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Objective: To investigate the clinical outcome, ECG characteristics, and optimal treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), a malignant and rare ventricular tachycardia. Patients and methods: Questionnaire responses and ECGs [...]

Objectives: To investigate the relation between coronary flow reserve (CFR), coronary zero flow pressure (Pzf), and residual myocardial viability in patients with acute myocardial infarction. Designs: Prospective study. Setting: Primary [...]

Objective: To determine whether the early assessment of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE) can predict myocardial viability after revascularisation in patients with acute myocardial infarction. [...]

Despite similar traditional risk factors, morbidity and mortality rates from coronary heart disease in western and non-western cohorts remain substantially different. Careful study of such cohorts may help identify novel [...]

The rise of quantum information science has provided new perspectives on quantum mechanics, as well as a common language for quantum engineering. The focus on platforms for the manipulation and processing of quantum information bridges between different research areas in physics as well as other disciplines. Such a crossover between borders is well embodied by the development of hybrid quantum systems, where heterogeneous physical systems are combined to leverage their individual strengths for the implementation of novel functionalities. In the microwave domain, the hybridization of various quantum degrees of freedom has been tremendously helped by superconducting quantum circuits, owing to their large zero-point field fluctuations, small dissipation, strong nonlinearity and design flexibility. These efforts take place by expanding the framework of circuit quantum electrodynamics. Here, we review recent research on the creation of hybrid quantum systems based on circuit quantum electrodynamics, encompassing mechanical oscillators, quantum acoustodynamics with surface acoustic waves, quantum magnonics and coupling between superconducting circuits and ensembles or single spins.

A gamma‐ray glow, a minute‐lasting burst of high‐energy photons from a thundercloud, was detected by ground‐based apparatus at Kanazawa University, Japan, in a winter thunderstorm on 18 December 2018. The gamma‐ray glow was quenched by a lightning flash within a brief time window of 40 ms. The lightning flash produced several low‐frequency (LF) E‐change pulses that were temporally coincident with the termination of the gamma‐ray glow, and that were located within 0.5 km from the observation site by the Fast Antenna Lightning Mapping Array. The LF pulses had the same polarity as a positive cloud‐to‐ground current and a normal‐polarity in‐cloud current. Since this polarity is against the upward electric field for producing the gamma‐ray glow (accelerating electrons to the ground), we infer that the glow was terminated by a normal‐polarity in‐cloud discharge activity between a middle negative layer and an upper positive layer. Strong electric fields inside thunderclouds may accelerate electrons to relativistic energy, and cause a burst of high‐energy photons called gamma‐ray glow. Gamma‐ray glows are sometimes terminated with a lightning flash as it discharges electric fields responsible for electron acceleration. In this study, we observed the termination of a gamma‐ray glow with a detailed lightning mapping observation in the radio‐frequency band. An in‐cloud lightning flash between two charge layers inside a thundercloud reduced an electric field that accelerated electrons. Radio‐frequency observations of glow termination are a powerful tool to investigate the charge structure associated with electron acceleration. A gamma‐ray glow was terminated by a lightning flash within a brief time window of 40 msPositive‐polarity low‐frequency pulses were located within 0.5 km of the detection siteThe glow was ceased by a normal‐polarity in‐cloud discharge activity between a middle negative layer and an upper positive layer A gamma‐ray glow was terminated by a lightning flash within a brief time window of 40 ms Positive‐polarity low‐frequency pulses were located within 0.5 km of the detection site The glow was ceased by a normal‐polarity in‐cloud discharge activity between a middle negative layer and an upper positive layer

