Monthly GDP Estimates for Inter-War Britain

We derive monthly and quarterly series of UK GDP for the inter-war period from a set of monthly indicators that were constructed by The Economist at the time. The monthly information is complemented with data for quarterly industrial production, allowing us to employ mixed-frequency methods to produce monthly estimates of GDP and of industrial production. We proceed to illustrate how the new data compare with existing high frequency data and how they can be used to contribute to our understanding of the economic history of the UK in the inter-war period and to draw comparisons between recession profiles in the inter-war and the post-war period

Motion-corrected multiparametric renal arterial spin labelling at 3T: Reproducibility and effect of vasodilator challenge

Objectives We investigated the feasibility and reproducibility of free-breathing motion-corrected multiple inversion time (multi-TI) pulsed renal arterial spin labelling (PASL), with general kinetic model parametric mapping, to simultaneously quantify renal perfusion (RBF), bolus arrival time (BAT) and tissue T1. Methods In a study approved by the Health Research Authority, 12 healthy volunteers (mean age, 27.6 ± 18.5 years; 5 male) gave informed consent for renal imaging at 3 T using multi-TI ASL and conventional single-TI ASL. Glyceryl trinitrate (GTN) was used as a vasodilator challenge in six subjects. Flow-sensitive alternating inversion recovery (FAIR) preparation was used with background suppression and 3D-GRASE (gradient and spin echo) read-out, and images were motion-corrected. Parametric maps of RBF, BAT and T1 were derived for both kidneys. Agreement was assessed using Pearson correlation and Bland-Altman plots. Results Inter-study correlation of whole-kidney RBF was good for both single-TI (r2 = 0.90), and multi-TI ASL (r2 = 0.92). Single-TI ASL gave a higher estimate of whole-kidney RBF compared to multi-TI ASL (mean bias, 29.3 ml/min/100 g; p <0.001). Using multi-TI ASL, the median T1 of renal cortex was shorter than that of medulla (799.6 ms vs 807.1 ms, p = 0.01), and mean whole-kidney BAT was 269.7 ± 56.5 ms. GTN had an effect on systolic blood pressure (p < 0.05) but the change in RBF was not significant. Conclusions Free-breathing multi-TI renal ASL is feasible and reproducible at 3 T, providing simultaneous measurement of renal perfusion, haemodynamic parameters and tissue characteristics at baseline and during pharmacological challenge

Randomly hyperbranched polymers

We describe a model for the structures of randomly hyperbranched polymers in solution, and find a logarithmic growth of radius with polymer mass. We include segmental overcrowding, which puts an upper limit on the density. The model is tested against simulations, against data on amylopectin, a major component of starch, on glycogen, and on polyglycerols. For samples of synthetic polyglycerol and glycogen, our model holds well for all the available data. The model reveals higher-level scaling structure in glycogen, related to the beta particles seen in electron microscopy

Applying the ‘least dangerous assumption’ in regard to behaviour policies and children with special needs

Children with special needs and disabilities (SEND) in mainstream schools have a wide range of complex conditions rendering it impossible for teachers to fully understand all the complexities of their needs. Difficulties with understanding and self-control lead to much of the behaviour that is considered unacceptable within schools and that can ultimately lead to the large numbers of children with SEND who are excluded. Schools often wish to provide a behaviour policy where everyone is treated equally despite people’s needs and abilities being different. Government guidance in relation to behaviour policies is that they should comprise a mixture of sanctions and rewards, but this behaviourist view leads to a lack of equity of response to behaviour, again feeding into disproportionate numbers of children with SEND being excluded. The move from sanctions and rewards to the operation of a relationships policy where students’ actions yield consequences, within a humanist ethos of understanding, would far more effectively support all children to learn to moderate and control their behaviour and would allow staff to apply the ‘least dangerous assumption’ when dealing with challenging students

Frontotemporal dementia: insights into the biological underpinnings of disease through gene co-expression network analysis

BACKGROUND: In frontotemporal dementia (FTD) there is a critical lack in the understanding of biological and molecular mechanisms involved in disease pathogenesis. The heterogeneous genetic features associated with FTD suggest that multiple disease-mechanisms are likely to contribute to the development of this neurodegenerative condition. We here present a systems biology approach with the scope of i) shedding light on the biological processes potentially implicated in the pathogenesis of FTD and ii) identifying novel potential risk factors for FTD. We performed a gene co-expression network analysis of microarray expression data from 101 individuals without neurodegenerative diseases to explore regional-specific co-expression patterns in the frontal and temporal cortices for 12 genes (MAPT, GRN, CHMP2B, CTSC, HLA-DRA, TMEM106B, C9orf72, VCP, UBQLN2, OPTN, TARDBP and FUS) associated with FTD and we then carried out gene set enrichment and pathway analyses, and investigated known protein-protein interactors (PPIs) of FTD-genes products. RESULTS: Gene co-expression networks revealed that several FTD-genes (such as MAPT and GRN, CTSC and HLA-DRA, TMEM106B, and C9orf72, VCP, UBQLN2 and OPTN) were clustering in modules of relevance in the frontal and temporal cortices. Functional annotation and pathway analyses of such modules indicated enrichment for: i) DNA metabolism, i.e. transcription regulation, DNA protection and chromatin remodelling (MAPT and GRN modules); ii) immune and lysosomal processes (CTSC and HLA-DRA modules), and; iii) protein meta/catabolism (C9orf72, VCP, UBQLN2 and OPTN, and TMEM106B modules). PPI analysis supported the results of the functional annotation and pathway analyses. CONCLUSIONS: This work further characterizes known FTD-genes and elaborates on their biological relevance to disease: not only do we indicate likely impacted regional-specific biological processes driven by FTD-genes containing modules, but also do we suggest novel potential risk factors among the FTD-genes interactors as targets for further mechanistic characterization in hypothesis driven cell biology work

Iron Age and Anglo-Saxon genomes from East England reveal British migration history

British population history has been shaped by a series of immigrations, including the early Anglo-Saxon migrations after 400 CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences from 10 individuals excavated close to Cambridge in the East of England, ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. We gain further insight with a new method, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain