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A new approach to empirical intermolecular and conformational potential energy functions. I. Description of model and derivation of parameters.

An empirical potential energy function based on the interactions of the electrons and nuclei in molecules has been developed and tested. The potential energy of interaction is approximated by the sum of the coulombic interactions between all point charge centers (electrons and nuclei), an exponential repulsion to represent electron-electron overlap repulsion, and an R(-6) (R = distance) attraction to simulate dispersion and other attractive energies between the heavy atom fragments of the molecules. The parameters of the potential energy function have been determined from experimental gas-phase and crystal data.The results indicate that both intramolecular and intermolecular interaction energies can be treated with the same set of parameters. In comparison to other empirical interaction potentials now in use, there are fewer independent parameters, there is no need for intrinsic torsional potentials to obtain the correct rotational barriers, and there is no need for special hydrogen bonding functions to account for the directionality and energetics of hydrogen bonding.

Journal Article↗

A new approach to empirical intermolecular and conformational potential energy functions. II. Applications to crystal packing, rotational barriers, and conformational analysis.

An empirical potential energy function based on the interactions of electrons and nuclei (EPEN) has been tested on molecules other than those used for its parameterization. The results indicate that this energy function is able to predict reliably the lowest energy conformations, the potential energy differences between conformations, rotational barrier heights, and dipole moments for a series of alkanes, amines, alcohols, and carbohydrates. Crystal packing studies on n-hexane, n-octane, methylamine, methanol, and alpha-d-glucose, using this same potential, indicate that it is also reliable for calculating intermolecular interaction energies and low-energy orientations.

1-Propanol↗

Nosocomial pneumonia : rationalizing the approach to empirical therapy.

Nosocomial pneumonia or hospital-acquired pneumonia (HAP) causes considerable morbidity and mortality. It is the second most common nosocomial infection and the leading cause of death from hospital-acquired infections. In 1996 the American Thoracic Society (ATS) published guidelines for empirical therapy of HAP. This review focuses on the literature that has appeared since the ATS statement. Early diagnosis of HAP and its etiology is crucial in guiding empirical therapy. Since 1996, it has become clear that differentiating mere colonization from etiologic pathogens infecting the lower respiratory tract is best achieved by employing bronchoalveolar lavage (BAL) or protected specimen brush (PSB) in combination with quantitative culture and detection of intracellular microorganisms. Endotracheal aspirate and non-bronchoscopic BAL/PSB in combination with quantitative culture provide a good alternative in patients suspected of ventilator-associated pneumonia. Since culture results take 2-3 days, initial therapy of HAP is by definition empirical. Epidemiologic studies have identified the most frequently involved pathogens: Enterobacteriaceae, Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus ('core pathogens'). Empirical therapy covering only the 'core pathogens' will suffice in patients without risk factors for resistant microorganisms. Studies that have appeared since the ATS statement issued in 1996, demonstrate several new risk factors for HAP with multiresistant pathogens. In patients with risk factors, empirical therapy should consist of antibacterials with a broader spectrum. The most important risk factors for resistant microorganisms are late onset of HAP (>/=5 days after admission), recent use of antibacterial therapy, and mechanical ventilation. Multiresistant bacteria of specific interest are methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter calcoaceticus-baumannii, Stenotrophomonas maltophilia and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Each of these organisms has its specific susceptibility pattern, demanding appropriate antibacterial treatment. To further improve outcomes, specific therapeutic options for multiresistant pathogens and pharmacological factors are discussed. Antibacterials developed since 1996 or antibacterials with renewed interest (linezolid, quinupristin/dalfopristin, teicoplanin, meropenem, new fluoroquinolones, and fourth-generation cephalosporins) are discussed in the light of developing resistance.Since the ATS statement, many reports have shown increasing incidences of resistant microorganisms. Therefore, one of the most important conclusions from this review is that empirical therapy for HAP should not be based on general guidelines alone, but that local epidemiology should be taken into account and used in the formulation of local guidelines.