Gamma‐ray glows are observational evidence of relativistic electron acceleration due to the electric field in thunderclouds. However, it is yet to be understood whether such relativistic electrons contribute to the initiation of lightning discharges. To tackle this question, we started the citizen science “Thundercloud Project,” where we map radiation measurements of glows from winter thunderclouds along Japan's sea coast area. We developed and deployed 58 compact gamma‐ray monitors at the end of 2021. On 30 December 2021, five monitors simultaneously detected a glow with its radiation distribution horizontally extending for 2 km. The glow terminated coinciding with a lightning flash at 04:08:34 JST, which was recorded by the two radio‐band lightning mapping systems, FALMA and DALMA. The initial discharges during the preliminary breakdown started above the glow, that is, in vicinity of the electron acceleration site. This result provides one example of possible connections between electron acceleration and lightning initiation. Thunderstorms are natural particle accelerators. The strong electric field inside thunderclouds accelerates relativistic electrons, which emit gamma rays via interaction with the atmosphere. High‐energy photons generated in this process have been observed as radiation enhancements called gamma‐ray glows. Winter thunderclouds along the sea of Japan are an ideal target for monitoring glows because their altitudes are usually sufficiently low for the generated gamma‐ray photons to reach the ground. We started a new citizen science “Thundercloud Project” in this area, where we distributed radiation detectors to citizen supporters to observe glows and to reveal their relationship with the aerological condition and lightning discharges. On 30 December 2021, five of those sensors detected a glow from a single thundercloud. Two of them recorded a sudden termination of the glow coinciding with a lightning flash, which was monitored by our two radio mapping systems of FALMA and DALMA. The initial discharges of the flash started at a location about 1.6 km above the glow region with an unusually fast downward progression. This paper is the first report of our citizen science project. We discuss the possibility that accelerated electrons contribute to the initiation of lightning discharges. We started the citizen science “Thundercloud Project,” a multi‐point observation campaign of gamma‐ray glows from thunderstormsOn 30 December 2021, five radiation monitors detected a 2‐km‐long size gamma‐ray glow, which suddenly terminated with a lightning flashTwo radio mapping systems of lightning identified the initiation of the discharges, which started at a location above the glow region We started the citizen science “Thundercloud Project,” a multi‐point observation campaign of gamma‐ray glows from thunderstorms On 30 December 2021, five radiation monitors detected a 2‐km‐long size gamma‐ray glow, which suddenly terminated with a lightning flash Two radio mapping systems of lightning identified the initiation of the discharges, which started at a location above the glow region

An on‐ground observation program for high‐energy atmospheric phenomena in winter thunderstorms along the Japan Sea has been performed via measurements of gamma ray radiation, atmospheric electric field, and low‐frequency radio band. On 11 February 2017, the radiation detectors recorded gamma ray emission lasting for 75 s, and then abruptly terminated with a nearby lightning discharge. The gamma ray spectrum extended up to 20 MeV and was reproduced by a cutoff power law model with a photon index of 1.36−0.04+0.03, being consistent with Bremsstrahlung radiation from a thundercloud (known as a gamma‐ray glow or a thunderstorm ground enhancement). The low‐frequency radio monitors, installed ∼50 km away from the gamma ray observation site recorded leader development of an intracloud/intercloud discharge spreading over ∼60 km area with a ∼300‐ms duration. The timing of the gamma ray termination coincided with the moment when the leader development of the intracloud/intercloud discharge passed 0.7 km horizontally away from the radiation monitors. The intracloud/intercloud discharge started ∼15 km away from the gamma ray observation site. Therefore, the glow was terminated by the leader development, while it did not trigger the lightning discharge in the present case. This study presents high‐energy radiation, atmospheric electric field and low‐frequency radio measurements of winter thunderstorms in Japan. Long‐duration gamma ray bursts, called “gamma ray glows,” are thought to originate from electrons accelerated and multiplied by strong electric fields in thunderclouds. There are unsolved questions such as electron‐acceleration mechanisms, position of the acceleration site, lifetime, and life cycle of the bursts. We observed a gamma ray burst lasting for ∼75 s from a thundercloud abruptly terminated with a lightning discharge. The gamma ray source was destroyed by a cloud‐to‐cloud discharge over the gamma ray observation site but not related to the triggering of the discharge in the present case. A gamma ray glow and its termination with a lightning discharge was observed in a Japanese winter thunderstormThe glow was terminated by leader development of a horizontally long intracloud/intercloud discharge passing nearby overheadThe intracloud/intercloud discharge was not triggered by the glow in the present case because it started far from the gamma ray glow site

