Possible relationship between common genetic variation and white matter development in a pilot study of preterm infants

Background The consequences of preterm birth are a major public health concern with high rates of ensuing multisystem morbidity, and uncertain biological mechanisms. Common genetic variation may mediate vulnerability to the insult of prematurity and provide opportunities to predict and modify risk. Objective To gain novel biological and therapeutic insights from the integrated analysis of magnetic resonance imaging and genetic data, informed by prior knowledge. Methods We apply our previously validated pathway-based statistical method and a novel network-based method to discover sources of common genetic variation associated with imaging features indicative of structural brain damage. Results Lipid pathways were highly ranked by Pathways Sparse Reduced Rank Regression in a model examining the effect of prematurity, and PPAR (peroxisome proliferator-activated receptor) signaling was the highest ranked pathway once degree of prematurity was accounted for. Within the PPAR pathway, five genes were found by Graph Guided Group Lasso to be highly associated with the phenotype: aquaporin 7 (AQP7), malic enzyme 1, NADP(+)-dependent, cytosolic (ME1), perilipin 1 (PLIN1), solute carrier family 27 (fatty acid transporter), member 1 (SLC27A1), and acetyl-CoA acyltransferase 1 (ACAA1). Expression of four of these (ACAA1, AQP7, ME1, and SLC27A1) is controlled by a common transcription factor, early growth response 4 (EGR-4). Conclusions This suggests an important role for lipid pathways in influencing development of white matter in preterm infants, and in particular a significant role for interindividual genetic variation in PPAR signaling

Managing inventory and production capacity in start-up firms

We consider the problem of managing inventory and production capacity in a start-up manufacturing firm with the objective of maximising the probability of the firm surviving as well as the more common objective of maximising profit. Using Markov decision process models, we characterise and compare the form of optimal policies under the two objectives. This analysis shows the importance of coordination in the management of inventory and production capacity. The analysis also reveals that a start-up firm seeking to maximise its chance of survival will often choose to keep production capacity significantly below the profit-maximising level for a considerable time. This insight helps us to explain the seemingly cautious policies adopted by a real start-up manufacturing firm

Warm-Start AlphaZero Self-Play Search Enhancements

Recently, AlphaZero has achieved landmark results in deep reinforcement learning, by providing a single self-play architecture that learned three different games at super human level. AlphaZero is a large and complicated system with many parameters, and success requires much compute power and fine-tuning. Reproducing results in other games is a challenge, and many researchers are looking for ways to improve results while reducing computational demands. AlphaZero's design is purely based on self-play and makes no use of labeled expert data ordomain specific enhancements; it is designed to learn from scratch. We propose a novel approach to deal with this cold-start problem by employing simple search enhancements at the beginning phase of self-play training, namely Rollout, Rapid Action Value Estimate (RAVE) and dynamically weighted combinations of these with the neural network, and Rolling Horizon Evolutionary Algorithms (RHEA). Our experiments indicate that most of these enhancements improve the performance of their baseline player in three different (small) board games, with especially RAVE based variants playing strongly

Preference-Based Monte Carlo Tree Search

Monte Carlo tree search (MCTS) is a popular choice for solving sequential anytime problems. However, it depends on a numeric feedback signal, which can be difficult to define. Real-time MCTS is a variant which may only rarely encounter states with an explicit, extrinsic reward. To deal with such cases, the experimenter has to supply an additional numeric feedback signal in the form of a heuristic, which intrinsically guides the agent. Recent work has shown evidence that in different areas the underlying structure is ordinal and not numerical. Hence erroneous and biased heuristics are inevitable, especially in such domains. In this paper, we propose a MCTS variant which only depends on qualitative feedback, and therefore opens up new applications for MCTS. We also find indications that translating absolute into ordinal feedback may be beneficial. Using a puzzle domain, we show that our preference-based MCTS variant, wich only receives qualitative feedback, is able to reach a performance level comparable to a regular MCTS baseline, which obtains quantitative feedback.Comment: To be publishe

Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling indoor- and outdoor-resting mosquitoes in southern Tanzania.

