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PubMed2006

Human hormone function emulator.

This paper describes the addition of simulated hormone action to the author's modular, open-systems, computerized human nervous system function emulator. For this project he revived his 32-year old design for a pulse-integrating artificial neuron with controlled voltage droop and reset, to serve as the principal linear computational element. This neuron sums bursts of quantized presynaptic impulses to produce a simulated altered cell membrane voltage. When coupled with a variable-threshold Schmitt trigger, voltage changes can initiate a mock action potential signal. These altered neural membrane voltages and action potential signals are utilized in the nervous system emulator to qualitatively emulate the level of simulated hormone activity, to react to changes in the electrochemical environment, and to signal initiation of high level behavioral responses in the artificial intelligence system.

Action Potentials↗
PubMed1999

Space radiation concerns for manned exploration.

Spaceflight exposes astronaut crews to natural ionizing radiation. To date, exposures in manned spaceflight have been well below the career limits recommended to NASA by the National Council of Radiation Protection and Measurements (NCRP). This will not be the case for long-duration exploratory class missions. Additionally. International Space Station (ISS) crews will receive higher doses than earlier flight crews. Uncertainties in our understanding of long-term bioeffects, as well as updated analyses of the Hiroshima. Nagasaki and Chernobyl tumorigenesis data, have prompted the NCRP to recommend further reductions by 30-50% for career dose limit guidelines. Intelligent spacecraft design and material selection can provide a shielding strategy capable of maintaining crew exposures within recommended guidelines. Current studies on newer radioprotectant compounds may find combinations of agents which further diminish the risk of radiation-induced bioeffects to the crew.

Aerospace Medicine↗
PubMed2000

Medico-legal issues surrounding medical countermeasures used in the Gulf War--part 1.

When the multinational force deployed to the Gulf after Iraq's invasion of Kuwait in 1990, military intelligence assessed the Iraqi's as possessing and being capable of using weapons of mass destruction. There was judged to be a real threat that chemical weapons, especially nerve agents, and certain biological weapons would be used. Coalition countries attempted to reduce the effects by the use of medical countermeasures. Since the Gulf conflict a series of medico legal problems from this policy have arisen; some of which have formed the basis of claims against MOD. In this paper I shall review how consent to treatment may have been modified in the military operational context and by the interface with military law. I shall look at the issues of clinical negligence and how duty of care may be affected. In the next article I shall look at relevant employment law; briefly review how medicines regulatory provision applies to medical countermeasures, whether they were properly licensed and whether in any case this applied to the Ministry of Defence in the context of deployment to the Gulf War.

Humans↗
PubMed2001

Current laboratory methods for biological threat agent identification.

The authors present an integrated approach for the identification of biological threat agents. The methods used have been used extensively in field exercises and during response to incidents of biological terrorism. A diagnostic system, which integrates the clinical diagnosis or medical intelligence with immunodiagnostic tests, rapid gene amplification assays, and standard culture, provides results of the highest quality and confidence. In the future, selected reagents and technologies will be distributed through a network of civilian and military laboratories.

Bacterial Infections↗
PubMed2001

[General features of biological war].

After a historical introduction, the author points out the situation on the Biological and Toxin Weapons Convention of 1972, the biological programmes and the power's attitudes. Biological agents characteristics are quoted, as well as the difficulties to convert them into weapons and its massive bioterrorist use. Likely agents are listed and protection techniques, or epidemiological fight, are explained according to the classical 3-link acting method: sources, environment, and susceptible. The author emphasizes the importance of intelligence and cooperation between military health and civil protection services.

Biological Warfare↗
PubMed1980

The family-oriented home visiting program: a longitudinal study.

Designed and tested a home-based intervention program for low-income mothers with toddler and at least one other child under five. Sex of toddlers and race (black or white) about equally divided. Nine months of weekly home visits were specifically planned for each mother to enhance her effectiveness as an educational change agent. Treatment was planned to promote skills and understandings applicable over range of ages. Pretests, immediate posttests, and posttests one and two years later were administered to 27 experimental families and to a randomly assigned control group of 20. At .05 level of significance or beyond, experimentals excelled controls on receptive language test (toddler), on the Caldwell HOME (mother was indirectly rated as an educational change agent), and on a measure of teaching style (mother). They were also significantly superior on the Binet (toddler) at second posttest. No differences found with older siblings on Slosson Intelligence Test. Differences at third posttest were at least as great as earlier ones on mother measures. Relationships among child and mother measures are discussed.

Child Behavior Disorders↗
PubMed2005

IQ and blood lead from 2 to 7 years of age: are the effects in older children the residual of high blood lead concentrations in 2-year-olds?