Photon detectors are an elementary tool to measure electromagnetic waves at the quantum limit1,2and are heavily demanded in the emerging quantum technologies such as communication3, sensing4and computing5. Of particular interest is a quantum non-demolition (QND)-type detector, which projects an electromagnetic wave onto the photon-number basis6–10. This is in stark contrast to conventional photon detectors2that absorb a photon to trigger a ‘click’. The long-sought QND detection of a flying photon was recently demonstrated in the optical domain using a single atom in a cavity11,12. However, the counterpart for microwaves has been elusive despite the recent progress in microwave quantum optics using superconducting circuits13–19. Here, we implement a deterministic entangling gate between a superconducting qubit and an itinerant microwave photon reflected by a cavity containing the qubit. Using the entanglement and the high-fidelity qubit readout, we demonstrate a QND detection of a single photon with the quantum efficiency of 0.84 and the photon survival probability of 0.87. Our scheme can serve as a building block for quantum networks connecting distant qubit modules as well as a microwave-photon-counting device for multiple-photon signals.

The Apollo heat flow experiment (HFE) was conducted at landing sites 15 and 17. On Apollo 15, surface and subsurface temperatures were monitored from July 1971 to January 1977. On Apollo 17, monitoring took place from December 1972 to September 1977. The investigators involved in the HFE examined and archived only data from the time of deployment to December 1974. The present authors recovered and restored major portions of the previously unarchived HFE data from January 1975 through September 1977. The HFE investigators noted that temperature of the regolith well below the reach of insolation cycles (~1 m) rose gradually through December 1974 at both sites. The restored data showed that the subsurface warming continued until the end of observations in 1977. Simultaneously, the thermal gradient decreased, because the warming was more pronounced at shallower depths. The present study has examined potential causes for the warming. Recently acquired images of the Lunar Reconnaissance Orbiter Camera over the two landing sites show that the regolith on the paths of the astronauts turned darker, lowering the albedo. We suggest that, as a result of the astronauts' activities, solar heat intake by the regolith increased slightly on average, and that resulted in the observed warming. Simple analytical heat conduction models with constant regolith thermal properties can show that an abrupt increase in surface temperature of 1.6 to 3.5 K at the time of probe deployment best duplicates the magnitude and the timing of the observed subsurface warmings at both Apollo sites. Major portions of the previously unarchived data from the Apollo heat flow experiment in 1975 through 1977 have been restoredThe newly restored data better characterize the long‐term subsurface warming at the Apollo 15 and 17 sites than previously possibleWe suggest that solar heat intake by the regolith increased slightly at the beginning of the experiment, and that resulted in the warming

Depression is a common mental disorder affecting around 350 million people worldwide. Although selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, a significant proportion of depressed patients do not achieve remission with SSRIs. In this study, we show that a serotonin type 3 receptor (5HT3R) agonist induces antidepressant effects as well as hippocampal neurogenesis independent of fluoxetine (a commonly used SSRI). Notably, our histological analysis reveals that 5HT3R and insulin-like growth factor 1 (IGF1) are expressed in the same neurons in the subgranular zone of the hippocampal dentate gyrus. Furthermore, our in vivo microdialysis analysis shows that 5HT3R regulates hippocampal extracellular IGF1 levels, and we also show that 5HT3R-dependent hippocampal neurogenesis is mediated by increased IGF1 levels. Altogether, our findings suggest a novel 5HT3R–IGF1 mechanism that is distinct from fluoxetine-induced responses and that provides a new therapeutic target for depression, especially bringing significant benefits for SSRI-resistant depressed patients.

