Deciphering Elapsed Time and Predicting Action Timing from Neuronal Population Signals

The proper timing of actions is necessary for the survival of animals, whether in hunting prey or escaping predators. Researchers in the field of neuroscience have begun to explore neuronal signals correlated to behavioral interval timing. Here, we attempt to decode the lapse of time from neuronal population signals recorded from the frontal cortex of monkeys performing a multiple-interval timing task. We designed a Bayesian algorithm that deciphers temporal information hidden in noisy signals dispersed within the activity of individual neurons recorded from monkeys trained to determine the passage of time before initiating an action. With this decoder, we succeeded in estimating the elapsed time with a precision of approximately 1 s throughout the relevant behavioral period from firing rates of 25 neurons in the pre-supplementary motor area. Further, an extended algorithm makes it possible to determine the total length of the time-interval required to wait in each trial. This enables observers to predict the moment at which the subject will take action from the neuronal activity in the brain. A separate population analysis reveals that the neuronal ensemble represents the lapse of time in a manner scaled relative to the scheduled interval, rather than representing it as the real physical time

A TIM-3/Gal-9 Autocrine Stimulatory Loop Drives Self-Renewal of Human Myeloid Leukemia Stem Cells and Leukemic Progression

SummarySignaling mechanisms underlying self-renewal of leukemic stem cells (LSCs) are poorly understood, and identifying pathways specifically active in LSCs could provide opportunities for therapeutic intervention. T-cell immunoglobin mucin-3 (TIM-3) is expressed on the surface of LSCs in many types of human acute myeloid leukemia (AML), but not on hematopoietic stem cells (HSCs). Here, we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for LSC self-renewal and development of human AML. Serum Gal-9 levels were significantly elevated in AML patients and in mice xenografted with primary human AML samples, and neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML. Gal-9-mediated stimulation of TIM-3 co-activated NF-κB and β-catenin signaling, pathways known to promote LSC self-renewal. These changes were further associated with leukemic transformation of a variety of pre-leukemic disorders and together highlight that targeting the TIM-3/Gal-9 autocrine loop could be a useful strategy for treating myeloid leukemias

Association between contrast extravasation on computed tomography scans and pseudoaneurysm formation in pediatric blunt splenic and hepatic injury: A multi-institutional observational study

PURPOSE: We aimed to examine the association between contrast extravasation (CE) on initial computed tomography (CT) scan and pseudoaneurysm (PSA) development in pediatric blunt splenic and/or liver injury. METHODS: We conducted a multi-institutional retrospective study in cases of blunt splenic and/or hepatic injury who underwent an initial attempt of nonoperative management. A logistic regression model was used to compare PSA formation and CE on initial CT scan, and the area under the receiver operating characteristic curve (AUC) with and without CE was used to assess the predictive performance of CE for PSA formation. RESULTS: Of 236 cases enrolled from 10 institutions, PSA formation was observed in 17 (7.2%). Multivariate analysis showed a significant association between CE on initial CT scan and increased incidence of PSA formation (odds ratio, 4.96; 95% confidence interval, 1.37-18.0). There was no statistically significant association between the grade of injury and PSA formation. The AUC improved from 0.75 (0.64-0.87) to 0.80 (0.70-0.91) with CE. CONCLUSION: Active CE on initial CT scan was an independent predictor of PSA formation. Selective use of follow-up CT in children who showed CE on initial CT may provide early identification of PSA formation, regardless of injury grade. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III

Visualizing Nanoscale Distribution of Corrosion Cells by Open-Loop Electric Potential Microscopy

Corrosion is a traditional problem but still one of the most serious problems in industry. To reduce the huge economic loss caused by corrosion, tremendous effort has been made to understand, predict and prevent it. Corrosion phenomena are generally explained by the formation of corrosion cells at a metal-electrolyte interface. However, experimental verification of their nanoscale distribution has been a major challenge owing to the lack of a method able to visualize the local potential distribution in an electrolytic solution. In this study, we have investigated the nanoscale corrosion behavior of Cu fine wires and a duplex stainless steel by in situ imaging of local corrosion cells by open-loop electric potential microscopy (OL-EPM). For both materials, potential images obtained by OL-EPM show nanoscale contrasts, where areas of higher and lower potential correspond to anodic areas (i.e., corrosion sites) and cathodic areas, respectively. This imaging capability allows us to investigate the real-time transition of local corrosion sites even when surface structures show little change. This is particularly useful for investigating reactions under surface oxide layers or highly corrosion-resistant materials as demonstrated here. The proposed technique should be applicable to the study of other redox reactions on a battery electrode or a catalytic material. The results presented here open up such future applications of OL-EPM in nanoscale electrochemistry. © 2016 American Chemical Society.Embargo Period 12 month

Development of D-to-D-to-P telemedicine at a remote island hospital using smart glasses

