The other GMP: good manufacturing practice and its importance in the validation of constructed pharmaceutical facilities

The work reported is part of an ongoing PhD study prompted by the particular difficulties encountered when two very different quality cultures interact (in this case Pharmaceutical industry clients and Construction industry providers). Pharmaceutical facilities have particular needs for their production requirements. Stringent regulations are set by regulatory bodies such as the Medicines and Healthcare products Regulatory Agency (MHRA) (in the UK) and the Food and Drugs Administration (FDA) in the US. This creates special problems of quality when it comes to the commissioning, validation and hand-over of the building, as it appears to be at odds with the rather less demanding quality systems that are normally accepted in the construction sector. The aim of the research is to model an acceptable process for incorporating these stringent validation requirements into the design, procurement and construction processes. There is little or no specific academic literature on the subject, though the trades and professional press (particularly in the USA) provide some normative comment on the problem area. The main academic grounding of the research is in Systems Theory and empirical data is being collecting using a multiple case study approach. Research data was collected from a number of pharmaceutical facility construction case studies and was used to test and inform a best practice model of facility validation. The qualitative methods of participant and direct observation were used as the main information gathering tools. The paper reports on the regulatory expectations that influence the construction of projects of this type and the impact on the best practice model of validation

RRS Discovery Cruise 243, 11th October to 22nd November 1999. Sensory Biology in the Deep-Sea: Anatomy, Physiology, and Molecular Biology

RRS Discovery cruise 243 had two principal objectives: to collect deep-sea animals for a variety of biological studies ranging from physiology to molecular biology, and to deploy benthic landers. The landers are described in Section 9.1, and the midwater and benthic trawling in Section 9.2. A complete list of the stations worked, with times, latitudes and longitudes, is given in Section 10, and a track chart for the whole cruise is shown in Section 11. Trawling was conducted first and foremost in order to provide specimens required for work associated with NERC grant GR3/B1212 “Analysis of light-induced interactions in the deep-sea: bioluminescence and its relation to vision, reflectance and fluorescence” to Professor Peter Herring, Dr Julian Partridge, and Dr Peter Shelton. Of equal importance to the success of the cruise, however, was the provision of biological samples for a range of inter-related studies. Descriptions of these studies are given in Section 9.3. Throughout the cruise a narrative (Section 6) was compiled to document, in diary format, the main scientific activities on board ship. It also records information about factors which affected work, such as the weather, and problems with equipment. The narrative is more or less a list of notes rather than proper prose, and was written during the cruise, documenting events as they were planned, as they unfolded, or after they had happened. In consequence, the tenses of verbs tend to vary in a haphazard way, for which I apologise. During the cruise, the Discovery “Rough Log” of biological specimens was maintained by Professor Peter Herring. A précis of some of the information from the Rough Log is incorporated into the narrative as a record of some of the most common, and some of the most unusual, animals that were collected. This is necessarily a biased record. Nevertheless, it may be useful to others planning or conducting similar cruises to the areas worked during D243, particularly those targeting the pelagic macrofauna. As the narrative shows, D243 was plagued by problems with the main winch. At one stage, early in the cruise, the severity of these problems made it likely that the cruise would have to be terminated prematurely, without any trawling having been undertaken. That this situation was reversed is due to the determination and hard work of the RVS technicians who were on board the ship. To them, Phil Taylor (RVS Technical Liaison Officer/TLO), Kevin Smith (RVS Mobilisation Officer/MO), Paul Duncan, and Rhys Roberts, we are much indebted: without their labours the cruise would not have succeeded in the way it ultimately did. Inevitably, the “science time” of the cruise was affected by the winch problems (see Section 8) and was contributory to a decision not to work the slope of the African continent, which had been part of the original cruise directive. This was, however, to some extent compensated by the generally stable weather conditions in the work area. Although we encountered conditions more extreme than are indicated in the ‘Africa Pilot’ for the region during October/November (anticipated average wind force 3), at no time was work stopped by poor weather. This in itself partly justifies the relatively long passage time to the work area. The main reason for working in the region, however, was the high diversity and abundance of midwater and benthic macrofauna in this region of upwelling and high surface water productivity. This, in combination with the trawling methods used, which included the use of the relatively large RMT25 net and a closing cod end on the RMT8 net, ensured that the requirements of the scientific personnel for specimens were well met. The scientific complement of the cruise consisted of 23 people, ranging from graduate students to professors, from five countries and eleven institutions. In addition, the cruise also hosted a team from the BBC Natural History Unit, who were on board to film for the “The Blue Planet”, a television series about the seas which is due for release in 2001. That this diverse group (who are listed, with their contact details, in Section 2) worked so well together, and were steadfastly cheerful firstly in the face of the winch problems, and later in the face of the relentlessness of trawling and catch processing, is very much to their credit. As Principal Scientist on D243 I am extremely grateful for their hard work and support in the run-up to the cruise, during the time at sea, and in its aftermath. In particular I would like to single out for thanks Ben Boorman and Nigel Merrett who, as scientific day and night watch leaders, ensured that the fishing and the supply of specimens continued without a break. D243 was also notable for one other event: it was Peter Herring’ last cruise before his retirement from the Southampton Oceanography Centre. Without a doubt, none of the participants on D243 would have been there but for Peter, such has been his impact on ocean going biology. Indeed, the format of D243 very much follows the successful formula developed by him on numerous previous cruises, including some to the Cape Verde region of the West African upwelling. If a cruise report can be dedicated, this is dedicated to him

