Scott J. Richter

Synergy Directed Fractionation of Botanical Medicines: A Case Study with Goldenseal (Hydrastis canadensis)

It is often argued that the efficacy of herbal medicines is a result of the combined action of multiple constituents that work synergistically or additively. Determining the bioactive constituents in these mixtures poses a significant challenge. We have developed an approach to address this challenge, synergy-directed fractionation, which combines comprehensive mass spectrometry profiling with synergy assays and natural products isolation. The applicability of synergy-directed fractionation was demonstrated using the botanical medicine goldenseal (Hydrastis canadensis) as a case study. Three synergists from goldenseal were identified, sideroxylin, 8-desmethyl-sideroxylin, and 6-desmethyl-sideroxylin. These flavonoids synergistically enhance the antimicrobial activity of the alkaloid berberine (also a constituent of H. canadensis) against Staphylococcus aureus by inhibition of the NorA multidrug resistance pump. The flavonoids possess no inherent antimicrobial activity against S. aureus; therefore, they could have been missed using traditional bioactivity-directed fractionation. The flavonoid synergists are present at higher concentration in extracts from H. canadensis leaves, while the antimicrobial alkaloid berberine is present at higher levels in H. canadensis roots. Thus, it may be possible to produce an extract with optimal activity against S. aureus using a combination of goldenseal roots and leaves.

Evaluation of the effectiveness of anterior cruciate ligament injury prevention programme training components: a systematic review and meta-analysis

Background Anterior cruciate ligament (ACL) injury prevention programmes have shown mixed results, which may be due to differing emphasis on training components. The purpose of this study was to (1) quantify the overall and relative duration of each training component encompassed within these programmes and (2) examine the effect of these durations on ACL injury rates. Methods A systematic review was completed and meta-analyses performed on eligible studies to produce a pooled OR estimate of the effectiveness of these programmes. Meta-regression was used to detect any relationship that programme duration and the duration of individual training components had on ACL injury rates. Results 13 studies were included for review. Results of the meta-analyses revealed a significant reduction of injuries after preventative training programmes for all ACL injuries (pooled OR estimate of 0.612, 95% CI 0.44 to 0.85; p=0.004) and for non-contact ACL injuries (OR 0.351, 95% CI 0.23 to 0.54; p<0.001). Results of meta-regression analysis revealed that a greater duration of balance training was associated with a higher injury risk for ACL injury (p=0.04), while greater durations of static stretching was associated with a lower injury risk for non-contact ACL injuries (p=0.04). Conclusions While ACL prevention programmes are successful in reducing the risk of ACL injury, the ideal combination and emphasis of training components within these programmes remains unclear. Evidence indicates that greater emphases on balance training and static stretching may be associated with an increase and decrease in injury risk, respectively.

Complex Data Produce Better Characters

Two studies were conducted to explore the use of complex data in character description and hybrid identification. In order to determine if complex data allow the production of better characters, eight groups of plant systematists were given two classes of drawings of plant parts, and asked to divide them into character states (clusters) in two separate experiments. The first class of drawings consisted only of cotyledons. The second class consisted of triplets of drawings: a cotyledon, seedling leaf, and inflorescence bract. The triplets were used to simulate complex data such as might be garnered by looking at a plant. Each experiment resulted in four characters (groups of clusters), one for each group of systematists. Visual and statistical analysis of the data showed that the systematists were able to produce smaller, more precisely defined character states using the more complex drawings. The character states created with the complex drawings also were more consistent across systematists, and agreed more closely with an independent assessment of phylogeny. To investigate the utility of complex data in an applied task, four observers rated 250 hybrids of Dubautia ciliolata X arborea based on the overall form (Gestalt) of the plants, and took measurements of a number of features of the same plants. A composite score of the measurements was created using principal components analysis. The correlation between the scores on the first principal component and the Gestalt ratings was computed. The Gestalt ratings and PC scores were significantly correlated, demonstrating that assessments of overall similarity can be as useful as more conventional approaches in determining the hybrid status of plants.