Background: Medical resources on remote islands are limited, which makes it difficult for patients to receive specialized medical care.Purpose: This study aimed to develop and evaluate a method to perform doctor-to-doctor-to-patient (D-to-D-to-P) telemedicine.Methods: The-D-to-D-to-P telemedicine was implemented to provide specialized medical support from a neurologist at Nagasaki University Hospital to a rural physician wearing camera-equipped smart glasses at Goto Chuoh Hospital on a remote island, which was called a virtual neurological outpatient (VNO). For the first six months, the rural physician independently saw patients with Parkinson’s disease (PD), and then for the next six months, VNO was implemented. Comparisons were made before and after the implementation of the VNO. Next, by adding a 4 K overhead camera, in-person examinations of a single outpatient were compared between the rural physician with VNO and another neurologist unrelated to the VNO.Results: The clinical efficacy of VNO was not superior to no VNO, but had a learning effect on rural physicians and was satisfactory for patients. By adding a 4 K overhead camera to the VNO, the accuracy of the in-person examination by the rural physician was shown to be equivalent to that of an in-person neurologist.Conclusion: VNO using smart glasses could be applied for D-to-D-to-P telemedicine in neurology. However, to promote telemedicine on remote islands, it will be necessary to improve the system to make it more accessible to rural physicians

Mutant analyses reveal different functions of fgfr1 in medaka and zebrafish despite conserved ligand–receptor relationships

AbstractMedaka (Oryzias latipes) is a small freshwater teleost that provides an excellent developmental genetic model complementary to zebrafish. Our recent mutagenesis screening using medaka identified headfish (hdf) which is characterized by the absence of trunk and tail structures with nearly normal head including the midbrain–hindbrain boundary (MHB). Positional-candidate cloning revealed that the hdf mutation causes a functionally null form of Fgfr1. The fgfr1hdf is thus the first fgf receptor mutant in fish. Although FGF signaling has been implicated in mesoderm induction, mesoderm is induced normally in the fgfr1hdf mutant, but subsequently, mutant embryos fail to maintain the mesoderm, leading to defects in mesoderm derivatives, especially in trunk and tail. Furthermore, we found that morpholino knockdown of medaka fgf8 resulted in a phenotype identical to the fgfr1hdf mutant, suggesting that like its mouse counterpart, Fgf8 is a major ligand for Fgfr1 in medaka early embryogenesis. Intriguingly, Fgf8 and Fgfr1 in zebrafish are also suggested to form a major ligand–receptor pair, but their function is much diverged, as the zebrafish fgfr1 morphant and zebrafish fgf8 mutant acerebellar (ace) only fail to develop the MHB, but develop nearly unaffected trunk and tail. These results provide evidence that teleost fish have evolved divergent functions of Fgf8–Fgfr1 while maintaining the ligand–receptor relationships. Comparative analysis using different fish is thus invaluable for shedding light on evolutionary diversification of gene function

Transition of Anesthesia Management and Anesthetics Used for 50 Years Since the Establishment of Anesthesiology Department in Hiroshima University

広島大学麻酔蘇生学教室は1967年1月に盛生倫夫が初代教授に就任し開講した。開講50周年を機に，麻酔科開設以来の麻酔管理に用いた麻酔薬の変遷を辿った。開講当初から１９８５年までは亜酸化窒素とハロタンを中心とした吸入麻酔薬の時代，1990年から2005年はエンフルラン，イソフルラン，セボフルランなどの吸入麻酔薬とフェンタニルの併用の時で，2010年からはプロポフォールとレミフェンタニルの全静脈麻酔あるいはセボフルランあるいはデスフルランとレミフェンタニル併用の時代であった。開講から1980年頃まではスキサメトニウムを主に使ったが，それ以降は非脱分極性筋弛緩薬であるパンクロニウムへ，そしてベクロニウムへ推移し，現在はロクロニウムが主流となっている。使用麻酔薬の変遷は麻酔薬の科学的な評価とそれらを使用する麻酔科医の考え方を反映していた。Department of Anesthesiology and Critical Care, Hiroshima University, started in January 1967 when Dr. Michio Morio became the first professor.　With the 50th anniversary of the establishment of the department, the transition of the anesthetics used in our long history of anesthesia care was investigated since the beginning of the department. Inhalation anesthetics was mainly used in combination with nitrous oxide and halothane from the beginning to 1985. Inhalation anesthetics such as enflurane, isoflurane, sevoflurane and intravenous fentanyl were used from 1990 to 2005, and the total intravenous anesthesia by using propofol and remifentanil was introduced and used currently. Sevoflurane or desflurane combined with remifentanil was also a mainstream since 2010.　From the beginning to 1980, suxamethonium was mainly used for muscle relaxation, followed by pancuronium thereafter and shifted to vecuronium and to rocuronium. The transition of anesthetics applied for clinical anesthesia in our department seemed to be reflecting the selection based on scientific validity

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements