Evolution and structure of drying material bridges of pharmaceutical excipients: studies on a microscope slide

An experimental procedure was developed to study directly the process by which liquid bridges between small particles in a granule form and solidify. The evolution of saturated solutions of such pharmaceutical excipients as lactose and mannitol in a liquid bridge was studied on a system situated on a microscope slide. Solidification and crystallization kinetics and phase composition during and immediately following bridge formation were observed directly. It was shown that bridges on the microscope slide and in the granule behave very much the same regardless of the different length and diffusion-scales of the two systems.We found that solid bridge formation takes place in several consecutive but distinct steps. In the case of lactose, considerable shrinkage of the initial liquid bridge takes place prior to the onset of crystallization. Further bridge solidification at ambient conditions occurs via simultaneous crystallization and vitrification within minutes. As a result, a “solid” bridge usually contains both a crystalline and a non-crystalline phase, the crystalline phase being predominately α-lactose monohydrate. Most of the non-crystalline phase eventually converts to crystalline β-lactose but the process may take many hours or even days. Results for this process are compared for samples obtained from different manufacturers of commercially available lactose. In the case of mannitol, different polymorphic forms crystallize as the drying/crystallization process progresses. A formed “solid” bridge usually contains several polymorphs of mannitol. The relevance of the behavior of the two model systems (pure lactose and pure mannitol) to a real granulation and tabletting process is discussed.     

Children's choice of playground equipment: Development of methodology for integrating user preferences into environmental engineering.

Determined whether preference scaling techniques could be used to aid engineering system design. Children's play equipment was selected as the design area. Paired comparison and rank-order methods were used to determine whether 48 3rd-4th graders had preferences for different types of play equipment; whether these preferences were reliable over time; and whether actual use of play equipment was predictable from the preference scales developed. Photographic stimuli were used for the scaling and were presented to Ss. The frequency of use of play equipment was also determined using time-lapse photography. Results indicate that (a) Ss did have stable and reliable preferences for play equipment and (b) these preferences were correlated with actual usage of the equipment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aggregation‐Prone Amyloid‐β⋅CuII Species Formed on the Millisecond Timescale under Mildly Acidic Conditions

Metal ions and their interaction with the amyloid beta (Aβ) peptide might be key elements in the development of Alzheimer's disease. In this work the effect of Cu^II on the aggregation of Aβ is explored on a timescale from milliseconds to days, both at physiological pH and under mildly acidic conditions, by using stopped‐flow kinetic measurements (fluorescence and light‐scattering), ¹H NMR relaxation and ThT fluorescence. A minimal reaction model that relates the initial Cu^II binding and Aβ folding with downstream aggregation is presented. We demonstrate that a highly aggregation prone Aβ ? Cu^II species is formed on the sub‐second timescale at mildly acidic pH. This observation might be central to the molecular origin of the known detrimental effect of acidosis in Alzheimer's disease.     

An automated time–frequency approach for ultrasonic monitoring of fastener hole cracks

Angle beam ultrasonic inspection methods are well established for detection and sizing of fatigue cracks originating from fastener holes, and have recently been applied to in situ monitoring of such cracks using permanently attached transducers. Prior work utilizing a dual angle beam method has demonstrated the efficacy of an energy ratio algorithm for detection and sizing of cracks in open holes. This energy ratio is a measure of how much a crack opens under load, and is the ratio of transmitted energy for the specimen under tensile loading to the energy under no load, normalized by the ratio computed for the undamaged hole. Considered here is an extension of this method which utilizes multiple time and frequency windows of the received signals for computing the energy ratio with the goal of achieving the earliest possible detection of cracking. These windows allow different spatial regions to be selectively interrogated, and windows corresponding to the actual crack geometry should be more effective at detecting the crack. An automated algorithm is developed and implemented to permit multiple time–frequency windows to be effectively analyzed without requiring manual interpretation. Results are shown which indicate that cracking in open holes can be detected significantly earlier in the fatiguing process compared to the previously implemented full-window energy ratio method. Integral to the method is the assumption that there is a significant change in crack closure as a function of load.     

The Role of Feedback Information for Calibration and Attunement in Perceiving Length by Dynamic Touch.

Two processes have been hypothesized to underlie improvement in perception: attunement and calibration. These processes were examined in a dynamic touch paradigm in which participants were asked to report the lengths of unseen, wielded rods differing in length, diameter, and material. Two experiments addressed whether feedback informs about the need for reattunement and recalibration. Feedback indicating actual length induced both recalibration and reattunement. Recalibration did not occur when feedback indicated only whether 2 rods were of the same length or of different lengths. Such feedback, however, did induce reattunement. These results suggest that attunement and calibration are dissociable processes and that feedback informs which is needed. The observed change in variable use has implications also for research on what mechanical variables underlie length perception by dynamic touch. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulus–target compatibility for reaching movements.

Reaction time, movement time, and initial direction of reaching movements toward a target in left or right hemispace were measured. In Experiment 1, the target of movement and hand had to be selected; movements toward the imperative stimulus were initiated faster than movements toward the alternate target, and ipsilateral reaches were initiated faster than contralateral reaches. In Experiment 2, the difference between ipsilateral and contralateral reaches disappeared when no selection of the hand had to occur. In Experiment 3, no target had to be selected, and only a stimulus-hand compatibility effect appeared. The results reveal different compatibility effects (stimulus-target, stimulus-hand, target-hand), implying that participants exploit different correspondences, depending on the degrees of freedom of the action. The notion of compatibility effects relating to movement targets offers a new perspective on the negative Simon effect and it questions the general concept of response codes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

When Science Isn't Enough: Wilhelm Hueper, Robert A. M. Case, and the Limits of Scientific Evidence in Preventing Occupational Bladder Cancer

A recent outbreak of occupational bladder cancer in a Buffalo, New York, factory confirmed the carcinogenicity of ortho-toluidine, an aromatic amine that had first been implicated in human bladder cancer cases decades earlier. Events leading to this outbreak replicated the history of numerous earlier bladder cancer outbreaks among workers exposed to beta-naphthylamine and benzidine, two other aromatic amines that were widely used in the dye and rubber industries and that have been responsible for bladder cancer outbreaks in the United States, Germany, Switzerland, England, France, Italy, Austria, Czechoslovakia, the former Soviet Union, Poland, and China. The historic development of scientific knowledge of occupational bladder cancer prefigured many debates that later occurred around other environmental carcinogens; two of the giants of occupational medicine, Wilhelm Hueper and Robert A. M. Case, played seminal roles in the study of these chemicals. Examination of the history of worker exposure to aromatic amines and the subsequent development of bladder cancer at Du Pont, Allied Chemical, and other U.S. manufacturers demonstrates that these carcinogens were regulated only after cancer epidemics were recognized. Production and use of aromatic amines continues in developing countries; these nations will inevitably experience similar outbreaks unless steps are taken to eliminate exposure to these deadly chemicals. This paper chronicles the history of occupational bladder cancer in the United States, highlighting the roles of Hueper and Case in occupational cancer investigation and prevention.