A comprehensive review of predictive and prognostic composite factors implicated in the heterogeneity of treatment response and outcome across disease areas.

AIM: To assess and present the current body of evidence regarding composite measures associated with differential treatment response or outcome as a result of patient heterogeneity and to evaluate their consistency across disease areas. METHODS: A comprehensive review of the literature from the last 10 years was performed using three databases (PubMed, Embase and Cochrane). All articles that met the inclusion/exclusion criteria were selected, abstracted and assessed using the NICE level-of-evidence criteria. RESULTS: Forty-nine studies were identified in the data abstraction. Approximately one-third focused on existing composite measures, and the rest investigated emerging composite factors. The majority of studies targeted patients with cancer, cardiovascular disease or psychological disorders. As a whole, the composite measures were found to be disease-specific, but some composite elements, including age, gender, comorbidities and health status, showed consistency across disease areas. To complement these findings, common individual factors found in five previous independent disease-specific literature assessments were also summarised, including age, gender, treatment adherence and satisfaction, healthcare resource utilisation and health status. CONCLUSIONS: Composite measures can play an important role in characterising heterogeneity of treatment response and outcome in patients suffering from various medical conditions. These measures can help clinicians to better distinguish between patients with high likelihood to respond well to treatment and patients with minimal chances of positive therapeutic outcomes. Herein, the individual factors identified can be used to develop novel predictive or prognostic composite measures that can be applicable across disease areas. Reflecting these cross-disease measures in clinical and public health decisions has the distinctive appeal to enable targeted treatment for patients suffering from multiple medical conditions, which may ultimately yield significant gains in individual outcomes, population health and cost-effective resource allocation.

Empirical results of using back-propagation neural networks to separate single echoes from multiple echoes.

Empirical results illustrate the pitfalls of applying an artificial neural network (ANN) to classification of underwater active sonar returns. During training, a back-propagation ANN classifier learns to recognize two classes of reflected active sonar waveforms: waveforms having two major sonar echoes or peaks and those having one major echo or peak. It is shown how the classifier learns to distinguish between the two classes. Testing the ANN classifier with different waveforms of each type generated unexpected results: the number of echo peaks was nor the feature used to separate classes.

Naloxone potentiates contractile responses to epinephrine in isolated canine arteries.

The beneficial pressor effects of naloxone in shock have been associated with existing adrenergic systems and in particular with circulating epinephrine. Vascular interactions among alpha adrenergic receptor agents, naloxone, and selected opioids were investigated. The addition of pharmacologic concentrations of the opiate antagonist naloxone enhanced contractile responses to lower doses of epinephrine by more than 100% in isolated renal interlobar arteries. Naloxone lowered the EC50 for both epinephrine and norepinephrine but the magnitude of enhanced responses were much greater for epinephrine. Responses in the presence of naloxone to more selective alpha agonists, phenylephrine and clonidine, were also much less. The enhanced contraction cannot be demonstrated in the absence of added catecholamine and is eliminated by alpha but not by beta adrenergic blockade. Dose responses for naloxone provided an EC50 (micromolar) above those reported for known opiate receptors. Representative mu (morphiceptin), delta (DADL), and kappa (dynorphin 1-9) receptor agonists were ineffective in altering the EC50 for naloxone. Responses opposite to naloxone could be generated with pharmacological additions of another kappa opioid, dynorphin 1-8. This effect was also accomplished without shifting the EC50 for naloxone to the right, suggesting dynorphin and naloxone operate via separate mechanisms. The (+) stereoisomer of naloxone was as or more effective than (-) naloxone, adding support for a nontraditional or nonopiate receptor mechanism. Corticosterone produced responses indistinguishable from naloxone. These pharmacological steroid-like responses to naloxone are used to suggest a hypothesis based upon modulation of extra-neuronal uptake and/or adrenergic receptor desensitization mechanisms.

The NBS Alloy Data Center: Description of Index to the Literature.

Computerized listings of 10,000 research papers, indexed at the Alloy Data Center, are now being made available in two forms. In the first, the Permuted Materials Index, all records are arranged alphabetically by chemical symbol. Records referring to alloys or compounds are listed under each of the constituent elements. In the second, the Author Index, all papers are listed alphabetically by first author in three groupings: the first, the NMR papers; the second, the soft x-ray papers; and the third, a broad group of papers that have been of general interest to the Alloy Physics Section. The magnetic tape on which the indexed file is stored will be made available at a future date.

Relevance of Knight Shift Measurements to the Electronic Density of States.

The Knight shift, K , measures the magnetic hyperfine field at the nucleus produced by the conduction electrons which are polarized in a magnetic field. Knight shifts are often dominated by the Pauli term and, in its most simple form, can be written as K = 〈 a 〉 χ p . Here χ p is the conduction electron Pauli spin susceptibility which depends on the density of states at the Fermi level, N(E f ), and 〈a〉 is an average magnetic hyperfine coupling constant associated with the wave function character at the nucleus, ∣ψ F (0)∣2, for conduction electrons at the Fermi surface. The Knight shift therefore provides, through 〈a〉, insight into the wave-function character associated with N(E F ). Calculations of 〈a〉 involving an averaging over k-space have been attempted for a few simple metals up to the present time. For alloys and intermetallic compounds, rather different 〈a〉's are experimentally observed for different local environments, indicating that K samples the variation in local wave-function character, or a variation in local density of states. There is no unique way of separating the local variation of N(E F ) from ∣ψ F ∣(0)∣2. In this article the methods developed for relating K to the electronic properties for most of the types of cases encountered in the literature are reviewed. We discuss "simple" metals including problems of orbital magnetism and changes in K caused by electronic transitions such as melting. Knight shifts and their temperature dependence in metals and intermetallic compounds involving unfilled d shells, are discussed. We give estimates of atomic hyperfine fields due to single electrons, appropriate to those cases where problems due to electronic configurations do not make deductions from experiment too ambiguous. A density of states curve calculated for Cu is given, showing the relative importance of s-p, and d character for that metal. In a qualitative sense this Cu curve implies such information for other transition metals. We discuss alloy solid solutions for the cases where a "rigid" band model might be used to explain the results, and for cases where local effects have to be taken into account. The charge oscillation and RKKY approaches and their limitations are reviewed for cases of dilute nonmagnetic and d- or f-type impurities.