Quantifying the macroeconomic cost of night-time bathroom visits: an application to the UK

Little is known on the impact that nocturia (the need to wake up at night to urinate) has on a nation’s economy. While there are many individual factors associated with inadequate sleep (e.g. bad sleep hygiene, chronic sleep disorders such as insomnia or sleep apnea), frequently having to wake up at night to urinate fragments sleep, with negative consequences on an individual’s health and well-being as well as daytime functioning. Using a large-scale UK workforce data, we estimate the prevalence of nocturia in the working population and quantify the lost worker productivity caused by nocturia, measured by absenteeism and presenteeism. This enters our multi-country general equilibrium model, which we calibrate to the UK economy, to estimate the annual macroeconomic cost of nocturia. We find the annual cost of clinically significant nocturia (waking up at least twice to urinate) is around £5.4 billion, or equivalently £1996 per worker with nocturia. This cost estimate is larger than previous estimates on the productivity effects of nocturia using cost-of-illness (COI) methods, suggesting the importance of taking into account general equilibrium effects when assessing the economic burden of health conditions

Wafer-Scale Assembly of Semiconductor Nanowire Arrays by Contact Printing

Controlled and uniform assembly of "bottom-up" nanowire (NW) materials with high scalability has been one of the significant bottleneck challenges facing the potential integration of nanowires for both nano and macro electronic circuit applications. Many efforts have focused on tackling this challenge, and while significant progress has been made, still most presented approaches lack either the desired controllability in the positioning of nanowires or the needed uniformity over large scales. Here, we demonstrate wafer-scale assembly of highly ordered, dense, and regular arrays of NWs with high uniformity and reproducibility through a simple contact printing process. We demonstrate contact printing as a versatile strategy for direct transfer and controlled positioning of various NW materials into complex structural configurations on substrates. The assembled NW pitch is shown to be readily modulated through the surface chemical treatment of the receiver substrate, with the highest density approaching ~8 NW/um, ~95% directional alignment and wafer-scale uniformity. Furthermore, we demonstrate that our printing approach enables large-scale integration of NW arrays for various device structures on both Si and plastic substrates, with a controlled semiconductor channel width, and therefore ON current, ranging from a single NW (~10 nm) and up to ~250 um, consisting of a parallel array of over 1,250 NWs.Comment: 14 pages,4 figure

Inevitable Evolutionary Temporal Elements in Neural Processing: A Study Based on Evolutionary Simulations

Recent studies have suggested that some neural computational mechanisms are based on the fine temporal structure of spiking activity. However, less effort has been devoted to investigating the evolutionary aspects of such mechanisms. In this paper we explore the issue of temporal neural computation from an evolutionary point of view, using a genetic simulation of the evolutionary development of neural systems. We evolve neural systems in an environment with selective pressure based on mate finding, and examine the temporal aspects of the evolved systems. In repeating evolutionary sessions, there was a significant increase during evolution in the mutual information between the evolved agent's temporal neural representation and the external environment. In ten different simulated evolutionary sessions, there was an increased effect of time -related neural ablations on the agents' fitness. These results suggest that in some fitness landscapes the emergence of temporal elements in neural computation is almost inevitable. Future research using similar evolutionary simulations may shed new light on various biological mechanisms

Molecular characterization of the intact mouse muscle spindle using a multi-omics approach

The proprioceptive system is essential for the control of coordinated movement, posture and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle isolated from the murine deep masseter muscle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development. Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy

Acknowledgements We would like to thank Dr. Nicholas Senn for conducting data auditing, Dr. Matthew Clemence (Philips Healthcare Clinical Science, UK) for clinical scientist support, Dr. Tim Smith for biologist support, Mr. Gordon Buchan for technician support, Ms Bolanle Brikinns for patient recruitment support, Ms Dawn Younie for logistic support, Prof. Andrew M. Blamire for advice on MRS. We would also like to thank Mr Roger Bourne and Ms Mairi Fuller for providing access to the patients. Data availability Data supporting this publication are stored at Institute of Medical Sciences and available upon request. Funding information This project was funded by Friends of Aberdeen and North Centre for Haematology, Oncology and Radiotherapy (ANCHOR) (RS2015 004). Sai Man Cheung’s PhD study was jointly supported by Elphinstone scholarship, Roland Sutton Academic Trust and John Mallard scholarship.Peer reviewedPublisher PD

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation