HM: 10: Mahan is Not Enough

The Proceedings of a Conference on the Works of Sir Julian Corbett and Admiral Sir Herbert Richmond.https://digital-commons.usnwc.edu/usnwc-historical-monographs/1009/thumbnail.jp

Multivariate statistical process control of an industrial-scale fed-batch simulator

This article presents an improved batch-to-batch optimisation technique that is shown to be able to bring the yield closer to its set-point from one batch to the next. In addition, an innovative Model Predictive Control technique is proposed that over multiple batches, reduces the variability in yield that occurs as a result of random variations in raw material properties and in-batch process fluctuations. The proposed controller uses validity constraints to restrict the decisional space to that described by the identification dataset that was used to develop an adaptive multi-way partial least squares model of the process. A further contribution of this article is the formulation of a bootstrap calculation to determine confidence intervals within the hard constraints imposed on model validity. The proposed control strategy was applied to a realistic industrial-scale fed-batch penicillin simulator, where its performance was demonstrated to provide improved consistency and yield when compared with nominal operation

A review of the factors involved in older people's decision making with regard to influenza vaccination: a literature review

Aims and objectives. The aim of this paper was to develop an understanding of the factors involved in older people's decision making with regard to influenza vaccination to inform strategies to improve vaccine uptake and reduce morbidity and mortality. Background. Influenza is a major cause of morbidity and mortality world-wide. In the UK, it accounts for 3000–6000 deaths annually; 85% of these deaths are people aged 65 and over. Despite this, and the widespread and costly annual government campaigns, some older people at risk of influenza and the associated complications remain reluctant to take advantage of the offer of vaccination. Methods. A review of the English language literature referring to older people published between 1996 and 2005 was the method used. Inclusion and exclusion criteria were identified and applied. Results. The majority of the literature was quantitative in nature, investigating personal characteristics thought to be predictors of uptake, such as age, sex, co-morbidity, educational level, income and area of residence. However, there was little discussion of the possible reasons for the significance of these factors and conflict between findings was often evident, particularly between studies employing different methodologies. Other factors identified were prior experience, concerns about the vaccine, perceived risk and advice and information. Relevance to clinical practice. The wealth of demographic information available will be useful at a strategic level in targeting groups identified as being unlikely to accept vaccination. However, the promotion of person-centred ways of working that value the health beliefs, attitudes, perceptions and subjective experiences of older people is likely to be more successful during individual encounters designed to promote acceptance. Without more research in investigating these concepts, our understanding is inevitably limited

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque

There are substantial differences across species in the organisation and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration 'thin' spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the expression of Kv3.1b in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labelled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons

Modern day monitoring and control challenges outlined on an industrial-scale benchmark fermentation process

This paper outlines real-world control challenges faced by modern-day biopharmaceutical facilities through the extension of a previously developed industrial-scale penicillin fermentation simulation (IndPenSim). The extensions include the addition of a simulated Raman spectroscopy device for the purpose of developing, evaluating and implementation of advanced and innovative control solutions applicable to biotechnology facilities. IndPenSim can be operated in fixed or operator controlled mode and generates all the available on-line, off-line and Raman spectra for each batch. The capabilities of IndPenSim were initially demonstrated through the implementation of a QbD methodology utilising the three stages of the PAT framework. Furthermore, IndPenSim evaluated a fault detection algorithm to detect process faults occurring on different batches recorded throughout a yearly campaign. The simulator and all data presented here are available to download at www.industrialpenicillinsimulation.com and acts as a benchmark for researchers to analyse, improve and optimise the current control strategy implemented on this facility. Additionally, a highly valuable data resource containing 100 batches with all available process and Raman spectroscopy measurements is freely available to download. This data is highly suitable for the development of big data analytics, machine learning (ML) or artificial intelligence (AI) algorithms applicable to the biopharmaceutical industry

A scale-down mimic for mapping the process performance of centrifugation, depth and sterile filtration

In the production of biopharmaceuticals disk-stack centrifugation is widely used as a harvest step for the removal of cells and cellular debris. Depth filters followed by sterile filters are often then employed to remove residual solids remaining in the centrate. Process development of centrifugation is usually conducted at pilot-scale so as to mimic the commercial scale equipment but this method requires large quantities of cell culture and significant levels of effort for successful characterization. A scale-down approach based upon the use of a shear device and a bench-top centrifuge has been extended in this work towards a preparative methodology that successfully predicts the performance of the continuous centrifuge and polishing filters. The use of this methodology allows the effects of cell culture conditions and large-scale centrifugal process parameters on subsequent filtration performance to be assessed at an early stage of process development where material availability is limited

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations