the same conclusion could differ substantially in evidential strength. To quantitatively assess fingerprint evidential value, this study proposes a machine learning-based framework as an interpretable decision-support tool. A lightweight residual one-dimensional convolutional neural network was constructed, incorporating channel recalibration and a similarity-driven attention mechanism to learn adaptive contribution weights for different matched minutiae (minutiae for short). Controlled experiments revealed that the predicted evidential value increased with the number of minutiae and was significantly influenced by the quality of minutiae. With 10 minutiae, the mean predicted scores were 4.49, 7.00, and 9.09 for blurred, moderately blurred, and clear minutiae, respectively. Multiple regression analysis indicated that replacing a pair of blurred minutiae with a pair of clear minutiae increased the score by 0.492, whereas replacing it with a pair of moderately blurred minutiae increased the score by only 0.216. By mapping predicted scores to graded levels of evidential strength, the framework contributes to a paradigm shift from categorical expert opinions to graded ones, helping courts evaluate fingerprint evidence more scientifically.

Humans↗

Reaction time paradigms in subjects at risk for schizophrenia.

Deviant response patterns in experimental reaction time paradigms in schizophrenic probands are well documented. Although simple reaction times are strongly influenced by the current psychopathological status of the proband (e.g. florid psychotic patients versus remitted patients) these influences are less clear for measures obtained from more complex reaction time paradigms. These include the crossover paradigm (reaction time to stimuli presented after constant preparatory intervals in comparison to reaction time to stimuli presented after irregular preparatory intervals) and the modality shift paradigm (reaction time to a stimulus (light or tone) when the modality of the stimulus on the preceding trial was the same compared to when it was different). It is not clear if these peculiarities of response patterns occur as a consequence of the disease or if they represent vulnerability markers for schizophrenia. Both crossover reaction time and modality shift reaction time paradigms were applied to 56 drug free schizophrenics, 45 healthy siblings of these patients and 68 healthy controls. The results indicate that retarded reaction times and the occurrence of the crossover effect as well as of the modality shift effect distinguish schizophrenics and controls. Healthy siblings of schizophrenics differed from healthy controls with regard to the crossover effect but not with regard to the modality shift effect. Therefore only the crossover effect represents a vulnerability marker for schizophrenia. Correlations between the modality shift and the crossover effect revealed strong correlations in the schizophrenic group only.

Adolescent↗

Lived fictions: moving from pharmacology to ethnography.

While positivist science dominates the drug and alcohol research sector, alternative constructivist paradigms of inquiry into drug and alcohol use are also present. The passage of individual researchers through paradigm shifts is often difficult, and rarely documented. Different paradigms of inquiry produce different types of information. The use of the psychoactive drug methylenedioxymethamphetamine (MDMA or "Ecstasy") is discussed in light of a multidisciplinary investigation into the pharmacology and use of MDMA. The role of the author in interpreting data from both positivist and constructivist paradigms is highlighted by documenting a researchers' changes in epistemology whilst undertaking multidisciplinary research. It is concluded that multidisciplinary research into drug and alcohol use could benefit from evaluation of the processes that frame how information from both research paradigms is interpreted and integrated.

Journal Article↗

Recent developments and future issues in the use of health status assessment measures in clinical settings.

This paper provides a broad overview of the assessment of health status in clinical practice in three parts. Yesterday: The nation has undergone a paradigm shift in health-related thinking. The former paradigm emphasized only disease; the new emphasizes health, functioning, well-being, and disease. Measures of health and disease have evolved to reflect the new paradigm. Many are designed for clinical settings, based on measurement science, and are relatively brief. These newer measures have been used to document the natural history of disease, evaluate treatment effectiveness, and improve clinical case management. Today: Two barriers block full-scale use in clinical settings. The first barrier involves the meaning and interpretation of health status scores. Patients' scores are influenced by several types of patient mix variables and the timing of measurements. Interpretation is enhanced by valid normative data displaying the variability in health status among homogenous patient groups. The second barrier is utilization and mainstreaming. It involves all of the issues associated with changing the day-to-day behavior of clinicians and providers' routine processes to facilitate routine use of health status measures in clinical settings. Tomorrow: In the next decade, the nation will attempt to overhaul the health care system. As it does so, it will struggle with many issues: 1) clarifying the true aim of health care; 2) standardizing measures of health across patients, providers, and settings to evaluate benefit; 3) establishing cause and effect among structural-input factors, care delivery processes, and health outcomes valued by society; and 4) determining if and when cost containment actions have adverse effects on health outcomes. In this context, the importance of interpreting change in health status has a central role.

