The quest for entangled spin excitations has stimulated intense research on frustrated magnetic systems. For almost two decades, the triangular-lattice Mott insulator κ-(BEDT-TTF)
Cu
(CN)
has been ...one of the hottest candidates for a gapless quantum spin liquid with itinerant spinons. Very recently, however, this scenario was overturned as electron-spin-resonance (ESR) studies unveiled a spin gap, calling for reevaluation of the magnetic ground state. Here we achieve a precise mapping of this spin-gapped phase through the Mott transition by ultrahigh-resolution strain tuning. Our transport experiments reveal a reentrance of charge localization below T
= 6 K associated with a gap size of 30-50 K. The negative slope of the insulator-metal boundary, dT
/dp < 0, evidences the low-entropy nature of the spin-singlet ground state. By tuning the enigmatic '6K anomaly' through the phase diagram of κ-(BEDT-TTF)
Cu
(CN)
, we identify it as the transition to a valence-bond-solid phase, in agreement with previous thermal expansion and magnetic resonance studies. This spin-gapped insulating state persists at T → 0 until unconventional superconductivity and metallic transport proliferate.
Aims
A majority of children with Type 1 diabetes in Japan are registered with the government‐subsidized Specified Pediatric Chronic Disease Treatment Research Projects (SPCDTRP). In this study, the ...incidence and prevalence of childhood‐onset (< 15 years) Type 1 diabetes in Japan were estimated by drawing on SPCDTRP data.
Methods
Data available for 2005–2012 from the SPCDTRP and Statistics Bureau, Ministry of Internal Affairs and Communications were used to estimate the incidence of Type 1 diabetes for 2005–2010, adjusted to cover those registered within 3 years of disease onset and stratified by sex, age at onset and period of onset.
Results
The incidence of Type 1 diabetes for 2005–2010 was 2.25/100,000 persons 95% confidence intervals (95% CI), 2.14–2.36 (boys: 1.91, 95% CI, 1.83–1.98; girls: 2.52, 95% CI, 2.34–2.69), with that for the age brackets 0–4, 5–9 and 10–14 years being 1.48 (95% CI, 1.29–1.66), 2.27 (95% CI, 2.08–2.47) and 3.00 (95% CI, 2.74–3.25), respectively. The onset of disease was shown to peak at age 13 among boys (3.28, 95% CI, 3.02–3.55) and at age 10 among girls (3.28, 95% CI, 3.02–3.55). The peak periods of disease onset were April/May and December. The number of children aged < 15 years with Type 1 diabetes for 2005–2012 was estimated to be 2326 (95% CI, 2202–2450) with the prevalence estimated as 13.53/100,000 persons (95% CI, 12.63–14.43).
Conclusions
Study findings demonstrated no increase in the incidence of Type 1 diabetes, although suggesting, in agreement with earlier reports, that the onset of disease peaks in adolescence with a female predominance. In addition, the incidence of childhood‐onset diabetes exhibited an annual bimodal pattern in this study.
What's new?
In Japan, the incidence of childhood‐onset Type 1 diabetes for 2005–2010 was 2.3/100,000 persons, with the prevalence for 2005–2012 estimated as 13.5/100,000 persons.
In contrast to the rest of the world where the incidence has increased in recent years, particularly among those aged < 5 years, no increase diabetes in incidence has been seen in Japan since 1998.
Disease onset peaked in adolescence with a female predominance, in agreement with earlier reports.