Fabry–Perot interferometer (FPI) is an instrument that can measure the temperature and wind velocity of the thermosphere through observations of airglow emission at a wavelength of 630.0 nm. The Solar-Terrestrial Environment Laboratory/Institute for Space-Earth Environmental Research, Nagoya University, has recently developed four new ground-based FPIs. One of those FPIs, possessing a large-aperture etalon (diameter: 116 mm), was installed in Tromsø (FP01), Norway, in 2009. The other three small FPIs, using 70-mm-diameter etalons, were installed in Thailand (FP02), Indonesia (FP03) and Australia (FP04) in 2010–2011. They use highly sensitive cooled-CCD cameras with 1024 × 1024 pixels to obtain interference fringes. However, appropriate temperature has not been obtained from the interference fringes using these new small-aperture FPIs. In the present study we improved the analysis procedure of temperature determination using these FPIs. Each of FPIs measures north, south, east and west directions repeatedly by rotating two mirrors mounted on top of the FPI. We estimated center pixel of laser fringe and airglow fringes for each direction and found significant differences in the center pixel locations (a few pixels) among the measurement directions. These differences are considered to be caused by movement of the scanning mirror on the top of the optics, resulting in mechanical distortion of the optics body. By calculating the fringe center separately for each direction, we could correct these center pixel variations and determine the temperature with random errors of 10–40 K. This new method was employed to the all measurements from four FPIs after 2009 and provided temperatures with reasonably small errors. However, we found that temperatures below 400 K were obtained associated with weak airglow intensities and concluded using a model calculation that they are due to contamination of OH line emissions in the upper mesosphere. By defining an appropriate threshold of the fringe peak count, we successfully eliminated these unrealistic temperature values, and the corrected temperature values became comparable to those provided by the MSIS-90E and GAIA models.Graphical abstractTemperatures obtained by the FPIs and comparison with MSIS-E90 and GAIA models. Average temperatures (solid lines) and number of data (dashed lines) obtained at (a) Tromsø, (b) Chiang Mai, (c) Kototabang and (d) Darwin for the shown interval Thick lines show temperatures averaged for every 15 minutes obtained by FP01-04. Data obtained when the airglow intensity was very low (less than 3-sigma of CCD read-out noise) were removed. The error bars indicate standard deviations of the whole data. Thin lines and dotted lines show that obtained by the MSIS-E90 model and the GAIA model, respectively, at an altitude of 250 km.

Heart 2004;90:444-445. doi: 10.1136/hrt.2003.015354 Recently, the relation between coronary arterial remodelling and ischaemic coronary disease has become a focus of investigation. (1) Positive coronary arterial remodelling has been shown to [...]

Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, P<0.001). Significant risk factors for the development of t-AML/MDS after autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.

Asparaginase, which depletes asparagine and glutamine, activates amino-acid stress response. Oxidative stress mediated by excessive reactive oxygen species (ROS) causes enhanced mitochondrial permeabilization and subsequent cell apoptosis and is considered as a plausible mechanism for drug-induced hepatotoxicity, a common toxicity of asparaginase in adults with acute lymphoblastic leukemia (ALL). Studies investigating the pharmacogenetics of asparaginase in ALL are limited and focused on asparaginase-induced allergic reaction common in pediatric patients. Here, we sought to determine a potential association between the variant rs4880 in SOD2gene, a key mitochondrial enzyme that protects cells against ROS, and hepatotoxicity during asparaginase-based therapy in 224 patients enrolled on CALGB-10102, a treatment trial for adults with ALL. We report that the CC genotype of rs4880 is associated with increased hepatotoxicity following asparaginase-based treatment. Thus, rs4880 likely contributes to asparaginase-induced hepatotoxicity, and functional studies investigating this single-nucleotide polymorphism (SNP) are needed to develop therapeutic approaches that mitigate this toxicity.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novocopy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10−9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novoCNVs (e.g., MBD5deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novoCNVs and variable expressivity of CNVs.

