From Kohn-Sham to Many-Electron Energies via Step Structures in the Exchange-Correlation Potential.

Accurately describing excited states within Kohn-Sham (KS) density functional theory (DFT), particularly those which induce ionization and charge transfer, remains a great challenge. Common exchange-correlation (xc) approximations are unreliable for excited states owing, in part, to the absence of a derivative discontinuity in the xc energy (Δ), which relates a many-electron energy difference to the corresponding KS energy difference. We demonstrate, analytically and numerically, how the relationship between KS and many-electron energies leads to the step structures observed in the exact xc potential in four scenarios: electron addition, molecular dissociation, excitation of a finite system, and charge transfer. We further show that steps in the potential can be obtained also with common xc approximations, as simple as the LDA, when addressed from the ensemble perspective. The article therefore highlights how capturing the relationship between KS and many-electron energies with advanced xc approximations is crucial for accurately calculating excitations, as well as the ground-state density and energy of systems which consist of distinct subsystems.

Electron localisation in static and time-dependent one-dimensional model systems.

The most direct signature of electron localisation is the tendency of an electron in a many-body system to exclude other same-spin electrons from its vicinity. By applying this concept directly to the exact many-body wavefunction, we find that localisation can vary considerably between different ground-state systems, and can also be strongly disrupted, as a function of time, when a system is driven by an applied electric field. We use this measure to assess the well-known electron localisation function (ELF), both in its approximate single-particle form (often applied within density-functional theory) and its full many-particle form. The full ELF always gives an excellent description of localisation, but the approximate ELF fails in time-dependent situations, even when the exact Kohn-Sham orbitals are employed.

How Interatomic Steps in the Exact Kohn-Sham Potential Relate to Derivative Discontinuities of the Energy.

Accurate density functional calculations hinge on reliable approximations to the unknown exchange-correlation (xc) potential. The most popular approximations usually lack features of the exact xc potential that are important for an accurate prediction of the fundamental gap and the distribution of charge in complex systems. Two principal features in this regard are the spatially uniform shift in the potential, as the number of electrons infinitesimally surpasses an integer, and the spatial steps that form, for example, between the atoms of stretched molecules. Although both aforementioned concepts are well known, the exact relationship between them remained unclear. Here we establish this relationship via an analytical derivation. We support our result by numerically solving the many-electron Schrödinger equation to extract the exact Kohn-Sham potential and directly observe its features. Spatial steps in the exact xc potential of a full configuration-interaction (FCI) calculation of a molecule are presented in three dimensions.

Liver disease associated with exposure to 1,1,1-trichloroethane.

1,1,1-trichloroethane is a halogenated hydrocarbon solvent commonly used in industry because of its supposed lack of hepatotoxicity. Nonetheless, animal studies performed by several independent groups have shown the solvent to induce fat deposition, vacuolar degeneration, and centrilobular necrosis, changes similar to those seen after exposure to carbon tetrachloride, albeit of a much reduced magnitude, in animals exposed to the agent. Four patients with fatty liver disease whose work entailed substantial exposure to this agent were seen at the University of Pittsburgh (Pa). Based on this clinical experience, we believe that 1,1,1-trichloroethane should be reconsidered as an agent with potential hepatotoxicity in man.

Delay in P300 latency in patients with organic solvent exposure.

Event-related potentials were examined in 12 individuals with a history of organic solvent exposure and in 19 nonexposed controls. The latencies of the N250 and P300 components of the auditory event-related potential were significantly delayed in the solvent-exposed patients compared with those in normal controls. Amplitudes of the N100, P200, and N250 components were larger in the solvent-exposed group, but the P300 amplitude did not differentiate between groups. A comparison with data from clinically stable outpatient schizophrenics indicated that P300 latencies were longer in the solvent-exposed group. Within the exposed group, P300 latency was positively correlated with length of exposure. The delay in N250 and P300 provides evidence that solvent exposure slows central nervous system mechanisms that evaluate and/or process relevant stimuli. The assessment of event-related potentials may be an especially useful way to evaluate central nervous system integrity in persons who have had a neurotoxic exposure.

Assessment of attention and memory efficiency in persons with solvent neurotoxicity.

Memory and attention were evaluated in 40 persons with a history of organic solvent exposure and 40 demographically similar controls. Exposed subjects, in comparison to controls, had reduced digit spans, were deficient at learning new information, and recall on a Brown-Peterson distractor test was especially low following a 30-sec interference interval. If original learning was considered, long-term recall was similar for both groups. On a test of sustained attention, the Continuous Performance Test, exposed subjects became less accurate over successive blocks, a pattern opposite to that seen in control subjects. The data suggest that the memory impairment following solvent exposure may result from deficient allocation of attentional resources due to the inability to deal effectively with an increase in processing load.

