Current approaches used in epidemiologic studies to examine short-term multipollutant air pollution exposures

Air pollution epidemiology traditionally focuses on the relationship between individual air pollutants and health outcomes (e.g., mortality). To account for potential copollutant confounding, individual pollutant associations are often estimated by adjusting or controlling for other pollutants in the mixture. Recently, the need to characterize the relationship between health outcomes and the larger multipollutant mixture has been emphasized in an attempt to better protect public health and inform more sustainable air quality management decisions

A randomised feasibility study of serial magnetic resonance imaging to reduce treatment times in Charcot neuroarthropathy in people with diabetes (CADOM): A protocol

Background Charcot neuroarthropathy is a complication of peripheral neuropathy associated with diabetes which most frequently affects the lower limb. It can cause fractures and dislocations within the foot, which may progress to deformity and ulceration. Recommended treatment is immobilisation and offloading, with a below knee non-removable cast or boot. Duration of treatment varies from six months to more than one year. Small observational studies suggest that repeated assessment with Magnetic Resonance Imaging improves decision making about when to stop treatment, but this has not been tested in clinical trials. This study aims to explore the feasibility of using serial Magnetic Resonance Imaging without contrast in the monitoring of Charcot neuroarthropathy to reduce duration of immobilisation of the foot. A nested qualitative study aims to explore participants’ lived experience of Charcot neuroarthropathy and of taking part in the feasibility study. Methods We will undertake a two arm, open study, and randomise 60 people with a suspected or confirmed diagnosis of Charcot neuroarthropathy from five NHS, secondary care multidisciplinary Diabetic Foot Clinics across England. Participants will be randomised 1:1 to receive Magnetic Resonance Imaging at baseline and remission up to 12 months, with repeated foot temperature measurements and x-rays (standard care plus), or standard care plus with additional three-monthly Magnetic Resonance Imaging until remission up to 12 months (intervention). Time to confirmed remission of Charcot neuroarthropathy with off-loading treatment (days) and its variance will be used to inform sample size in a full-scale trial. We will look for opportunities to improve the protocols for monitoring techniques and the clinical, patient centred, and health economic measures used in a future study. For the nested qualitative study, we will invite a purposive sample of 10-14 people able to offer maximally varying experiences from the feasibility study to take part in semi-structured interviews to be analysed using thematic analysis. Discussion The study will inform the decision whether to proceed to a full-scale trial. It will also allow deeper understanding of the lived experience of Charcot neuroarthropathy, and factors that contribute to engagement in management and contribute to the development of more effective patient centred strategies. Trial registration ISRCTN, ISRCTN, 74101606. Registered on 6 November 2017, http://www.isrctn.com/ISRCTN74101606?q=CADom&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-searc

p75 neurotrophin receptor regulates energy balance in obesity

Obesity and metabolic syndrome reflect the dysregulation of molecular pathways that control energy homeostasis. Here, we show that the p75 neurotrophin receptor (p75NTR) controls energy expenditure in obese mice on a high-fat diet (HFD). Despite no changes in food intake, p75NTR-null mice were protected from HFD-induced obesity and remained lean as a result of increased energy expenditure without developing insulin resistance or liver steatosis. p75NTR directly interacts with the catalytic subunit of protein kinase A (PKA) and regulates cAMP signaling in adipocytes, leading to decreased lipolysis and thermogenesis. Adipocyte-specific depletion of p75NTR or transplantation of p75NTR-null white adipose tissue (WAT) into wild-type mice fed a HFD protected against weight gain and insulin resistance. Our results reveal that signaling from p75NTR to cAMP/PKA regulates energy balance and suggest that non-CNS neurotrophin receptor signaling could be a target for treating obesity and the metabolic syndrome

BER-Adaptive RMLSA Algorithm for Wide-Area Flexible Optical Networks

Wide-area optical networks face significant transmission challenges due to the relentless growth of bandwidth demands experienced nowadays. Network operators must consider the relationship between modulation format and maximum reach for each connection request due to the accumulation of physical layer impairments in optical fiber links, to guarantee a minimum quality of service (QoS) and quality of transmission (QoT) to all connection requests. In this work, we present a BER-adaptive solution to solve the routing, modulation format, and spectrum assignment (RMLSA) problem for wide-area elastic optical networks. Our main goal is to maximize successful connection requests in wide-area networks while choosing modulation formats with the highest efficiency possible. Consequently, our technique uses an adaptive bit-error-rate (BER) threshold to achieve communication with the best QoT in the most efficient manner, using the strictest BER value and the modulation format with the smallest bandwidth possible. Additionally, the proposed algorithm relies on 3R regeneration devices to enable long-distances communications if transparent communication cannot be achieved. We assessed our method through simulations for various network conditions, such as the number of regenerators per node, traffic load per user, and BER threshold values. In a scenario without regenerators, the BER-Adaptive algorithm performs similarly to the most relaxed fixed BER threshold studied in blocking probability. However, it ensures a higher QoT to most of the connection requests. The proposed algorithm thrives with the use of regenerators, showing the best performance among the studied solutions, enabling long-distance communications with a high QoT and low blocking probability