Biogeo-optics: particle optical properties and the partitioning of the spectral scattering coefficient of ocean waters

We propose a direct method of partitioning the particulate spectral scattering coefficient of the marine hydrosol based on the concurrent determination of the concentrations of particulate mineral and organic matter (the total mass of optically active scattering material exclusive of water) with the particulate spectral scattering coefficient. For this we derive a Model II multiple linear regression model. The multiple linear regression of the particulate spectral scattering coefficient against the independent variables, the concentrations of particulate inorganic matter and particulate organic matter, yields their mass-specific spectral scattering cross sections. The mass-specific spectral scattering cross section is simply the particle scattering cross section normalized to the particle mass, a fundamental optical efficiency parameter for the attenuation of electromagnetic radiation [Absorption and Scattering of Light by Small Particles, (Wiley-Interscience, 1983), pp. 80-81, 289]. It is possible to infer the optical properties of the suspended matter from the mass-specific spectral scattering cross sections. From these cross sections we partition the particulate spectral scattering coefficient into its major components.

A Method for Determining Equivalence in Industrial Applications

This article considers the problem of determining whether the results of measurements at two different measurement times are equivalent. Quite often in an industrial quality assurance experiment, the goal is to provide evidence of equivalence, rather than difference. Although determining equivalence has long been a staple in biological and chemical applications, it is often useful in industrial situations, such as comparing the characteristics of products measured at different points in time, or produced using different formulations. Methods for assessing equivalence, however, are rarely taught to engineers and other scientists. The purpose of this article is to demonstrate a procedure for assessing equivalence, as well as to demonstrate the inappropriateness of a method commonly used in these situations. The authors suggest that equivalence testing methodology should be among the statistical tools at the disposal of quality and process control engineers.

Poor long-term patient and graft survival after primary percutaneous coronary intervention for acute myocardial infarction due to saphenous vein graft occlusion†

Primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI) due to saphenous vein graft (SVG) occlusion has been associated with poor procedural results and poor short‐term outcomes, but long‐term graft patency and patient survival have not been evaluated. Consecutive patients (n = 2,240) with STEMI treated with primary PCI from 1984 to 2003 were followed for 6.6 years (median). Follow‐up angiography was obtained in 80% of hospital survivors following primary PCI for SVG occlusion at 2.3 years (median). Patients with primary PCI for SVG occlusion (n = 57) vs. native artery occlusion had more prior MI, advanced Killip class, and three‐vessel coronary disease and lower acute ejection fraction (EF). Patients with SVG occlusion had lower rates of TIMI 3 flow post‐PCI (80.7% vs. 93.6%; P = 0.0001), higher in‐hospital mortality (21.1% vs. 8.0%; P = 0.0004), and lower follow‐up EF (49.3% vs. 54.7%; P = 0.055). Culprit SVGs were patent in 64% of patients at 1 year and 56% at 5 years. Late survival was strikingly worse in patients with primary PCI for SVG occlusion vs. native vessel occlusion (49% vs. 76% at 10 years), and SVG occlusion was the second strongest predictor of late cardiac mortality by multivariate analysis (HR = 2.11; 95% CI = 1.38–3.23; P = 0.0006). Patients with STEMI due to SVG occlusion treated with primary PCI have poor acute procedural results, frequent late reocclusion, and very high late mortality. The introduction of new adjunctive therapies (distal protection, thrombectomy, and drug‐eluting stents) may improve short‐term outcomes, but improved long‐term outcomes may require new and more durable revascularization strategies.

Floral Reflectance, Color, and Thermoregulation: What Really Explains Geographic Variation in Thermal Acclimation Ability of Ectotherms?

Adaptive phenotypic plasticity in thermally sensitive traits, that is, thermal acclimation, generally increases with increasing latitude and altitude. The presumed explanation is that high‐latitude/altitude organisms have evolved greater acclimation ability because of exposure to greater temperature fluctuations. Using a conceptual model of the thermal environment during the reproductive season, we tested this hypothesis against an alternative that plasticity is greater because of increased exposure to specific temperatures that strongly select for thermal acclimation. We examined geographic variation in floral reflectance/color plasticity among 29 European populations of a widespread perennial herb, Plantago lanceolata. Individuals partially thermoregulate reproduction through temperature‐sensitive plasticity in floral reflectance/color. Plasticity was positively correlated with latitude and altitude. Path analyses support the hypothesis that the thermal environment mediates these geographic effects. Plasticity declined as seasonal temperature range increased, and it increased as duration of the growing season shortened and as the proportion of time exposed to temperatures favoring thermoregulation increased. Data provide evidence that floral reflectance/color plasticity is adaptive and that it has evolved in response not to the magnitude of temperature variation during the reproductive season but rather to the relative exposure to low temperatures, which favor thermoregulation.