In addition, disease onset exhibited an annual bimodal pattern peaking in April and December.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This article presents the conclusions of a WHO Expert Consultation that evaluated the utility of the ‘metabolic syndrome' concept in relation to four key areas: pathophysiology, epidemiology, ...clinical work and public health. The metabolic syndrome is a concept that focuses attention on complex multifactorial health problems. While it may be considered useful as an educational concept, it has limited practical utility as a diagnostic or management tool. Further efforts to redefine it are inappropriate in the light of current knowledge and understanding, and there is limited utility in epidemiological studies in which different definitions of the metabolic syndrome are compared. Metabolic syndrome is a pre-morbid condition rather than a clinical diagnosis, and should thus exclude individuals with established diabetes or known cardiovascular disease (CVD). Future research should focus on: (1) further elucidation of common metabolic pathways underlying the development of diabetes and CVD, including those clustering within the metabolic syndrome; (2) early-life determinants of metabolic risk; (3) developing and evaluating context-specific strategies for identifying and reducing CVD and diabetes risk, based on available resources; and (4) developing and evaluating population-based prevention strategies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A Dirac electron system in solids mimics relativistic quantum physics that is compatible with Maxwell's equations, with which we anticipate unified electromagnetic responses. We find a large orbital ...diamagnetism only along the interplane direction and a nearly temperature-independent electrical conductivity of the order of e^{2}/h per plane for the new 2D Dirac organic conductor, α-(BETS)_{2}I_{3}, where BETS is bis(ethylenedithio)tetraselenafulvalene. Unlike conventional electrons in solids whose nonrelativistic effects bifurcate electric and magnetic responses, the observed orbital diamagnetism scales with the electrical conductivity in a wide temperature range. This demonstrates that an electromagnetic duality that is valid only within the relativistic framework is revived in solids.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
A brief review is given on the controversy and its solution about the fact that the angular momentum vector of protons and that of neutrons in well-deformed nuclei at low total angular momenta have a ...strong correlation that they are oriented in opposite directions. In a simple two-rotor model in 2-dimensional space, this fact is explained as originating from the quantum mechanical uncertainty relation between the angle and the angular momentum for the relative rotation of the two rotors. As the second topic, a more realistic model consisting of two triaxial rotors in 3-dimensional space coupled with a QQ interaction is employed to investigate a possible shears-band-like collective rotation predicted by T. Otsuka, in which the angle at which the angular momentum of protons and that of neutrons intersect changes continuously from 180° at spin zero toward 0° at high spins within the same rotational band. The probability distributions of the angle between the two angular momenta and the angle between the longest principal axes of two rotors are calculated to examine the participation of the scissors mode in the evolution of the ground rotational band versus spin.
The cyanobacterium, Synechocystis sp. PCC 6803, was the first photosynthetic organism whose genome sequence was determined in 1996 (Kazusa strain). It thus plays an important role in basic research ...on the mechanism, evolution, and molecular genetics of the photosynthetic machinery. There are many substrains or laboratory strains derived from the original Berkeley strain including glucose-tolerant (GT) strains. To establish reliable genomic sequence data of this cyanobacterium, we performed resequencing of the genomes of three substrains (GT-I, PCC-P, and PCC-N) and compared the data obtained with those of the original Kazusa strain stored in the public database. We found that each substrain has sequence differences some of which are likely to reflect specific mutations that may contribute to its altered phenotype. Our resequence data of the PCC substrains along with the proposed corrections/refinements of the sequence data for the Kazusa strain and its derivatives are expected to contribute to investigations of the evolutionary events in the photosynthetic and related systems that have occurred in Synechocystis as well as in other cyanobacteria.
EUSO-TA is a ground-based fluorescence telescope built to validate the design of ultra-high energy cosmic ray fluorescence detectors to be operated in space with the technology developed within the ...Joint Exploratory Missions for Extreme Universe Space Observatory (JEM-EUSO) program. It operates at the Telescope Array (TA) site in Utah, USA. With an external trigger provided by the Black Rock Mesa fluorescence detectors of the Telescope Array experiment, with EUSO-TA we observed air-showers from ultra-high energy cosmic rays, as well as laser events from the Central Laser Facility at the TA site and from portable lasers like the JEM-EUSO Global Light System prototype. Since the Black Rock Mesa fluorescence detectors have a ∼30 times larger field of view than EUSO-TA, they allow a primary energy reconstruction based on the observation of a large part of the shower evolution, including the shower maximum, while EUSO-TA observes