In-situ defect detection systems for R2R flexible PV barrier films

Film processing procedures by means of Roll-to-Roll (R2R) for barrier coatings can often result in PV barrier films being manufactured with significant quantities of defects, which resulting in lower efficiency and a short life span. In order to improve the process yield and product efficiency it is desirable to develop an inspection system that can detect transparent barrier film defects in the production line during the film processing. Off-line detection of defect in transparent PV barrier films is difficult and time consuming. Consequently implementing an accurate in-situ defects inspection system in the production environment is even more challenging, since the requirements on positioning, fast measurement, long term stability and robustness against environmental disturbance are demanding. This paper reports on the development and deployment of two in-situ PV barrier films defect detection systems, one of them is based on wavelength scanning interferometry (WSI) and the other one is based on White Light Channeled Spectral Interferometry (WLCSI), and the integration into an R2R film processing line in the Centre for Process Innovation (CPI). The paper outlines the environmental vibration strategy for both systems and the developed auto-focussing methodology for WSI. The systems have been tested and characterised and initial results compared to laboratory-based instrumentation are presented

In-situ defect detection systems for R2R flexible PV films

The atomic layer deposition technique (ALD) is used to apply a thin (40-100 nm thick) barrier coating of Al2O3 on polymer substrates for flexible PV cells, to minimise and control the degradation caused by water vapour ingress. However, defects appearing on the film surfaces during the Al2O3 ALD growth have been seen to be highly significant in deterioration of the PV module efficiency and lifespan [1]. In order to improve the process yield and product efficiency, it is desirable to develop an inspection system that can detect transparent barrier film defects in the production line during film processing. Off-line detection of defects in transparent PV barrier films is difficult and time consuming. Consequently, implementing an accurate in-situ defects inspection system in the production environment is even more challenging, since the requirements on positioning, fast measurement, long term stability and robustness against environmental disturbance are demanding. For in-situ R2R defects inspection systems the following conditions need to be satisfied by the inspection tools. Firstly the measurement must be fast and have no physical contact with the inspected film surface. Secondly the measurement system must be robust against the environmental disturbance inspection. Finally the system should have sub-micrometre lateral resolution and nanometre vertical resolution in order to be able to distinguish defects on the film surface. Optical interferometry techniques have the potentially to be used as a solution for such application. However they are extremely sensitive to environmental noise such as mechanical vibration, air turbulence and temperature drift. George [2] reported that a single shot interferometry system “FlexCam” developed by 4D Technology being used currently to detect defects for PV barrier films manufactured by R2R technology. It is robust against environmental disturbances; but it has a limited vertical range, which is restricted by the phase ambiguity of the phase shift interferometry. This vertical measurement range (a few hundreds nanometres) is far less than the normal vertical range of defects (a few micrometres up to a few tens micrometres). It is not possible to detect the majority of defects in the R2R flexible PV barrier films