Millions of patients suffer from major depressive disorder (MDD), but many do not respond to selective serotonin reuptake inhibitor (SSRI) therapy. We used a pharmacometabolomics-informed pharmacogenomics research strategy to identify genes associated with metabolites that were related to SSRI response. Specifically, 306 MDD patients were treated with citalopram or escitalopram and blood was drawn at baseline, 4 and 8 weeks for blood drug levels, genome-wide single nucleotide polymorphism (SNP) genotyping and metabolomic analyses. SSRI treatment decreased plasma serotonin concentrations (P<0.0001). Baseline and plasma serotonin concentration changes were associated with clinical outcomes (P<0.05). Therefore, baseline and serotonin concentration changes were used as phenotypes for genome-wide association studies (GWAS). GWAS for baseline plasma serotonin concentrations revealed a genome-wide significant (P=7.84E-09) SNP cluster on chromosome four 5’ of TSPAN5 and a cluster across ERICH3 on chromosome one (P=9.28E-08) that were also observed during GWAS for change in serotonin at 4 (P=5.6E-08 and P=7.54E-07, respectively) and 8 weeks (P=1.25E-06 and P=3.99E-07, respectively). The SNPs on chromosome four were expression quantitative trait loci for TSPAN5. Knockdown (KD) and overexpression (OE) of TSPAN5 in a neuroblastoma cell line significantly altered the expression of serotonin pathway genes (TPH1, TPH2, DDC and MAOA). Chromosome one SNPs included two ERICH3 nonsynonymous SNPs that resulted in accelerated proteasome-mediated degradation. In addition, ERICH3 and TSPAN5 KD and OE altered media serotonin concentrations. Application of a pharmacometabolomics-informed pharmacogenomic research strategy, followed by functional validation, indicated that TSPAN5 and ERICH3 are associated with plasma serotonin concentrations and may have a role in SSRI treatment outcomes.

In recent years the investigation of hadron structure using lattice techniques has attracted growing attention. The computation of several important quantities has become feasible. Furthermore, theoretical developments as well as progress in algorithms and an increase in computing resources have contributed to a significantly improved control of systematic errors. In this article we give an overview on the work that has been carried out in the framework of the Hadron Physics I3 (I3HP) network “Computational (lattice) hadron physics”. Here we will not restrict ourselves to spin physics but focus on results for nucleon spectrum and structure from the QCDSF collaboration. For a broader overview of developments in this field see, e.g., [1].

AimsAcetabular dysplasia is frequently associated with intra-articular pathology such as labral tears, but whether labral tears should be treated at the time of periacetabular osteotomy (PAO) remains controversial. The purpose of this study was to compare the clinical outcomes and radiographic corrections of PAO for acetabular dysplasia between patients with and without labral tears pre-operatively.Patients and MethodsWe retrospectively reviewed 70 hips in 67 patients with acetabular dysplasia who underwent PAO. Of 47 hips (45 patients) with labral tears pre-operatively, 27 (25 patients) underwent PAO alone, and were classified as the labral tear alone (LT) group, and 20 (20 patients) underwent combined PAO and osteochondroplasty, and were classified as the labral tear osteochondroplasty (LTO) group. The non-labral tear (NLT) group included 23 hips in 22 patients.ResultsThere were no significant differences between groups for post-operative Harris hip scores, degree of progression of osteoarthritis or rate of reoperation. The pre-operative alpha angle was significantly larger in the LTO group compared with the other groups (p < 0.0001).ConclusionPAO provides equivalent short-term relief of pain and functional outcome in patients with or without labral tears. The rate of progression of osteoarthritis and reoperation was not significantly increased in patients with labral tears.Take home message: PAO provides equivalent short-term pain relief and functional outcomes in patients with acetabular dysplasia with and without labral tears. We did not find significantly increased risks of progression of osteoarthritis or re-operation in those with labral tears.Cite this article: Bone Joint J2016;98-B:741–6.

Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl−1and aldosterone renin activity ratio of 90.2 (ng dl−1per ng ml−1 h−1), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl−1confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production.

AbstractIn the medium-sized heliotron device Heliotron J, edge density fluctuation has been measured simultaneously with a high-speed video camera and a Langmuir probe. Poloidally propagating, parallel elongating filamentary structures with 20- to 30-kHz frequency and ~14-cm poloidal wavelength were observed by a camera. However, the radial position of this density mode is not well known with only camera data because the camera lens axis is perpendicular to the torus plane. To identify the span of this density mode, plasma-surface interaction (PSI) between the probe and the plasma has been analyzed. As the probe scanned into the plasma, enhanced brightness due to PSI was clearly observed in camera images. By comparing this enhanced brightness among different probe positions, the outmost margin of the 20- to 30-kHz mode observed by the camera has been identified to be within 10 mm outside from the last closed flux surface. This conclusion is supported by the spectrum of the probe data.