Giant-cell interstitial pneumonia and hard-metal pneumoconiosis. A clinicopathologic study of four cases and review of the literature.

We report four cases of giant-cell interstitial pneumonia that occurred in association with exposure to hard metals. All patients presented with chronic interstitial lung disease and had open-lung biopsies that revealed marked interstitial fibrosis, cellular interstitial infiltrates, and prominent intraalveolar macrophages as well as giant cells displaying cellular cannibalism. We also review the literature to determine the sensitivity and specificity of giant-cell interstitial pneumonia for hard-metal pneumoconiosis. Although hard-metal pneumoconiosis may take the form of usual interstitial pneumonia, desquamative interstitial pneumonia, and giant-cell interstitial pneumonia, the finding of giant-cell interstitial pneumonia is almost pathognomonic of hard-metal disease and should provoke an investigation of occupational exposure.

Psychiatric symptomatology in persons with organic solvent exposure.

This study investigated psychiatric symptomatology, self-concept, locus of control, and daily events in persons with a history of exposure to mixtures of organic solvents. Exposed subjects were more likely than controls to report depression, anxiety, fatigue, confusion, and somatic concerns, which in turn were associated with certain exposure-related variables (e.g., cacosmia). There were no differences between the groups in self-concept, locus of control, or ratings of daily hassles and uplifts. Exposed persons may be able to accurately identify what they perceive as changes that are due to the exposure (e.g., anxiety) without attributing these specific adverse outcomes to dispositional variables.

An hierarchical location-allocation model for primary health care delivery in a developing area.

Location-allocation models can play an important role in making primary health care facilities more accessible to rural populations in the developing world. Traditional models, however, have failed to deal realistically with the fact that health care systems are hierarchical in nature, and that benefits and utilization decline with distance. In this paper, an hierarchical location-allocation model in which benefits accrue to facility level and decline exponentially with distance is presented as a possible approach to ameliorating problems of rural accessibility to health care in Third World settings. The model is subjected to sensitivity analysis with reference to data for Salcette Taluka, Goa, India. The analysis suggests that the traditional P-median model may be a much less appropriate solution to the problem than a simple strategy of locating facilities from the highest to the lowest level in centers of strictly decreasing population.

Gulf War illnesses: causation and treatment.

Soldiers returning from the Gulf War in 1991 described a range of symptoms, including some consistent with the chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity. Well-defined adverse health events attributable to service in the Gulf occurred. However, controlled epidemiological studies in Gulf War veterans and controls describe significant excesses of symptoms that were not clearly associated with pathologic disease. At least 12% of veterans currently receive some form of disability from the Department of Veterans Affairs. A number of reports outline theories proposed to explain the excess, but few are scientifically supported. Management guidelines for this spectrum of disorders resembles that of many of "emerging overlap syndromes," including multiple chemical sensitivity, chronic fatigue syndrome, and fibromyalgia. They include the establishment of a trusting doctor-patient relationship, negotiations around a common ground of scientific and etiologic beliefs, non-labeling of the disorder, and work toward recovery in the absence of clear etiologic answers.

Case-control study of idiopathic pulmonary fibrosis and environmental exposures.

The authors conducted a matched case-control study of interstitial lung disease (ILD) using a self-administered questionnaire. All cases in the practice of two pulmonary specialists were identified. Cases were excluded if they were thought to have occupational exposures as a contributor, hypersensitivity pneumonitis or sarcoidosis, or some other well-recognized cause. Three controls were matched by sex and age (one year) as identified through orthopedic surgeons at the same institutions. Two rounds of a questionnaire were mailed; 17 cases (37.7%) and 94 controls (32.4%) responded to the questionnaire, although many of the case addresses were no longer valid. Individuals with ILD were 16.0 times as likely to report mold exposure and 11.1 times as likely to report silica as were controls in their workplace. Odds ratios associating ILD with moisture indicators in the home were in the same range as previously published associations between such indicators and wheezing. ILD may have environmental and occupational causes that warrant more systematic exploration.

Building-associated pulmonary disease from exposure to Stachybotrys chartarum and Aspergillus versicolor.

