Engineering automated systems for pharmaceutical manufacturing: quality, regulations and business performance

The pharmaceutical sector is very heavily regulated Drug safety regulations form one of the pillars of this regulation. The manufacture of pharmaceuticals is carried out in an environment of onerous regulatory requirements, often from several national and international regulatory bodies. The quality systems operated by drug manufacturers and their regulatory practices have an important impact on product quality. The quality and regulatory requirements apply not only to handling of the medicinal products, but also to the physical and electronic systems used in the manufacture of those products, and extend to automated systems used to support quality assurance operations. Design, development, building and support of such systems are ultimately the responsibility of the drug manufacturer. The quality and regulatory requirements for automated systems are passed down the supply chain to suppliers. In the last two decades of the 20th century there has been a proliferation in the use of computerised and automated systems for use in, or to support manufacturing. Correspondingly, regulatory requirements have been imposed on the manufacturing industry. This work used survey research and factor analysis to establish relationships between quality and regulatory practices, and between both quality and regulatory practices and business performance for suppliers of automated systems into the pharmaceutical market. A survey instrument and an administration strategy were developed from a review of the literature. It was established empirically that quality practices and regulatory practices were strongly related. Specific facets of quality practices and regulatory practices were found to have had a significant impact on both market share and competitiveness expectations and also profit and sales expectations. Differences in practices and performance were established for various levels of automation complexity and criticality, where criticality was a function of the risk the respondent’s system posed to the manufacture of their customer’s products

Electron microscope study of film nucleation

Nucleation and growth of iron and vanadium thin films to observe polymorphic transformation using electron microscop

Impact on procurement and training by research on the interaction design of medical devices

We present a case study of how research can influence practice in the procurement of healthcare technology based on the CHI+MED project. CHI+MED is concerned with interaction design and the safety of medical devices. It has combined scientific research on underlying human error, and the development of engineering tools and techniques based on this science. It has also included a strong stakeholder engagement strand, aiming to ensure that the research has impact. In particular CHI+MED research has directly informed a UKP 2.5 million procurement decision at a Welsh health board, leading to safer equipment being bought. It provided the evidence to support one kind of device being rated more highly due to its ease of safe use. Our research is also the basis of a new approach to evidence-based procurement based on proactively analysing error logs of existing devices. The logs are analysed to determine the strengths and weaknesses of devices to provide evidence for future decisions. It has also contributed to a programme to ensure software that helps reduce errors is used. CHI+MED research has also fed into training programmes. Our research is actively preventing patients being unnecessarily harmed and also saving staff time from not having to work with hard to use technology, so ultimately saving money

A polarizable interatomic force field for TiO2_2 parameterized using density functional theory

We report a classical interatomic force field for TiO$_2$, which has been parameterized using density functional theory forces, energies, and stresses in the rutile crystal structure. The reliability of this new classical potential is tested by evaluating the structural properties, equation of state, phonon properties, thermal expansion, and some thermodynamic quantities such as entropy, free energy, and specific heat under constant volume. The good agreement of our results with {\em ab initio} calculations and with experimental data, indicates that our force-field describes the atomic interactions of TiO$_2$ in the rutile structure very well. The force field can also describe the structures of the brookite and anatase crystals with good accuracy.Comment: Accepted for publication in Phys. Rev. B; Changes from v1 include multiple minor revisions and a re-write of the description of the force field in Section II

Combination of Immunohistochemistry and Ploidy Analysis to Assist Histopathological Diagnosis of Molar Diseases

