painPREDICT: first interim data from the development of a new patient-reported pain questionnaire to predict treatment response using sensory symptom profiles.

Objective: Sensory symptom patterns may be useful for predicting treatment response, and, thus, improve individual therapy in patients suffering from neuropathic pain (NeP). Existing screening questionnaires focus predominately on neuropathic mechanisms without consideration of nociceptive mechanisms or mixed pain states. This study aimed to develop a new questionnaire, painPREDICT, using a wide set of patient-reported descriptors potentially associated with neuropathic and nociceptive pain mechanisms, and to explore sensory symptom patterns. Methods: PainPREDICT was constructed based on exploratory (n = 27 patients) and cognitive debriefing interviews (n = 49 patients and nine physicians), across five NeP conditions. The pilot questionnaire was then administered in a non-interventional, cross-sectional, multi-center study to 840 pain patients across the US and Germany. The identification of a sensory symptom pattern was based on hybrid clustering resulting from items standardization followed by principal component analysis. Results: The final questionnaire included 20 items covering: pain intensity, location of pain, course of pain, and sensory symptoms. Most patients participating in the cross-sectional study suffered either from painful diabetic polyneuropathy (n = 330) or radiculopathy (n = 349), fewer from central pain (n = 61) or other types of NeP (n = 100). The hybrid clustering of the new questionnaire data identified three different characteristic sensory symptom profiles in patients with NeP: "Irritable nociceptors", "deafferentation pain", and "pain attacks with nociceptive component". Although some differences in the distribution of the sensory profiles were found, all profiles were represented in all NeP etiology groups. Conclusions: This study set the ground of painPREDICT and showed promising results for its use to categorize patients according to sensory symptom patterns.

Good Practices in Model-Informed Drug Discovery and Development: Practice, Application, and Documentation.

This document was developed to enable greater consistency in the practice, application, and documentation of Model-Informed Drug Discovery and Development (MID3) across the pharmaceutical industry. A collection of "good practice" recommendations are assembled here in order to minimize the heterogeneity in both the quality and content of MID3 implementation and documentation. The three major objectives of this white paper are to: i) inform company decision makers how the strategic integration of MID3 can benefit R&D efficiency; ii) provide MID3 analysts with sufficient material to enhance the planning, rigor, and consistency of the application of MID3; and iii) provide regulatory authorities with substrate to develop MID3 related and/or MID3 enabled guidelines.

Leg and trunk length at 43 years in relation to childhood health, diet and family circumstances; evidence from the 1946 national birth cohort.

BACKGROUND: This is a study of the associations of adult leg and trunk length with early life height and weight, diet, socioeconomic circumstances, and health, and parental height, divorce and death. METHOD: The data used were collected in a longitudinal study of the health, development and ageing of a British national birth cohort (N = 2879 in this analysis) studied since birth in 1946. Multiple regression models were used to investigate the relationships. RESULTS: Adult leg and trunk length were each positively associated with parental height, birthweight, and weight at 4 years. Leg length was associated positively with breastfeeding and energy intake at 4 years. Trunk length was associated negatively with serious illness in childhood and possibly also parental divorce, but not with the dietary data. CONCLUSION: Adult leg length is particularly sensitive to environmental factors and diet in early childhood because that is the period of most rapid leg growth. Trunk growth is faster than leg growth after infancy and before puberty, and may be associated with the effects of serious illness and parental separation because of the child's growing sensitivity to stressful circumstances, as well as the result of the biological effects of illness.

Relationship between asymmetry parameter and hemispheric backscatter ratio: implications for climate forcing by aerosols.

Calculations of direct climate forcing by anthropogenic aerosols commonly use radiative transfer parameters, including asymmetry parameter g. One method of obtaining the asymmetry parameter of a particle population is to convert measured values of the hemispheric-to-total-scatter ratio (backscatter ratio b) into their corresponding g values. We compare a conversion derived from Mie calculations with one derived from the Henyey-Greenstein (HG) phase function to show that the HG method systematically overestimates g for typical size distributions of accumulation-mode aerosols. A delta-Eddington radiative transfer calculation is used to show that a 10% overestimation of g can systematically reduce climate forcing as a result of aerosols by 12% or more. Mie computations are used to derive an empirical relationship between backscatter ratio and asymmetry parameter for log-normal accumulation-mode aerosols. This relationship can be used to convert the backscatter ratio to the asymmetry parameter, independent of geometric mean diameter D(gv) or complex refractive index m, but the conversion requires knowledge of the breadth σ(g) of the size distribution.