Global sourcing shifts in the U.S. textile and apparel industry: a cluster analysis

Abstract Globalization of the U.S. textile and apparel industry has been significantly spurred in the last decade by trade agreements such as the North American Free Trade Agreement (NAFTA), and the Caribbean Basin Initiative (CBI). In terms of the U.S. textile and apparel manufacturers and retailers, the competitive pressure from markets and consumers has forced many firms to rely increasingly on global sourcing to sustain competitiveness. In the last decade, U.S. textile and apparel manufacturers and retailers have been actively involved in global sourcing to find suppliers who could meet the criteria of low cost, high quality, reliable delivery, quick response time, and flexibility. The purpose of this study is to investigate the changes in U.S. global sourcing patterns for yarn, fabric, and apparel. Cluster analysis is used to analyze trade data in 1993 and 2002 in order to investigate the patterns of U.S. global sourcing of textile and apparel products. Results indicate that U.S. textiles and apparel sourcing patterns have shifted, with a substantially increased emphasis on apparel imports from Mexico and the CBI countries in 2002 as compared to imports from mainland China and Hong Kong in 1993. Sourcing patterns of yarn and fabric indicate that Mexico upgraded its place in U.S. imports of yarn and fabric in 2002. In addition, further longitudinal analysis of U.S. apparel imports from mainland China, Hong Kong, CBI countries, and Mexico, which were the major players in the U.S. global sourcing of apparel, shows that there was a dynamic change in the status of these four regions in terms of their respective percentage shares in U.S. apparel sourcing. The paper concludes that the U.S. textile and apparel global sourcing patterns in last decade reflect the dramatic changes in the competitive and dynamic global textile and apparel business environment. Global sourcing is indeed a fine-tuning business strategy that requires balanced and comprehensive consideration of economic, trade, environmental, and competitive factors.

Nearly exact tests in factorial experiments using the aligned rank transform

A procedure is studied that uses rank-transformed data to perform exact and estimated exact tests, which is an alternative to the commonly used F-ratio test procedure. First, a common parametric test statistic is computed using rank-transformed data, where two methods of ranking-ranks taken for the original observations and ranks taken after aligning the observations-are studied. Significance is then determined using either the exact permutation distribution of the statistic or an estimate of this distribution based on a random sample of all possible permutations. Simulation studies compare the performance of this method with the normal theory parametric F-test and the traditional rank transform procedure. Power and nominal type I error rates are compared under conditions when normal theory assumptions are satisfied, as well as when these assumptions are violated. The method is studied for a two-factor factorial arrangement of treatments in a completely randomized design and for a split-unit experiment. The power of the tests rivals the parametric F-test when normal theory assumptions are satisfied, and is usually superior when normal theory assumptions are not satisfied. Based on the evidence of this study, the exact aligned rank procedure appears to be the overall best choice for performing tests in a general factorial experiment.

Histological alterations in male A/J mice following nose-only exposure to tobacco smoke

The incidence and multiplicity of grossly observed and microscopic lesions of the respiratory tract of A/J mice exposed nose-only to mainstream smoke (50, 200, or 400 mg total particulate matter/m3 from 2R4F cigarettes) was compared to those of filtered air controls. Animals were necropsied at the end of exposure (5 mo) or following 4 or 7 mo of recovery. Lungs were visually inspected for tumors at all necropsies and examined histopathologically at 9 and 12 mo. At 5 mo no tumors were recorded. No significant elevations in tumor incidence or multiplicity were recorded although at 9 mo multiplicity was elevated in the mid-exposure group (0.90 versus 0.55 tumors per animal for controls). At 12 mo, multiplicity was increased over the 9-mo necropsy at all exposures except 200 mg/m3; however, there were no dose-related trends in multiplicity or incidence. Histopathological alterations included hyperplasia, metaplasia, and inflammation of the nose and larynx and proliferative lesions of the lungs. At 9 mo, the multiplicity of focal lung lesions was 1.4 per animal in controls but averaged 1.0 among smoke-exposed groups. There was an inverse relation (p < .059) between smoke concentration and the percentage of hyperplastic lesions at 9 mo. At 12 mo the high-exposure group had slightly increased multiplicity of 2.3 lesions compared with 1.6 among controls, while the percentage of hyperplasic lesions was similar between groups. Nose-only inhalation of mainstream tobacco smoke resulted in chronic inflammatory changes of the respiratory tract yet failed to produce statistically significant changes in tumor incidence or multiplicity.