Simplifying manufacturing and control of dual vector AAV therapies

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The training of professional linguists in the United Kingdom

SIGLEAvailable from British Library Document Supply Centre- DSC:DX92431 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Self-Hypnosis for Intrapartum Pain management (SHIP) in pregnant nulliparous women: a randomised controlled trial of clinical effectiveness

Abstract Objective: (Primary): to establish the effect of antenatal group self-hypnosis for nulliparous women on intra-partum epidural use Design: Multi-method RCT Setting: Three NHS Trusts Population: Nulliparous women not planning elective caesarean, without medication for hypertension and without psychological illness. Methods: Randomisation at 28-32 weeks gestation to usual care, or to usual care plus brief self-hypnosis training (two x 90 minute groups at around 32 and 35 weeks gestation; daily audio self-hypnosis CD). Follow up at two and six weeks postnatal. Main outcome measures:- Primary: epidural analgesia Secondary: associated clinical and psychological outcomes; economic analysis. Results: 680 women were randomised. There was no statistically significant difference in epidural use: 27.9% (intervention), 30.3% (control), odds ratio (OR) 0.89 (95% confidence interval (CI): 0.64 to 1.24), or in 27 of 29 pre-specified secondary clinical and psychological outcomes. Women in the intervention group had lower actual than anticipated levels of fear and anxiety between baseline and two weeks post natal (anxiety: OR -0.72, 95% CI -1.16 to -0.28, P= 0.001); fear (OR -0.62, 95% CI -1.08 to -0.16, p = 0.009) Postnatal response rates were 67% overall at two weeks. The additional cost of the intervention per woman was £4.83 (CI -£257.93 to £267.59). Conclusions: Allocation to two third-trimester group self-hypnosis training sessions did not significantly reduce intra-partum epidural analgesia use or a range of other clinical and psychological variables. The impact of women’s anxiety and fear about childbirth needs further investigation. Trial registration: ISRCTN27575146 http://www.controlled-trials.com/ISRCTN2757514

Establishing a small scale model with MULTIVARIATE and bayesian statistics

One of the primary challenges during process characterization is establishing the suitability of the small scale models used to generate the data. Monte Carlo simulations of small scale data are able to account for increased variability in process parameters seen at large scale. However, this approach requires an accurate estimate of the large-scale variability, which is complicated by the small size of typical large-scale data sets. Bayesian statistics offer an alternate approach in which scale effects are accounted for by directly incorporating scaling offsets into predictive models. In this context, Bayesian methods are advantageous because they explicitly account for uncertainty in datasets, which is essential when attempting to estimate scaling offsets based on the small manufacturing-scale datasets. A CHO cell line known to demonstrate scale differences in lactate production was used as an experimental system, where lab-scale bioreactors typically underestimated the lactate levels observed in large-scale bioreactors. To address this issue, multifactor DOE experiments were run on process conditions known in influence lactate, including glucose, pH, cell generational age, base control and cell bank. Conditions were established for high and low lactate at small scale and a multivariate model of lactate production was established. To address the issue of scale predictability, Monte Carlo simulations were performed using both frequentist and hierarchal Bayesian methods. Both models more accurately described the large-scale lactate levels, and gave a more realistic picture of the robustness of the bioreactor process at scale. Overall the Bayesian model tended to predict a higher percentage of runs that would result in high-lactate and therefore a more accurate picture of large scale. Pilot studies were completed to verify the ability of each model to predict high and low-lactate production at large-scale

A temporal refuge from predation can change the outcome of prey species competition

Funding Information: – AS was supported by The Maxwell Institute Graduate School in Analysis and its Applications, a Centre for Doctoral Training funded by the UK Engineering and Physical Sciences Research Council (grant EP/L016508/01), the Scottish Funding Council, Heriot‐Watt University and the University of Edinburgh. Publisher Copyright: © 2022 The Authors. Oikos published by John Wiley & Sons Ltd on behalf of Nordic Society Oikos.Peer reviewedPublisher PD