Investigating rate increase in aerospace factory by simulation of material flow operations

The main challenge aerospace industries are facing in recent times has been triggered by the remarkable increase in commercial aircraft demand. To address this challenge, aircraft manufacturers need to explore ways to increase capacity and workflow through process optimisation and automation. This study focusses on the optimisation of component flow and inventory during the assembly of the A320 Family wings’ at Airbus (Broughton, UK) plant through Discrete Event Simulation (DES). This research measured the likely impact of future changes in the wing assembly process, using simulation by: mapping of component flow from delivery to the point of use, simulation of current logistics scenario (AS-IS), simulation of future logistics scenarios (TO-BE) that include proposed changes for optimising flow and managing capacity surge, and testing and validation of mapping and simulation. The developed DES model demonstrated the impact of changes planned to be implemented by showing a considerable increase in production capacity growth, by achieving a target of 50% increase of aircraft rate/month within one year. It also highlighted the main problems causing blockages and other non-value activities in the process

Temporal perception deficits in schizophrenia: integration is the problem, not deployment of attentions

Patients with schizophrenia are known to have impairments in sensory processing. In order to understand the specific temporal perception deficits of schizophrenia, we investigated and determined to what extent impairments in temporal integration can be dissociated from attention deployment using Attentional Blink (AB). Our findings showed that there was no evident deficit in the deployment of attention in patients with schizophrenia. However, patients showed an increased temporal integration deficit within a hundred-millisecond timescale. The degree of such integration dysfunction was correlated with the clinical manifestations of schizophrenia. There was no difference between individuals with/without schizotypal personality disorder in temporal integration. Differently from previous studies using the AB, we did not find a significant impairment in deployment of attention in schizophrenia. Instead, we used both theoretical and empirical approaches to show that previous findings (using the suppression ratio to correct for the baseline difference) produced a systematic exaggeration of the attention deficits. Instead, we modulated the perceptual difficulty of the task to bring the baseline levels of target detection between the groups into closer alignment. We found that the integration dysfunction rather than deployment of attention is clinically relevant, and thus should be an additional focus of research in schizophrenia

Evidence of Critical Behavior in the Disassembly of Nuclei with A ~ 36

A wide variety of observables indicate that maximal fluctuations in the disassembly of hot nuclei with A ~ 36 occur at an excitation energy of 5.6 +- 0.5 MeV/u and temperature of 8.3 +- 0.5 MeV. Associated with this point of maximal fluctuations are a number of quantitative indicators of apparent critical behavior. The associated caloric curve does not appear to show a flattening such as that seen for heavier systems. This suggests that, in contrast to similar signals seen for liquid-gas transitions in heavier nuclei, the observed behavior in these very light nuclei is associated with a transition much closer to the critical point.Comment: v2: Major changes, new model calculations, new figure

Critical Behavior in Light Nuclear Systems: Experimental Aspects

An extensive experimental survey of the features of the disassembly of a small quasi-projectile system with $A \sim$ 36, produced in the reactions of 47 MeV/nucleon $^{40}$Ar + $^{27}$Al, $^{48}$Ti and $^{58}$Ni, has been carried out. Nuclei in the excitation energy range of 1-9 MeV/u have been investigated employing a new method to reconstruct the quasi-projectile source. At an excitation energy $\sim$ 5.6 MeV/nucleon many observables indicate the presence of maximal fluctuations in the de-excitation processes. The fragment topological structure shows that the rank sorted fragments obey Zipf's law at the point of largest fluctuations providing another indication of a liquid gas phase transition. The caloric curve for this system shows a monotonic increase of temperature with excitation energy and no apparent plateau. The temperature at the point of maximal fluctuations is $8.3 \pm 0.5$ MeV. Taking this temperature as the critical temperature and employing the caloric curve information we have extracted the critical exponents $\beta$, $\gamma$ and $\sigma$ from the data. Their values are also consistent with the values of the universality class of the liquid gas phase transition. Taken together, this body of evidence strongly suggests a phase change in an equilibrated mesoscopic system at, or extremely close to, the critical point.Comment: Physical Review C, in press; some discussions about the validity of excitation energy in peripheral collisions have been added; 24 pages and 32 figures; longer abstract in the preprin