Increases in peak blood lead concentrations, which occur at 18-30 months of age in the United States, are thought to result in lower IQ scores at 4-6 years of age, when IQ becomes stable and measurable. Data from a prospective study conducted in Boston suggested that blood lead concentrations at 2 years of age were more predictive of cognitive deficits in older children than were later blood lead concentrations or blood lead concentrations measured concurrently with IQ. Therefore, cross-sectional associations between blood lead and IQ in school-age children have been widely interpreted as the residual effects of higher blood lead concentrations at an earlier age or the tendency of less intelligent children to ingest more leaded dust or paint chips, rather than as a causal relationship in older children. Here we analyze data from a clinical trial in which children were treated for elevated blood lead concentrations (20-44 microg/dL) at about 2 years of age and followed until 7 years of age with serial IQ tests and measurements of blood lead. We found that cross-sectional associations increased in strength as the children became older, whereas the relation between baseline blood lead and IQ attenuated. Peak blood lead level thus does not fully account for the observed association in older children between their lower blood lead concentrations and IQ. The effect of concurrent blood level on IQ may therefore be greater than currently believed.

Age Factors↗
PubMed1986

Tardive dyskinesia in young mentally retarded individuals.

The results of a systematic neuroleptic withdrawal study in 38 mentally retarded children, adolescents, and young adults are described. The focus of the study was the occurrence of side effects of chronic neuroleptic treatment: tardive dyskinesia, transient withdrawal dyskinesia, nondyskinetic withdrawal symptoms, and a possible behavioral analogue of withdrawal dyskinesia. Transient side effects were noted in 34% of the subjects, and tardive dyskinesia in an equal proportion. The data suggest that cumulative neuroleptic dose may play a role as a risk factor in the development of severe tardive dyskinesia.

Adolescent↗
PubMed1998

Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial.

BACKGROUND: Systolic hypertension increases the risk of dementia in elderly people. The vascular dementia project, set up in the framework of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial, investigated whether antihypertensive drug treatment could reduce the incidence of dementia. METHODS: Eligible patients had no dementia, were at least 60 years old, and had a blood pressure when seated of 160-219 mm Hg systolic and below 95 mm Hg diastolic. Active treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both drugs, titrated or combined to reduce the systolic blood pressure by at least 20 mm Hg to reach a value below 150 mm Hg. Cognitive function was assessed by the mini mental state examination (MMSE). If the MMSE score was 23 or less, diagnostic tests for dementia were done (DSM-III-R criteria). The cause of dementia was established by the modified ischaemic score with brain imaging or the Hachinski score. FINDINGS: Median follow-up by intention to treat was 2.0 years. Compared with placebo (n=1180), active treatment (n=1238) reduced the incidence of dementia by 50% from 7.7 to 3.8 cases per 1000 patient-years (21 vs 11 patients, p=0.05). The median MMSE score at randomisation was 29 in both treatment groups. At the last available assessment, systolic and diastolic blood pressure were, respectively, 8.3 mm Hg and 3.8 mm Hg lower (p<0.001) in the active-treatment group, but on average the MMSE scores did not change in either group. In the control patients, however, the MMSE decreased (p=0.04) with decreasing diastolic blood pressure, whereas in the active-treatment group MMSE scores improved slightly (p=0.01) with greater reduction in diastolic blood pressure (p=0.002 for between-group difference). INTERPRETATION: In elderly people with isolated systolic hypertension, antihypertensive treatment was associated with a lower incidence of dementia. If 1000 hypertensive patients were treated with antihypertensive drugs for 5 years 19 cases of dementia might be prevented.

Aged↗
PubMed2001

An animal model for the study of the genetic bases of behaviour in men: the multiple marker strains (MMS).

Animal models are often used for preclinical research on the neurobiology of psychiatric disorders. Whereas many are employed to screen new therapeutic agents, few of them are used to study the genetic bases of psychiatric diseases, probably because of the complex genetic determinism underlying quantitative behavioral traits such as mood, personality or intelligence. The present article presents a short review introducing an analysis model using mice: the marker strains model. Using this model it is possible both to display genetic determinism data and to locate some of the chromosomal fragments involved in the regulation of anxiogenic processes. At present it cannot accurately determine the position of one or more genes, but it does provide a valuable means of 'scanning' the genome for an approximation. Through genetic analysis, using the model, an attempt will be made to identify autosomal fragments which may be involved in two behavioural traits: anxiety and chemical-induced seizures. In this paper, after reviewing theoretical aspects of looking for genes involved in behaviour, we will successively introduce studies in genetic topics in psychiatric human studies as well as appropriated behavioural animal studies. Then we will present a genetic model in mice which allows us to locate chromosomal fragments associated with a behavioural trait: multiple marker strains.

Animals↗
PubMed1997

Health On the Net automated database of health and medical information.

With the number of World Wide Web sites growing every day, the problem is not just to find information, but to locate the right piece of information. Current World Wide Web search engines have not resolved this problem as they most often return a long list of documents. The search result is then unusable because of the large number of answers from different domains and topics. Only complex queries may, in a given situation, produce a limited number of potentially relevant documents. To make searches more efficient and usable by common users, we now need intelligent and specialised search engines on the Net [1,2]. Health On the Net Foundation and the Molecular Imaging and Bioinformatics Laboratory at Geneva University Hospital have developed Multi-Agent Retrieval Vagabond on Information Networks (MARVIN), a robot that searches sites and documents specifically related to a given specialised field. One such robot has already been implemented and used for the medical and the 2D electrophoresis domains. Health On the Net Foundation has implemented the corresponding search engines, MedHunt (http://www.hon.ch/cgi-bin/find) for the medical field and 2DHunt (http://www.hon.ch/cgi-bin/2DHunt/find) for the 2D electrophoresis field.