Feedback control of lactate using Raman spectroscopy

In fed batch cell culture lactate is produced during the growth phase; its consumption is observed when cells enter the stationary phase. This metabolic shift is desirable and tends to favor optimal process performance and product quality. A CHO cell line known not to demonstrate this metabolic shift and produce high lactate was used as an experimental system. Multifactor DOE experiments were run on process conditions known to influence lactate which included glucose, pH, cell generational age, base control, cell bank and scale-up. Conditions were established for high and low lactate results at bench-top and pilot scale. Multivariate models of lactate production were established. Although multiple factors influenced lactate production it was thought that a flexible manufacturing system could convert a worst-case high-lactate profile into desirable low-lactate profile. Previous work has demonstrated the feasibility of controlling lactate and glucose on-line with Raman spectroscopy. Models were established to quantitate in real-time both glucose and lactate concentrations during the bioreactor process. A feedback loop was developed, in which glucose and lactate concentrations were both monitored and used to control a glucose feed pump. The high-lactate process conditions were run with this two factor feedback control in both bench-top scale and pilot scale reactors. The results demonstrated that a culture could be shifted to lactate consumption converting a high-lactate profile to a low-lactate profile. The system also demonstrated an equivalent or potential increase in over-all titer. Work is continuing to establish this system as a back-up control to prevent high-lactate in future manufacturing

Questioning Favoured Truths of Work and Learning Research

Conference Report – bi-annual Researching Work and Learning international conference.- in Roskilde University, Denmark. I attended the conference. We (my 2 fellow presenters and I) had an hour and a half to present and discuss the paper -- we each took 20 minutes to explain our section. We were followed by an appointed “discussant” and general discussion. The paper is included in the conference CD. The paper was well received and was selected for consideration by the Journal of Workplace Learning – this will give us a chance to further develop ideas and pick up some of the points made in discussion. I also gave a ten minute presentation as part of a panel on a new book based on selected papers given at the previous conference in South Africa. Both presentations are attached. I attended (as a member of the international advisory committee) a planning meeting for the next conference in 2 years time. Bruce Spencer CWCSQuestioning Favoured Truths of Work and Learning Research Peter Sawchuk, Bonnie Slade and Bruce Spencer This paper seeks to open a discussion about some of the assumptions that underpin policy and research on work and learning. Our rationale for the paper is that there exists a set of ideas that are still too often taken for granted. From among this set of ideas we focus on the three key areas: a) human capital and productivity, b) the notion of work experience, and c) skill. Each of these intersecting concepts is informed by specific empirical projects yet in this paper they are undertaken in the first instance as a conceptual problem. Each section of the paper undertakes its exploration on the basis of questions of social justice, empowerment and economic democracy, and raises questions about how framing these concepts as individual traits conceals exclusionary social practices. In terms of human capital and productivity we argue that the contribution of education and training to overall economic development and growth, as well as to an individual's economic future, has been recognized for some time. The idea of human capital in this regard comes from the individualising of the argument: if workers wanted good jobs and avoid unemployment they had to “invest” in their own education and learning (this was no longer primarily a state responsibility). This must be also grasped at the level of the firm where employees can learn and contribute to organizational learning producing collective human capital. The importance of labour productivity in growth, competitiveness and trade is often closely linked here, and yet notions of productivity cannot easily be generalised. In terms of the notion of point (b) ‘work experience’, we argue it to be a central term used to understand access to labour markets. We argue that this term is often seen as an unproblematic for the functioning of labour markets particularly in policy-making research. What are the most relevant ways to critically understand this notion of ‘work experience’? We argue that answers to this question must recognize its construction in relation to global market-driven ideologies, and differential effects (e.g. for immigrants). Our approach highlights work experience as a set of relational practices which mobilize, organize, and concert work across various settings to shape access to the labour market. The notions of skill, de-skilling and up-skilling likewise are more often presumed than they are critically analyzed in much work and learning research. There is a long tradition associated with these questions but still this persists. To what degree is skill presumed to be an individual capacity? Even accepting a social dimension to the notion of skill – is ‘de-skilling’ possible if workers are learning all the time? And finally what is the role of value judgment in assessing instances of ‘de-skilling’ and ‘up-skilling’

Risk factors for human infection with West Nile Virus in Connecticut: a multi-year analysis

<p>Abstract</p> <p>Background</p> <p>The optimal method for early prediction of human West Nile virus (WNV) infection risk remains controversial. We analyzed the predictive utility of risk factor data for human WNV over a six-year period in Connecticut.</p> <p>Results and Discussion</p> <p>Using only environmental variables or animal sentinel data was less predictive than a model that considered all variables. In the final parsimonious model, population density, growing degree-days, temperature, WNV positive mosquitoes, dead birds and WNV positive birds were significant predictors of human infection risk, with an ROC value of 0.75.</p> <p>Conclusion</p> <p>A real-time model using climate, land use, and animal surveillance data to predict WNV risk appears feasible. The dynamic patterns of WNV infection suggest a need to periodically refine such prediction systems.</p> <p>Methods</p> <p>Using multiple logistic regression, the 30-day risk of human WNV infection by town was modeled using environmental variables as well as mosquito and wild bird surveillance.</p