The business of people: the significance of social science over the next decade

Tackling infectious disease, coping with climate change, boosting growth – the major challenges facing our society and economy demand sharp social science. This 2015 pre-election report from the Campaign for Social Science makes urgent recommendations – on research funding, social science capacity and use of expert advice by government – to maximise social science’s contribution through the next Parliament and beyond

Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy

Selective laser sintering (SLS) 3D printing is capable of revolutionising pharmaceutical manufacturing, by producing amorphous solid dispersions in a one-step manufacturing process. Here, 3D-printed formulations loaded with a model BCS class II drug (20% w/w itraconazole) and three grades of hydroxypropyl cellulose (HPC) polymer (-SSL, -SL and -L) were produced using SLS 3D printing. Interestingly, the polymers with higher molecular weights (HPC-L and -SL) were found to undergo a uniform sintering process, attributed to the better powder flow characteristics, compared with the lower molecular weight grade (HPC-SSL). XRPD analyses found that the SLS 3D printing process resulted in amorphous conversion of itraconazole for all three polymers, with HPC-SSL retaining a small amount of crystallinity on the drug product surface. The use of process analytical technologies (PAT), including near infrared (NIR) and Raman spectroscopy, was evaluated, to predict the amorphous content, qualitatively and quantitatively, within itraconazole-loaded formulations. Calibration models were developed using partial least squares (PLS) regression, which successfully predicted amorphous content across the range of 0–20% w/w. The models demonstrated excellent linearity (R^{2} = 0.998 and 0.998) and accuracy (RMSEP = 1.04% and 0.63%) for NIR and Raman spectroscopy models, respectively. Overall, this article demonstrates the feasibility of SLS 3D printing to produce solid dispersions containing a BCS II drug, and the potential for NIR and Raman spectroscopy to quantify amorphous content as a non-destructive quality control measure at the point-of-care

Effect of deletion of the protein kinase PRKD1 on development of the mouse embryonic heart

Congenital heart disease (CHD) is the most common congenital anomaly, with an overall incidence of approximately 1% in the United Kingdom. Exome sequencing in large CHD cohorts has been performed to provide insights into the genetic aetiology of CHD. This includes a study of 1891 probands by our group in collaboration with others, which identified three novel genes—CDK13, PRKD1, and CHD4, in patients with syndromic CHD. PRKD1 encodes a serine/threonine protein kinase, which is important in a variety of fundamental cellular functions. Individuals with a heterozygous mutation in PRKD1 may have facial dysmorphism, ectodermal dysplasia and may have CHDs such as pulmonary stenosis, atrioventricular septal defects, coarctation of the aorta and bicuspid aortic valve. To obtain a greater appreciation for the role that this essential protein kinase plays in cardiogenesis and CHD, we have analysed a Prkd1 transgenic mouse model (Prkd1 em1 ) carrying deletion of exon 2, causing loss of function. High‐resolution episcopic microscopy affords detailed morphological 3D analysis of the developing heart and provides evidence for an essential role of Prkd1 in both normal cardiac development and CHD. We show that homozygous deletion of Prkd1 is associated with complex forms of CHD such as atrioventricular septal defects, and bicuspid aortic and pulmonary valves, and is lethal. Even in heterozygotes, cardiac differences occur. However, given that 97% of Prkd1 heterozygous mice display normal heart development, it is likely that one normal allele is sufficient, with the defects seen most likely to represent sporadic events. Moreover, mRNA and protein expression levels were investigated by RT‐qPCR and western immunoblotting, respectively. A significant reduction in Prkd1 mRNA levels was seen in homozygotes, but not heterozygotes, compared to WT littermates. While a trend towards lower PRKD1 protein expression was seen in the heterozygotes, the difference was only significant in the homozygotes. There was no compensation by the related Prkd2 and Prkd3 at transcript level, as evidenced by RT‐qPCR. Overall, we demonstrate a vital role of Prkd1 in heart development and the aetiology of CHD