only a part of it, usually far away from the maximum. To estimate the detection limits of EUSO-TA in energy and distance, a method was developed to re-scale their energy, taking into account that EUSO-TA observes only a portion of the air-showers. The method was applied on simulation sets with showers with different primaries, energy, direction, and impact point on the ground, as well as taking into account the experimental environment. EUSO-TA was simulated with an internal trigger and different elevation angles and electronics. The same method was then applied also to real measurements and compared to the simulations. In addition, the method can also be used to estimate the detection limits for experiments that are operated at high altitudes and in most cases can see the maximum of the showers. This was done for EUSO-SPB1, an instrument installed on a super-pressure balloon. Finally, the expected detection rates for EUSO-TA were also assessed using the prepared simulated event sets. The rates correspond to a few detections per recording session of 30 h of observation, depending on the background level and the configuration of the detector.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pressure dependence of the conductivity and thermoelectric power is measured through the Mott transition in the layer organic conductor EtMe_{3}PPd(dmit)_{2}_{2}. The critical behavior of the ...thermoelectric effect provides a clear and objective determination of the Mott-Hubbard transition during the isothermal pressure sweep. Above the critical end point, the metal-insulator crossing, determined by the thermoelectric effect minimum value, is not found to coincide with the maximum of the derivative of the conductivity as a function of pressure. We show that the critical exponents of the Mott-Hubbard transition fall within the Ising universality class regardless of the dimensionality of the system.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Abstract
Background: Human epidermal growth factor receptor 3 (HER3) is overexpressed in a variety of solid tumors, including breast cancer. However, there are no approved HER3-targeted anti-cancer ...therapies. U3-1402 is a HER3-targeted antibody drug conjugate with a novel peptide-based cleavable linker attached to a potent topoisomerase I inhibitor payload. It has a high drug-to-antibody ratio (7:1 to 8:1), a novel linker which is stable in plasma and selectively cleaved by lysosomal cathepsins up-regulated in cancer cells, and a payload with a short systemic half-life. The ongoing, phase 1/2 study (NCT02980341) was initiated to evaluate the safety, tolerability, and efficacy of U3-1402 in HER3-overexpressing metastatic breast cancer (MBC). The study has 3 parts: Dose Escalation, Dose Finding, and Dose Expansion. Here we report updated results from Dose Escalation and Dose Finding.
Methods: In Dose Escalation, the dose of U3-1402 was escalated based on dose-limiting toxicity data (between 1.6 and 8.0 mg/kg) and guided by the modified Continuous Reassessment Method. In Dose Finding, patients were treated with 1 of 2 doses (4.8 mg/kg or 6.4 mg/kg) identified during Dose Escalation. In both parts, U3-1402 was administered via IV infusion in 21-day cycles. The primary objectives were to determine the safety and tolerability of U3-1402, the maximum tolerated dose (MTD), and the recommended dose for expansion. Efficacy assessments included investigator-assessed objective response rate (ORR; proportion of complete response CR + partial response PR) per RECIST v1.1 and disease control rate (DCR; proportion of CR + PR + stable disease). Efficacy-evaluable patients received ≥1 dose of U3-1402 and had pre- and post-treatment tumor assessments. Pharmacokinetics and the anti-drug antibodies were also assessed.
Results: As of 1 June 2018, a total of 42 patients received U3-1402 across Dose Escalation and Dose Finding (34 and 8 patients, respectively). Overall, 12 patients have discontinued treatment (9 due to progressive disease, 1 due to clinical progression, 1 due to Grade 2 pneumonitis, and 1 due to withdrawal of consent). A total of 30 patients remain on treatment (33.3% 14/42 for ≥6 months). The median (range) age was 54.5 (30–81), and majorities of patients had an ECOG performance status of 0 (76.2%; 32/42) and had received ≥5 prior anti-cancer regimens (78.6%; 33/42). Among efficacy-evaluable patients, the ORR was 46.3% (19/41) and the DCR was 90.2% (37/41). Grade ≥3 treatment-related AEs (TEAEs) were reported in 61.9% (26/42) patients. TEAEs (>50% in treated patients) regardless of causality (any grade, Grade ≥3) included nausea (83.3%, 4.8%), thrombocytopenia (71.4%, 33.3%), decreased appetite (64.3%, 7.1%), neutropenia (59.5%, 26.2%), and leukopenia (57.1%, 19.0%). The MTD was not reached; dose limiting toxicities included events of decreased platelet count and increases in AST or ALT.
Conclusions: In a preliminary analysis of this ongoing phase 1/2 clinical trial, U3-1402 demonstrated antitumor activity in a substantial number of heavily pretreated HER3-expressing MBC patients, and U3-1402 treatment was associated with a manageable safety profile.
Citation Format: Masuda N, Yonemori K, Takahashi S, Kogawa T, Nakayama T, Iwase H, Takahashi M, Toyama T, Saeki T, Saji S, Inoue K, Onuma H, Tajima N, Shiose Y, Chen S, Guevara F, Yu C, Ueno S, Iwata H. Single agent activity of U3-1402, a HER3-targeting antibody-drug conjugate, in HER3-overexpressing metastatic breast cancer: Updated results of a phase 1/2 trial abstract. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD1-03.
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