Researching education outcomes in Burundi, Malawi, Senegal and Uganda: using participatory tools and collaborative approaches : The Improving Learning Outcomes in Primary Schools (ILOPS) Project | Project methodology

In January 2008, ActionAid, Dr Karen Edge (IOE) and partners in Burundi, Malawi, Uganda and Senegal studied the role of parents and teachers in enhancing learning outcomes. The Improving Learning Outcomes in Primary Schools (ILOPS) Project was supported by the Quality Education in Developing Countries Initiative of the William and Flora Hewlett Foundation in partnership with the Bill & Melinda Gates Foundation. Findings from the ILOPS Project are presented in three separate briefs exploring teacher quality, parental participation and, this paper, exploring our tools and approaches. This paper, primarily designed for practitioner audiences, outlines the participatory research methodology designed by Dr Karen Edge and the strategies employ the methods with a team of 53 senior educational leaders from participating countries. The strategies were designed to bring teams of non-researchers together, to build national-level team capacity and collaboration and support their work in the field by collaborating with all participants to design the overall conceptual framework and methods of the study. In this paper, we provide details on the development and implementation of our approach as well as the lessons learned throughout the process for others interested in following similar approaches. This approach has been employed within several other IOE project, led by Dr Edge. In addition, the approach has influenced the work of ActionAid and other participating stakeholders

Quasi-hydrostatic intracluster gas under radiative cooling

Quasi-hydrostatic cooling of the intracluster gas is studied. In the quasi-hydrostatic model, work done by gravity on the inflow gas with dP \neq 0, where P is the gas pressure, is taken into account in the thermal balance. The gas flows in from the outer part so as to compensate the pressure loss of the gas undergoing radiative cooling, but the mass flow is so moderate and smooth that the gas is considered to be quasi-hydrostatic. The temperature of the cooling gas decreases toward the cluster center, but, unlike cooling flows with dP = 0, approaches a constant temperature of \sim 1/3 the temperature of the non-cooling ambient gas. This does not mean that gravitational work cancels out radiative cooling, but means that the temperature of the cooling gas appears to approach a constant value toward the cluster center if the gas maintains the quasi-hydrostatic balance. We discuss the mass flow in quasi-hydrostatic cooling, and compare it with the standard isobaric cooling flow model. We also discuss the implication of \dot{M} for the standard cooling flow model.Comment: 5 pages, 1 figure, accepted for publication in A&

XMM-Newton Observation of a Distant X-ray Selected Cluster of Galaxies at z=1.26 with Possible Cluster Interaction

We report on the XMM-Newton (XMM) observation of RXJ1053.7+5735, one of the most distant (z = 1.26) X-ray selected clusters of galaxies, which also shows an unusual double-lobed X-ray morphology, indicative of possible cluster-cluster interaction. The cluster was discovered during our ROSAT deep pointings in the direction of the Lockman Hole. The XMM observations were performed with the European Photon Imaging Camera (EPIC) during the performance verification phase. Total effective exposure time was ~ 100 ksec. The best fit temperature based on a simultaneous fit of spectra from the all EPIC cameras is 4.9(+1.5/-0.9) keV. Metallicity is poorly constrained even using the joint fit of all spectra, with an upper limit on the iron abundance of 0.62 solar. Using the best fit model parameters, we derived a bolometric luminosity of L(bol) = 3.4x10^44 h_{50}^-2 erg /s. Despite the fact that it was observed at fairly large off-axis angle, the temperature errors are much smaller compared with those of typical measurements based on ASCA or Beppo-Sax observations of z > 0.6 clusters, demonstrating the power of the XMM for determining the X-ray temperature for high-z clusters. The measured temperature and luminosity show that one can easily reach the intrinsically X-ray faint and cool cluster regime comparable with those of z ~ 0.4 clusters observed by past satellites. The new cluster temperature and L(bol) we have measured for RXJ1053.7+5735 is consistent with a weak/no evolution of the L(bol) - Tx relation out to z ~ 1.3, which lends support to a low Omega universe, although more data-points of z > 1 clusters are required for a more definitive statement. The caution has to be also exercised in interpreting the result, because of the uncertainty associated with the dynamical status of this cluster.Comment: Accepted for pubblication in A&A. 7 figures (One color figure is changed to black and white.