Participation as Post-Fordist Politics: Demos, New Labour, and Science Policy

In recent years, British science policy has seen a significant shift ‘from deficit to dialogue’ in conceptualizing the relationship between science and the public. Academics in the interdisciplinary field of Science and Technology Studies (STS) have been influential as advocates of the new public engagement agenda. However, this participatory agenda has deeper roots in the political ideology of the Third Way. A framing of participation as a politics suited to post-Fordist conditions was put forward in the magazine Marxism Today in the late 1980s, developed in the Demos thinktank in the 1990s, and influenced policy of the New Labour government. The encouragement of public participation and deliberation in relation to science and technology has been part of a broader implementation of participatory mechanisms under New Labour. This participatory program has been explicitly oriented toward producing forms of social consciousness and activity seen as essential to a viable knowledge economy and consumer society. STS arguments for public engagement in science have gained influence insofar as they have intersected with the Third Way politics of post-Fordism

Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD

Optical spectroscopic techniques for in-situ characterisation of the milling of concenttrated pigment dispersions

Strathclyde theses - ask staff. Thesis no. : T13449The use of UV-visible, mid infrared, near infrared (NIR) and Raman spectrometries for monitoring the milling of polymer-pigment dispersions was investigated. Experiments showed that both NIR and Raman showed possibility for in-situ monitoring of particle size reduction and were both investigated further. A fundamental investigation of the information content of NIR spectra was completed, showing the influence of particle size on the scattering properties of the pigment dispersions. This was used to rationalise observations made from spectra collected in-situ during particle size reduction experiments on different scales. Cyan, magenta and yellow pigment dispersion NIR spectra, collected in-situ, during milling, showed an increase in baseline offset as pigment size was reduced. Experimentation was performed on < 1 kg scale to develop and assess the technique before applying to larger scale 10 kg and 200 kg milling experiments. Qualitative and quantitative, univariate and multivariate, modelling approaches were explored for monitoring experiments performed on different scales. < 1 kg scale milling experiments showed errors in prediction of between 0.90 -7.96 % for samples at the end point of milling (with particle sizes ranging from 100 to 114 nm). A calibration model derived from < 1 kg experiments was applied to 10 kg milling experiments with an error of prediction of 4.14 % for particles of 110 nm. Qualitative univariate modelling of 200 kg pigment dispersion milling experiments was able to show where faults occurred and where particle size reduction was no longer progressing. The work has demonstrated that in situ NIR measurements could potentially replace the current off-line particle size method. Raman spectroscopy also showed potential for following particle size reduction processes (< 1 kg scale) for cyan and yellow pigment dispersions using a wide area illumination Raman probe. Issues with fluorescence were encountered for magenta pigments and alternatives were explored to remove this.The use of UV-visible, mid infrared, near infrared (NIR) and Raman spectrometries for monitoring the milling of polymer-pigment dispersions was investigated. Experiments showed that both NIR and Raman showed possibility for in-situ monitoring of particle size reduction and were both investigated further. A fundamental investigation of the information content of NIR spectra was completed, showing the influence of particle size on the scattering properties of the pigment dispersions. This was used to rationalise observations made from spectra collected in-situ during particle size reduction experiments on different scales. Cyan, magenta and yellow pigment dispersion NIR spectra, collected in-situ, during milling, showed an increase in baseline offset as pigment size was reduced. Experimentation was performed on < 1 kg scale to develop and assess the technique before applying to larger scale 10 kg and 200 kg milling experiments. Qualitative and quantitative, univariate and multivariate, modelling approaches were explored for monitoring experiments performed on different scales. < 1 kg scale milling experiments showed errors in prediction of between 0.90 -7.96 % for samples at the end point of milling (with particle sizes ranging from 100 to 114 nm). A calibration model derived from < 1 kg experiments was applied to 10 kg milling experiments with an error of prediction of 4.14 % for particles of 110 nm. Qualitative univariate modelling of 200 kg pigment dispersion milling experiments was able to show where faults occurred and where particle size reduction was no longer progressing. The work has demonstrated that in situ NIR measurements could potentially replace the current off-line particle size method. Raman spectroscopy also showed potential for following particle size reduction processes (< 1 kg scale) for cyan and yellow pigment dispersions using a wide area illumination Raman probe. Issues with fluorescence were encountered for magenta pigments and alternatives were explored to remove this