Anti-Bacterial Agents↗

Incorporating biological information as a prior in an empirical bayes approach to analyzing microarray data.

Currently the practice of using existing biological knowledge in analyzing high throughput genomic and proteomic data is mainly for the purpose of validations. Here we take a different approach of incorporating biological knowledge into statistical analysis to improve statistical power and efficiency. Specifically, we consider how to fuse biological information into a mixture model to analyze microarray data. In contrast to a standard mixture model where it is assumed that all the genes come from the same (marginal) distribution, including an equal prior probability of having an event, such as having differential expression or being bound by a transcription factor (TF), our proposed mixture model allows the genes in different groups to have different distributions while the grouping of the genes reflects biological information. Using a list of about 800 putative cell cycle-regulated genes as prior biological knowledge, we analyze a genome-wide location data to detect binding sites of TF Fkh1. We find that our proposal improves over the standard approach, resulting in reduced false discovery rates (FDR), and hence it is a useful alternative to the current practice.

Journal Article↗

Quantifying the qualitative: an empirical poetic approach.

Two studies are described which take a psychometric approach to a qualitative phenomenon. A computational analysis of poetry was conducted. Using a lexicon programme, patterns emerged generally supporting the idea of a poet's everchanging thematic preoccupations. Using a multimedia educational software package, presenting the poetical phrase accompanied by visual stimuli had a substantial effect on the appreciation of the poet's meaning. These novel methodological approaches might stimulate further work in this area.

Humans↗

Do osteopathic physicians differ in patient interaction from allopathic physicians? An empirically derived approach.

Colleges of osteopathic medicine teach osteopathic principles, which provide a different approach to and interaction with patients than principles taught in allopathic medical schools. The authors examined whether osteopathic primary care physicians' interactions with patients reflect the principles of osteopathic medicine when compared with allopathic physicians' interactions. The principles of osteopathic medicine were adapted to elements that could be measured from an audio recording. This 26-item index was refined with two focus groups of practicing osteopathic physicians. Fifty-four patient visits to 11 osteopathic and 7 allopathic primary care physicians in Maine for screening physicals, headache, low back pain, and hypertension were recorded on audiotape and were dual-abstracted. When the 26-item index of osteopathic principles was summed, the osteopathic physicians had consistently higher scores (11 vs. 6.9; P = .01) than allopathic physicians, and visit length was similar (22 minutes vs. 20 minutes, respectively). Twenty-three of the 26 items were used more commonly by the osteopathic physicians. Osteopathic physicians were more likely than allopathic physicians to use patients' first names; explain etiologic factors to patients; and discuss social, family, and emotional impact of illnesses. In this study, osteopathic physicians were easily distinguishable from allopathic physicians by their verbal interactions with patients. Future studies should replicate this finding as well as determine whether it correlates with patient outcomes and satisfaction.

Female↗

Choice of antihypertensive medication regimen.

Because increased peripheral vascular resistance is one of the primary pathophysiologic processes involved in hypertension in elderly persons, drugs that decrease peripheral resistance are conceptually preferred in elderly hypertensive patients. Adequate clinical studies are needed, however, to determine if this conceptual approach is superior to an empiric approach. Data available to date still indicate that diuretics are effective agents to treat elderly hypertensive patients.

Aged↗

Approaches to developing new anxiolytics and antidepressants.

The empirical approach to new treatments for anxiety and depression has been to test series of compounds that resemble medications in current use until one is found with similar actions but with fewer side effects. With the explosion of knowledge in neurobiology, it is becoming possible to develop treatments aimed more precisely at specific links in the chain of mood dysregulation. Examples of this informed approach include agonists for limbic but not cortical benzodiazepine receptors; compounds to stabilize serotonergic and noradrenergic transmission; and drugs that act on intracellular signals, such as the calcium ion and cyclic AMP. This article reviews neurobiologically informed approaches to developing new medications for anxiety and depression and discusses some of the innovative treatments that are emerging from such a strategy.

Anti-Anxiety Agents↗