Quality risk analysis in a cGMP environment: multiple models for comprehensive failure mode identification during the computer system lifecycle

Pharmaceutical quality systems use various inputs to ensure product quality and prevent failures that might have patient consequences. These inputs are generally data from failures that have already occurred, for example process deviations or customer complaints. Risk analysis techniques are well-established in certain other industries and have become of interest to pharmaceutical manufacturers because they allow potential quality failures to be predicted and mitigating action taken in advance of their occurring. Failure mode and effects analysis (FMEA) is one such technique, and in this study it was applied to implement a computerized manufacturing execution system in a pharmaceutical manufacturing environment. After introduction, the system was monitored to detect failures that did occur and these were analyzed to determine why the risk analysis method failed to predict them. Application of FMEA in other industries has identified weaknesses in predicting certain error types, specifically its dependence on other techniques to model risk situations and its poor analysis of non-hardware risks, such as human error, and this was confirmed in this study. Hierarchical holographic modeling (HHM), a technique for identifying risk scenarios in wide-scope analyses, was applied subsequently and identified additional potential failure modes. The technique for human error rate prediction (THERP) has previously been used for the quantitative analysis of human error risk and the event tree from this technique was adapted and identified further human error scenarios. These were input to the FMEA for prioritization and mitigation, thereby strengthening the risk analysis in terms of failure modes considered.     

CERA: a collaborative environment reference architecture for interoperable CWE systems

In this paper, we present the collaborative environment reference architecture (CERA) with the aim of supporting collaborative work environment (CWE) interoperability. The vision of CERA is to support users who are engaged in common collaborative spaces with similar work processes to work and collaborate seamlessly together, despite their use of proprietary CWE tools and systems. The underlying CERA concepts, design principles, and models are discussed, as well as the architectural decisions made as a result of the extended requirements analysis exercise. Furthermore, we present results from the Ecospace () project as an example of a CERA instantiation which focuses on facilitating users collaborating across different CWE systems, namely BSCW, NetWeaver, and BC. We conclude with future research and implementation directions.     

Cigarette smoking patterns among young adults aged 18-24 years in the United States.

Most tobacco control programs focus on prevention for children or cessation for adults. Little is known about cigarette smoking among young adults. This study examined sociodemographic variables associated with current, daily, heavy, and light smoking among young adults in the United States. Data from the 1998-1999 Tobacco Use Supplement to the Current Population Survey (TUS-CPS) were used to examine cigarette smoking patterns and correlates of smoking among 15,371 young adults aged 18-24 years. We found that 26% of young adults were current smokers, 20% were daily smokers, and 8% were former smokers. Current smoking rates were higher among American Indians/Alaska Natives (33%) and Whites (31%) than among other racial/ethnic groups. Compared with white-collar workers, blue-collar and service workers were more likely to report current and daily smoking. Blue-collar workers also were more likely to report heavy smoking (OR = 1.97). The unemployed (those in the labor force but not currently working) and those reporting an annual household income of less than US$20,000 were more likely to report current, daily, and heavy smoking, compared with those not in the labor force and those reporting an annual household income of $20,000 or more, respectively. Young adults not currently enrolled in school were more than twice as likely to report current (OR = 2.36) and daily (OR = 2.90) smoking, compared with those currently enrolled in school. Differential cigarette smoking patterns by race/ethnicity, occupation, employment status, household income, and school enrollment status should be considered when developing interventions to reduce smoking among young adults.     

Fault tolerance versus performance metrics for robot systems

The incorporation of fault tolerance techniques into robot systems improves the reliability, but also increases the hardware and computational requirements in the overall system. It is not always clear how to evaluate the merit, or ‘effectiveness’ of different fault tolerance approaches for a given application. In this paper, we present a new set of performance criteria designed to measure and compare the effectiveness of robot fault tolerance strategies. The measures, which are designed to evaluate fault tolerance/performance/cost tradeoffs, can also be used to evaluate pure performance or pure fault tolerance strategies. We show their usefulness using a variety of proposed fault tolerance approaches in the literature, focusing on multiprocessor control architectures.     

Disruption of human eyeblink conditioning after central cholinergic blockade with scopolamine.

72 human volunteers received saline, a low dose of oral scopolamine (0.6 mg), a high dose of oral scopolamine (1.2 mg), or a peripheral analog (glycopyrrolate). They then underwent classical conditioning of the eyeblink response to a tone CS and a corneal airpuff unconditioned stimulus/stimuli (UCS) in a delay conditioning paradigm. There was a dose-related decline in acquisition of the CR. These drug-induced conditioning deficits were similar to those previously reported in rabbit eyeblink conditioning and could not be attributed to such nonassociative factors as changes in auditory thresholds to the tone CS, magnitude of reflexive blinks to the airpuff UCS, or to changes in spontaneous blink rates. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stability of DNA origami nanoarrays in cell lysate

Scaffolded DNA origami, a method to create self-assembled nanostructures with spatially addressable features, has recently been used to develop water-soluble molecular chips for label-free RNA detection, platforms for deterministic protein positioning, and single molecule reaction observatories. These applications highlight the possibility of exploiting the unique properties and biocompatibility of DNA nanostructures in live, cellular systems. Herein, we assembled several DNA origami nanostructures of differing shape, size and probes, and investigated their interaction with lysate obtained from various normal and cancerous cell lines. We separated and analyzed the origami-lysate mixtures using agarose gel electrophoresis and recovered the DNA structures for functional assay and subsequent microscopic examination. Our results demonstrate that DNA origami nanostructures are stable in cell lysate and can be easily separated from lysate mixtures, in contrast to natural, single- and double-stranded DNA. Atomic force microscope (AFM) and transmission electron microscope (TEM) images show that the DNA origami structures are fully intact after separation from cell lysates and hybridize to their targets, verifying the superior structural integrity and functionality of self-assembled DNA origami nanostructures relative to conventional oligonucleotides. The stability and functionality of DNA origami structures in cell lysate validate their use for biological applications, for example, as programmable molecular rafts or disease detection platforms.     

Embedding off-the-shelf filter in PDMS chip for microbe sampling

Filtration for microfluidic sample-collection devices is desirable for sample selection, concentration, preprocessing, and manipulation, but microfabricating the required sub-micrometer structures is an elaborate process. This article presents a simple method to integrate filters in polydimethylsiloxane (PDMS) devices to sample microorganisms in aqueous environments. An off-the-shelf membrane filter with 0.22-μm pores was embedded in a PDMS layer and sequentially bound with other PDMS channel layers. No leakage was observed during filtration. This device was validated by concentrating a large amount of biomass, from 15 × 10⁷ to 3 × 10⁸ cells/ml of cyanobacterium Synechocystis in simulated sample water with consistent performance across devices. The major advantages of this method are low cost, simple design, straightforward fabrication, and robust performance, enabling wide-utility of chip-based devices for field-deployable operations in environmental microbiology.     

Effect of pasture versus indoor feeding regimes on the yield,composition, ripening and sensory characteristics of Maasdam cheese

Maasdam cheese was manufactured from standardized milk derived from each of three feeding systems: grass (GRA), grass and clover pasture (CLO), and indoor feeding of total mixed ration (TMR). Pasture‐derived cheeses had significantly lower L* (whiteness) and higher b* values (yellowness) compared to TMR‐derived cheeses. Acetate levels were significantly lower in CLO and butyrate levels significantly higher in TMR compared to the other cheeses. Grass‐fed cheese had significantly higher scores for smooth texture, ivory colour and shiny appearance compared to TMR. The influence of feed type was minimal on cheese yield, composition and on glycolysis, lipolysis and proteolysis during ripening.