BACKGROUND\ud \ud Resting mosquitoes can easily be collected using an aspirating device. The most commonly used mechanical aspirator is the CDC Backpack aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has been devised and proved to have comparable performance. The following study evaluates the Prokopack aspirator compared to the CDC backpack aspirator when sampling resting mosquitoes in rural Tanzania.\ud \ud METHODS\ud \ud Mosquitoes were sampled in- and outdoors of 48 typical rural African households using both aspirators. The aspirators were rotated between collectors and households in a randomized, Latin Square design. Outdoor collections were performed using artificial resting places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof and from a drop-net. Data were analysed with generalized linear models.\ud \ud RESULTS\ud \ud The number of mosquitoes collected using the CDC Backpack and the Prokopack aspirator were not significantly different both in- and outdoors (indoors p = 0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The Prokopack was superior for sampling of drop-nets due to its smaller size. The number mosquitoes collected per technician was more consistent when using the Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred using the it over the CDC backpack aspirator as it weighs considerably less, retains its charge for longer and is easier to manoeuvre.\ud \ud CONCLUSIONS\ud \ud The Prokopack proved in the field to be more advantageous than the CDC Backpack aspirator. It can be self assembled using simple, low-cost and easily attainable materials. This device is a useful tool for researchers or vector-control surveillance programs operating in rural Africa, as it is far simpler and quicker than traditional means of sampling resting mosquitoes. Further longitudinal evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray catch for indoor resting catches are recommended

Inventory control for point-of-use locations in hospitals

Most inventory management systems at hospital departments are characterised by lost sales, periodic reviews with short lead times, and limited storage capacity. We develop two types of exact models that deal with all these characteristics. In a capacity model, the service level is maximised subject to a capacity restriction, and in a service model the required capacity is minimised subject to a service level restriction. We also formulate approximation models applicable for any lost-sales inventory system (cost objective, no lead time restrictions etc). For the capacity model, we develop a simple inventory rule to set the reorder levels and order quantities. Numerical results for this inventory rule show an average deviation of 1% from the optimal service levels. We also embed the single-item models in a multi-item system. Furthermore, we compare the performance of fixed order size replenishment policies and (R, s, S) policies

Treatment of primary headache in children: a multicenter hospital-based study in France

The aim of this 6-month, prospective, multicenter study of 398 children and adolescents with primary headaches was to collect data on headache treatment in neuropediatric departments. Treatments were compared before and after consultation. Prior to consultation, the acute treatments that had been prescribed most frequently were paracetamol (82.2% of children) and non-steroidal anti-inflammatory drugs treatment (53.5%); 10.3% had received a prophylactic treatment. No differences in either acute or prophylactic treatment with respect to headache diagnosis were observed. After the neuropediatric consultation, paracetamol was replaced by a non-steroidal anti-inflammatory drug in about three-quarters of cases and by triptan in about one-quarter of cases. The number of children prescribed a prophylactic treatment nearly doubled, whereas there was a 5-fold and 23-fold increase in psychotherapy and relaxation training, respectively, between pre-referral and referral. We conclude that specific treatments were underused for primary headache

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)

Neurotized Free Muscle Flaps can Produce MRI Changes Mimicking Tumour Recurrence

Soft tissue sarcomas are investigated by magnetic resonance imaging (MRI) both for initial staging and follow-up. We describe the presence of increased signal on T2-weighted images caused by a neurotized muscle flap following reconstructive surgery. This raised concern about possible sarcoma recurrence that was not clinically evident. On post-operative imaging of sarcomas the presence of recurrent tumour is indicated by a mass and high signal intensity on T2-weighted images. However, high signal changes in skeletal muscle on T2-weighted images are not specific. In this case, the free functioning muscle transfer with neurotization of the flap mimicked recurrence on MR scan. High signal intensity on T2-weighted images in muscle is an indication of either a physiological change or a pathological condition and must be taken in context of the clinical picture