The authors present an outbreak of disease associated with exposure to Stachybotrys chartarum and Aspergillus species. A courthouse and two associated office buildings had generated discomfort among employees for two years since initial occupancy. Multiple interventions had been unsuccessful An initial evaluation of 14 individuals identified three with potential asthma and three with symptoms consistent with interstitial lung disease. A clinical screening protocol to identify individuals who should be removed from work identified three likely and seven possible cases of building-related asthma. Detailed environmental and engineering assessments of the building identified major problems in mechanical system design, building construction, and operational strategies leading to excess moisture and elevated relative humidities. Moisture-damaged interior surfaces in both buildings were contaminated with S. chartarum, A. versicolor, and Penicillium species. Aspergillus species, especially A. versicolor, at concentrations of 10(1) to 10(4)/m3 dominated the indoor air under normal operating conditions. Bulk samples also revealed large quantities of Stachybotrys. A questionnaire survey of the three case and two control buildings documented between three- and 15-fold increases in symptoms. A nested case-control study suggested emphysematous-like disease in individuals meeting questionnaire definitions for cases. Replication of analysis strategies used in similar previous investigations suggested an association between worsening symptoms and decreased diffusing capacity of the lung. Performance on neuropsychological measures was similar for both cases and controls, although workers with symptoms reported increased levels of current but not past psychiatric symptomatology. Chemical analyses demonstrated the presence of satratoxins G and H. Cytotoxic laboratory analyses demonstrated the presence of agents with biological effectiveness in bulk materials. No association was seen between IgE or IgG antibodies and the presence of disease. This outbreak represents a likely human response to inhaled fungal toxins in indoor environments. Moisture indoors represents a public health issue currently inadequately addressed by building, health, or housing codes.

Pulmonary disease associated with cafeteria flooding.

An illness among office workers, consisting of cough, fever, chills, muscle aches, and chest tightness was associated with water leaks from a cafeteria. Mean single breath carbon-monoxide diffusing capacity (DLCO) of cases differed significantly from that of non-cases. There was a significant decrease in the percent of predicted DLCO with increasing number of symptoms. Testing for precipitating antibodies to microbial agents found in the building revealed no differences between cases and non-cases. DLCO is an appropriate cross-sectional instrument for field investigations of building-associated respiratory disease.

Noxious fumes in a medical center: chemical and psychological aspects.

A group of operating room personnel at a medical center in Connecticut reported severe respiratory irritation manifested by either proxysmal cough or throat irritation suggestive of a noxious fume exposure, 13 April 1994. However, persistent complaints on 14 April 1994 were significantly different and more suggestive of a psychological reaction. By careful interviewing, physical examination, toxicological assays, and epidemiological investigation, the true nature of a mixed physiological and psychological episode was delineated. Enlightened management policy enabled rapid restoration of return to work with minimal economic loss.

Indoor air quality.

Complaints in modern buildings have been attributed to inadequate ventilation for the last 20 years. Few data exist to support this claim. In fact, few studies have actually looked at ventilation and complaints at the same time. These missing studies indicate a failure of three groups of professionals, physicians and health scientists, architects and engineers, and scientists knowledgeable in exposure assessment, to study the topic together. This article will provide a conceptual framework for each of the three approaches and give some guidance on preventing problems.

Clinical diagnosis and management of building-related illness and the sick-building syndrome.

The diagnostic and therapeutic strategies for patient management are discussed in the context of formal clinical criteria for the work-relatedness of disease. The lack of systematic methods to document the presence of various forms of building-related disease is emphasized as being a fundamental problem in clinical practice.

Environmental tobacco smoke and the sick building syndrome.

Environmental tobacco smoke is of serious concern in ventilated spaces both for comfort because of its odor properties and for health reasons. Although it has not been demonstrated as the primary cause in complaints, it is frequently seen as a contributing factor. Recirculation of air with ETS, without filtration or air-washing, may in fact lead to complaints, although at an unknown frequency. Finally, the contributions of ETS to the sick building syndrome is documented, although its extent is currently unknown.

Risk factors for nonoccupational organophosphate pesticide poisoning.

The 535 reports of nonoccupational/nonagricultural poisoning with malathion in the Pesticide Incident Monitoring System (PIMS), a data base maintained by the Environmental Protection Agency, were coded and classified to describe the occurrence and to determine risk factors for poisoning. Between 1966 and 1980, 335 (63%) of reported incidents were associated with at least one symptomatic person, with a total of 670 persons exposed. Home exposures accounted for 92% of reports and arose from improper use and labeling problems in 61% and 3% of reports, respectively. Seventeen reports (3%) were associated with commercial extermination at home. One third of the 18 fatalities from malathion were unintentional and, therefore, preventable. The relative risks of fatal outcome from suicidal intent and labeling problems were, respectively 41 (P less than 10[-6]) and 4.8 (P = .09). When data from a previously coded data set on diazinon were added, the odds ratios were 20 and 6.7 (both P less than .0003). This suggests that public health measures aimed at safer use of pesticides outside the workplace are needed and that the PIMS data are a valuable source of epidemiological data on pesticide poisoning.