Activities of Daily Living↗

L-dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction.

A group of ten patients with idiopathic Parkinson's disease (PD) was tested on a series of automated tests of learning, memory, planning and attention whilst either on or off L-dopa medication. Controlled withdrawal of L-dopa interfered with aspects of performance on three of the tests that had previously been shown to be sensitive to frontal lobe dysfunction; a spatial working memory task, the Tower of London planning test, and a visual discrimination paradigm that also included intra- and extra-dimensional shift tests of selective attention. More specifically, errors were increased in the spatial working memory test, and both the accuracy and latency of thinking were impaired. Thinking time was significantly slowed following L-dopa withdrawal, even though the possible contaminating effects on motor slowing were fully controlled by a yoked control procedure. Nine out of ten patients reached a further stage of the visual discrimination, set-shifting paradigm when on, rather than off, L-dopa medication. Spatial span was also impaired off medication, but there were no effects of L-dopa withdrawal on tests of pattern and spatial recognition memory, simultaneous and delayed matching to sample or visuospatial conditional associative learning. Comparisons with a large control group confirmed previous findings that PD is associated with deficits on the majority of these tests. The results are discussed in terms of the fronto-striatal, dopamine dependent nature of some of the cognitive deficits found in PD, but the apparent dopamine-independent nature of deficits in other aspects of cognitive functioning, notably in tests of visual recognition memory and associative learning.

Brain Diseases↗

Rehabilitation of endogenous task shift processes in closed head injury patients.

This paper reports a study that was aimed to rehabilitate executive functions in CHI patients. When a subject is engaged in two speeded tasks, not simultaneously but with some form of alternation, the response is slower to an item of task A if it was preceded by an item of task B, than when it was preceded by an item of task A. This shift cost is small when subjects can prepare in advance for the new task (endogenous task shift), whereas the cost is much greater when preparation is not possible (exogenous task shift). The groups tested comprised 20 severe closed head injury (CHI) patients (10 who underwent treatment and 10 controls), 8 mild CHI patients, and 18 non-brain damaged (NBD) controls. In the present study, the shift cost was greater for severe CHI patients than for NBD controls. Treatment consisted of five sessions, in which an endogenous task shift paradigm was used. A significant reduction of the endogenous shift cost from assessment to retest was found. The reduction remained stable at the 4-month follow-up session. These results are not simply due to retesting, as the control patients did not show any improvement at retest. Interestingly, no reduction of exogenous task shift cost was found. The results showed also that the beneficial effect of the treatment generalises to other executive functions.

Adolescent↗

Neonatal exposure to cocaine enhances the reward-potentiating properties of the drug in young adult animals.

Either cocaine (20 mg/kg) or saline vehicle was administered to rat pups once daily on postnatal days 1-8. The enhancement of brain stimulation reward (BSR) by acute administration of cocaine (2.5, 5, and 10 mg/kg i.p.) was assessed in adult offspring (70-90 days of age) using a rate-frequency curve-shift paradigm. Acute administration of cocaine produced orderly dose-related shifts of the rate-frequency function toward lower frequencies in all groups indicating a reward-enhancing effect of the drug on BSR. However, offspring neonatally exposed to cocaine displayed a greater drug-induced potentiation of BSR. Of particular note, the small but significant enhancement of the reward-potentiating properties of cocaine was more pronounced in female offspring neonatally exposed to the drug. These findings indicate that the rewarding properties of cocaine were altered by neonatal exposure to the drug in a sexually dimorphic fashion.

Age Factors↗

Continuity and discontinuity in the historical development of modern psychopharmacology.

In the middle of the twentieth century psychiatry underwent a transition that is often referred to as the "psychopharmacology revolution." Implicit in the term revolution is the idea that a paradigm shift occurred. Specifically, it has been argued that psychiatry abandoned the psychoanalytic paradigm in favor of a qualitatively distinct conceptual system based on brain chemistry. The validity of this view requires that psychoanalysis had the status of a paradigm. This paper presents evidence that psychoanalysis did not constitute a paradigm and that the advent of psychopharmacology was not, technically, a scientific revolution. Instead, the rise of modern psychopharmacology was the culmination of a linear growth of biological knowledge that began to develop in the nineteenth century.

History, 20th Century↗