Background Differential diagnosis between hydropic abortion, partial mole and complete mole is still a challenge for pathologists but really important for patient management. Material and Method In this study, we have evaluated 111 products of conception from the first trimester. Histological analysis was made according to the main diagnostic histopathological features described in the literature and the cases were categorized in hydropic abortus (HA), partial mole (PM) and complete mole (CM). Immunohistochemistry was performed using monoclonal antibody against p57 kip protein a putative paternally imprinted inhibitor gene and DNA ploidy was analysed in all cases by image cytometry. Results All 23 HAs presented a diploid DNA content and were p57 kip2 positive. From the 28 CMs, 12 cases (43%) were diploid and 16 cases (57%) were tetraploid but no expression of p57 kip2 was found with positive internal controls. From the 60 PMs, 58 cases were positive for p57 kip2 expression and 53 cases (88%) were triploid, 6 cases (10%) tetraploid and 1 case (2%) diploid. Conclusion This study on 111 cases of early pregnancies confirms the usefulness of immunohistochemistry and cytometry but demonstrates the importance of the combination of both techniques to assist histology for the best reliable diagnosis

Boulder City, Nevada revenue generating analysis

Boulder City (City) is unique in the State of Nevada as being a non-gaming city, maintaining a controlled growth ordinance, and steadfastly holding to its “small town” values and character. The City has been facing budgetary challenges as future expenditures are anticipated to continually exceed revenues if current services levels are maintained. Indeed, fiscal reviews indicate the City has been transferring contingency monies between funds to cover overages for the past several fiscal years. This “robbing Peter to pay Paul” methodology may offer a temporary solution to the shortage but may be detrimental as a long term solution

Nuclear actin-related proteins at the core of epigenetic control

Nuclear Actin-Related Proteins (ARPs) and actin combine as heterodimers to bind a large helicase subunit and form a core complex essential to the assembly and function of most chromatin remodeling and modifying machines. They are the most common shared subunits of these large and diverse assemblies in eukaryotes. We recently argued that most nuclear ARPs evolved directly from actin prior to the divergence of the eukaryotic kingdoms and did not evolve from pre-existing ARPs.2 Arabidopsis plants defective in nuclear ARP4, ARP5, ARP6 or ARP7 have extreme developmental phenotypes. Our recent publication demonstrates that ARP5-defective plants are not only dwarfed and have aberrant cell sizes, but are also hypersensitive to mutagenic agents that cause double strand DNA breaks.5 In Smith et al.6 we show that ARP6-defective plants, in addition to their extreme developmental phenotypes like small organs and early flowering, present an apparent Phosphate Starvation Response with strong morphological and molecular phenotypes. Herein, we interpret our latest data in the light of a hypothesis stating that in addition to their roles in overcoming DNA compaction that affects basal gene expression and silencing, nuclear ARP-containing chromatin complexes exert primary epigenetic control over high-level regulatory factors. © 2010 Landes Bioscience

Hijacking membrane transporters for arsenic phytoextraction

Arsenic is a toxic metalloid and recognized carcinogen. Arsenate and arsenite are the most common arsenic species available for uptake by plants. As an inorganic phosphate (Pi) analog, arsenate is acquired by plant roots through endogenous Pi transport systems. Inside the cell, arsenate is reduced to the thiol-reactive form arsenite. Glutathione (GSH)-conjugates of arsenite may be extruded from the cell or sequestered in vacuoles by members of the ATP-binding cassette (ABC) family of transporters. In the present study we sought to enhance both plant arsenic uptake through Pi transporter overexpression, and plant arsenic tolerance through ABC transporter overexpression. We demonstrate that Arabidopsis thaliana plants overexpressing the high-affinity Pi transporter family members, AtPht1;1 or AtPht1;7, are hypersensitive to arsenate due to increased arsenate uptake. These plants do not exhibit increased sensitivity to arsenite. Co-overexpression of the yeast ABC transporter YCF1 in combination with AtPht1;1 or AtPht1;7 suppresses the arsenate-sensitive phenotype while further enhancing arsenic uptake. Taken together, our results support an arsenic transport mechanism in which arsenate uptake is increased through Pi transporter overexpression, and arsenic tolerance is enhanced through YCF1-mediated vacuolar sequestration. This work substantiates the viability of coupling enhanced uptake and vacuolar sequestration as a means for developing a prototypical engineered arsenic hyperaccumulator. © 2012 Elsevier B.V