Computer Communication Networks↗
PubMed2025

What is on the Horizon Beyond Platinum and Immunotherapy for Patients With Advanced Non-Small Cell Lung Cancer Without Actionable Genomic Aberrations?

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. While targeted therapy and immunotherapy have transformed first-line management, most patients without actionable genomic alterations (AGAs) will experience disease progression within the first year of their initial treatment. Here, we review pivotal trials, emerging strategies, challenges, and unmet needs for patients with advanced NSCLC without AGAs. Docetaxel with or without ramucirumab is the standard second-line therapy for patients who have progressed after platinum-based chemotherapy and immunotherapy. Targeted therapy is only suitable for patients with specific AGAs. Understanding the hallmarks of cancer immune evasion is key to developing new strategies beyond chemoimmunotherapy. The combination of antiangiogenic agents with immune checkpoint inhibitors (ICIs) has shown mixed results after progression on platinum and ICI. Bispecific antibodies, particularly ivonescimab, have shown encouraging early efficacy in this space. Artificial intelligence-driven pathomics and radiomics tools may help to refine treatment selection in the future. Chimeric antigen receptor T-cell therapy remains investigational. Patients with advanced NSCLC without AGAs who progressed after chemoimmunotherapy have limited treatment options. Novel therapies such as specific antibodies have shown promising results. Future progress will depend on the development of predictive biomarkers and understanding the mechanisms of resistance to ICIs to guide drug development.

Humans↗
PubMed1982

Final report of study on hypertension during pregnancy: the effects of specific treatment on the growth and development of the children.

195 (97.5%) children born to hypertensive women participating in a trial of methyldopa treatment during pregnancy were followed from birth and were extensively examined at the age of 7 1/2 years. The frequency of problems with health, physical or mental handicap, sight, hearing, and behaviour was the same in children of treated and untreated women. Sons of the untreated women were heavier and taller than those of treated women, as were their mothers. Among children of women who entered the trial between 16 and 20 weeks' gestation, sons of untreated women had larger heads than sons of treated women, but there was no difference in mean intelligence quotients. There were no significant differences between the children in the treated and untreated groups in standing and supine blood pressures, or fourteen tests of ability. Methyldopa therefore seems safe to use in pregnancy and is probably preferable to other drugs from the point of view of the neonate and child.

Antihypertensive Agents↗
PubMed2006

A behavioral and cognitive profile of clinically stable HIV-infected children.

OBJECTIVE: The purpose of this research was to characterize behavioral and cognitive profiles of clinically and immunologically stable antiretroviral-experienced HIV-infected children. METHODS: Two hundred seventy-four previously treated HIV-infected children aged 2 to 17 years were assessed for behavioral, developmental, and cognitive functioning. Correlations between neuropsychological measures, age, and CD4 lymphocyte count were investigated. RESULTS: The most common behavioral problems, as measured by the Conners' Parent Rating Scale, were psychosomatic (28%), learning (25%), hyperactivity (20%), impulsive-hyperactive (19%), conduct (16%), and anxiety (8%) problems. Mean Wechsler Intelligence Scale for Children-III scores were less than established population norms; the mean verbal IQ was 85, the mean performance IQ was 90, and the mean full-scale score was 86. Hyperactivity was more frequent in children with a Wechsler Intelligence Scale for Children-III performance IQ of <90. Anxiety problems were more likely in children > or =9 years of age. Children with CD4 counts of <660 cells per mm3 were more likely to be identified as having a conduct disorder. No association was noted between behavioral problems and neuroimaging. CONCLUSIONS: Clinically and immunologically stable HIV-infected children had more frequent behavioral problems and lower developmental and cognitive scores than established childhood norms.

Adolescent↗
PubMed2000

Vulnerability of children and the developing brain to neurotoxic hazards.

For much of the history of toxicology, the sensitivity of the developing organism to chemical perturbation attracted limited attention. Several tragic episodes and new insights finally taught us that the course of early brain development incurs unique risks. Although the process is exquisitely controlled, its lability renders it highly susceptible to damage from environmental chemicals. Such disturbances, as recognized by current testing protocols and legislation such as the Food Quality Protection Act, can result in outcomes ranging from death to malformations to functional impairment. The latter are the most difficult to determine. First, they require a variety of measures to assay their extent. Second, adult responses may prove an inadequate guide to the response of the developing brain, which is part of the reason for proposing additional safety factors for children. Third, neuropsychological tests are deployed in complex circumstances in which many factors, including economic status, combine to produce a particular effect such as lowered intelligence quotient score. Fourth, the magnitude of the effect, for most environmental exposure levels, may be relatively small but extremely significant for public health. Fifth, changes in brain function occur throughout life, and some consequences of early damage may not even emerge until advanced age. Such factors need to be addressed in estimating the influence of a particular agent or group of agents on brain development and its functional expression. It is especially important to consider ways of dealing with multiple risks and their combinations in addition to the prevailing practice of estimating risks in isolation.

Brain↗