Particle acceleration in cooling flow clusters of galaxies: the case of Abell 2626

It has recently been proposed a theoretical model which accounts for the origin of radio mini-halos observed in some cooling flow clusters as related to electron re-acceleration by MHD turbulence (Gitti, Brunetti & Setti 2002). The MHD turbulence is assumed to be frozen into the flow of the thermal ICM and thus amplified in the cooling flow region. Here we present the application of this model to a new mini-halo candidate, the cluster A2626, and compare the results with those obtained for the mini-halo in the Perseus cluster. We present VLA data at 330 MHz and 1.5 GHz of the diffuse radio emission observed in A2626, and we show that its main properties can be explained by the model. We find that the power necessary for the re-acceleration of the relic electron population is only a factor ~ 0.7% of the maximum power that can be extracted by the cooling flow (as estimated on the basis of the standard model). We also discuss the observational properties of known mini-halos in connection with those of host clusters, showing that the radio power of mini--halos increases with the maximum power of cooling flows. This trend is expected in the framework of the model. Possible effects of new Chandra and XMM-Newton estimates of $\dot{M}$ on this trend are considered: we conclude that even if earlier derived cooling rates were overestimated, cooling flow powers are still well above the radio powers emitted by mini-halos.Comment: 12 pages, 11 figures, accepted for publication in Astronomy & Astrophysic

Three-dimensional brain reconstruction of in vivo electrode tracks for neuroscience and neural prosthetic applications

The brain is a densely interconnected network that relies on populations of neurons within and across multiple nuclei to code for features leading to perception and action. However, the neurophysiology field is still dominated by the characterization of individual neurons, rather than simultaneous recordings across multiple regions, without consistent spatial reconstruction of their locations for comparisons across studies. There are sophisticated histological and imaging techniques for performing brain reconstructions. However, what is needed is a method that is relatively easy and inexpensive to implement in a typical neurophysiology lab and provides consistent identification of electrode locations to make it widely used for pooling data across studies and research groups. This paper presents our initial development of such an approach for reconstructing electrode tracks and site locations within the guinea pig inferior colliculus (IC) to identify its functional organization for frequency coding relevant for a new auditory midbrain implant (AMI). Encouragingly, the spatial error associated with different individuals reconstructing electrode tracks for the same midbrain was less than 65 μm, corresponding to an error of ~1.5% relative to the entire IC structure (~4–5 mm diameter sphere). Furthermore, the reconstructed frequency laminae of the IC were consistently aligned across three sampled midbrains, demonstrating the ability to use our method to combine location data across animals. Hopefully, through further improvements in our reconstruction method, it can be used as a standard protocol across neurophysiology labs to characterize neural data not only within the IC but also within other brain regions to help bridge the gap between cellular activity and network function. Clinically, correlating function with location within and across multiple brain regions can guide optimal placement of electrodes for the growing field of neural prosthetics

FUSE search for 10^5-10^6 K gas in the rich clusters of galaxies Abell 2029 and Abell 3112

Recent Chandra and XMM X-ray observations of rich clusters of galaxies have shown that the amount of hot gas which is cooling below ~1 keV is generally more modest than previous estimates. Yet, the real level of the cooling flows, if any, remains to be clarified by making observations sensitive to different temperature ranges. As a follow-up of the FUSE observations reporting a positive detection of the OVI doublet at 1032, 1038 Angstrom in the cluster of galaxies Abell 2597, which provided the first direct evidence for ~3x10^5 K gas in a cluster of galaxies, we have carried out sensitive spectroscopy of two rich clusters, Abell 2029 and Abell 3112 (z~0.07) located behind low HI columns. In neither of these clusters could we detect the OVI doublet, yielding fairly stringent limits of ~27 Msun yr-1 (Abell 2029) and ~25 Msun yr-1 (Abell 3112) to the cooling flow rates using the 10^5-10^6 K gas as a tracer. The non-detections support the emerging picture that the cooling-flow rates are much more modest than deduced from earlier X-ray observations.Comment: Astronomy & Astrophysics, in pres