Right adrenal vein identification using unenhanced magnetic resonance imaging

Purpose: Unenhanced magnetic resonance imaging (MRI) is known to be useful in characterizing adrenal adenomas through the implementation of in-phase (IPI) and opposed-phase imaging (OPI) based on chemical shift artifacts. However, whether unenhanced MRI can contribute to the identification of right adrenal vein (RAV) remains unclear. The aim of this study was to evaluate the feasibility of unenhanced MRI for the identification of RAV. Material and methods: This retrospective study reviewed 30 patients (16 men; median age 60 years; range 34-76 years) who underwent MRI and subsequent adrenal venous sampling (AVS). Chemical shift MRI was acquired using echo times of 2.3 ms (OPI) and 4.6 ms (IPI) with a slice thickness of 3 mm and a gap of 1 mm. T2-weighted imaging (T2WI) was also performed. Identification of RAVs was performed by 2 independent radiologists. Inter-observer agreement on a 3-point rating scale was evaluated using κ statistics. The identification rate of RAVs was compared between OPI, IPI, and T2WI using McNemar’s test. Results: Good inter-observer agreement was found for the OPI (κ = 0.744), whereas fair agreement was obtained for both other sequences (IPI: κ = 0.375; T2WI: 0.348). For both raters, the identification rate of RAVs was higher with OPI (36/60; 60.0%) than with other sequences (IPI: 16/60, 26.7%; T2WI: 9/60, 15.0%; p < 0.05, each). Conclusions: OPI may play a screening role in the identification of RAVs preceding AVS, which could reduce the required radiation exposure and doses of contrast agent

A Great Space Weather Event in February 1730

Aims. Historical records provide evidence of extreme magnetic storms with equatorward auroral extensions before the epoch of systematic magnetic observations. One significant magnetic storm occurred on February 15, 1730. We scale this magnetic storm with auroral extension and contextualise it based on contemporary solar activity. Methods. We examined historical records in East Asia and computed the magnetic latitude (MLAT) of observational sites to scale magnetic storms. We also compared them with auroral records in Southern Europe. We examined contemporary sunspot observations to reconstruct detailed solar activity between 1729 and 1731. Results. We show 29 auroral records in East Asian historical documents and 37 sunspot observations. Conclusions. These records show that the auroral displays were visible at least down to 25.8{\deg} MLAT throughout East Asia. In comparison with contemporary European records, we show that the boundary of the auroral display closest to the equator surpassed 45.1{\deg} MLAT and possibly came down to 31.5{\deg} MLAT in its maximum phase, with considerable brightness. Contemporary sunspot records show an active phase in the first half of 1730 during the declining phase of the solar cycle. This magnetic storm was at least as intense as the magnetic storm in 1989, but less intense than the Carrington event.Comment: 30 pages, 5 figures, and 2 tables, accepted for publication in Astronomy & Astrophysics on 25 April 2018. The figures and transcriptions/translations of historical documents are partially omitted in this manuscript due to the condition of reproduction. They are available in the publisher versio

Strategic use of new generation antidepressants for depression: SUN(^_^) D protocol update and statistical analysis plan

Background: SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multicenter pragmatic mega-trial to examine the optimum treatment strategy for the first- and second-line treatments for unipolar major depressive episodes. The trial has three steps and two randomizations. Step I randomization compares the minimum and the maximum dosing strategy for the first-line antidepressant. Step II randomization compares the continuation, augmentation or switching strategy for the second-line antidepressant treatment. Step III is a naturalistic continuation phase. The original protocol was published in 2011, and we hereby report its updated protocol including the statistical analysis plan. Results: We implemented two important changes to the original protocol. One is about the required sample size, reflecting the smaller number of dropouts than had been expected. Another is in the organization of the primary and secondary outcomes in order to make the report of the main trial results as pertinent and interpretable as possible for clinical practices. Due to the complexity of the trial, we plan to report the main results in two separate reports, and this updated protocol and the statistical analysis plan have laid out respective primary and secondary outcomes and their analyses. We will convene the blind interpretation committee before the randomization code is broken. Conclusion: This paper presents the updated protocol and the detailed statistical analysis plan for the SUN(^_^)D trial in order to avoid reporting bias and data-driven results. Trial registration: ClinicalTrials.gov: NCT01109693(registered on 21 April 2010)

Association between shift work and the risk of death from biliary tract cancer in Japanese men

Background: There is increasing evidence suggesting that shift work involving night work may increase cancer risk. Methods: We examined the association between working rotating shifts and the risk of death from biliary tract cancer among Japanese men who participated in the Japan Collaborative Cohort Study. Of the 46, 395 men recruited, 22, 224 men aged 40-65 at baseline (1988-1990) who reported working full-time or were self-employed were included in the present analysis. The study subjects were followed through December 31, 2009. Information regarding occupation and lifestyle factors was collected using a self-administered questionnaire. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for the risk of death from biliary tract cancer in relation to shift work. Results: During a mean 17-year follow-up, we observed 94 biliary tract cancer deaths, including 23 deaths from gallbladder cancer and 71 deaths from extrahepatic bile duct cancer. Overall, shift work was associated with a statistically non-significant increase in the risk of biliary tract cancer, with an HR of 1.50 (95 % CI: 0.81-2.77), among rotating shift workers. When the analysis was limited to extrahepatic bile duct cancer, a significant association appeared, with a multivariable-adjusted HR of 1.93 (95 % CI: 1.00-3.72) for rotating shift workers. Conclusion: Our data indicate that shift work may be associated with increased risk of death from extrahepatic bile duct cancer in this cohort of Japanese men. The association with gallbladder cancer remains unclear because of the small number of deaths

Bortezomib-cyclophosphamide-dexamethasone induction/consolidation and bortezomib maintenance for transplant-eligible newly diagnosed multiple myeloma: phase 2 multicenter trial

[Objectives:] We conducted a phase II trial to prospectively evaluate the efficacy and safety of bortezomib-cyclophosphamide-dexamethasone (VCD) induction, autologous stem cell transplantation (ASCT), VCD consolidation, and bortezomib maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients in Japan (UMIN000010542). [Methods:] From 2013 to 2016, 42 patients with a median age of 58 (range 42–65) years with NDMM were enrolled in 15 centers. The primary endpoint was the complete response (CR) /stringent CR (sCR) rate after transplantation, and overall/progression-free survival rates were also evaluated. [Results:] Following induction therapy, the overall response rate was obtained in 71% of patients, including a CR/sCR of 10% and a very good partial response (VGPR) of 26%. Twenty-six of the 42 patients completed ASCT following the protocol and CR/sCR and VGPR rate 100 days after ASCT was 26% and 17%, respectively. During consolidation therapy, 3 of the 24 patients achieved deeper responses. Eight of the 18 patients completed 2-year bortezomib maintenance without disease progression and grade 3/4 toxicities. Five patients were VGPR or partial response after ASCT but maintained response with 2-year bortezomib maintenance. Two-year overall and progression-free survival rates were 92.5% (95% confidence interval [CI]: 78.5%−97.5%) and 62.6% (95% CI: 45.8%−75.5%), respectively. Grade 3/4 toxicities (≥ 10%) included neutropenia (19%) and anemia (17%) in induction, and thrombocytopenia (29%) in consolidation. [Conclusion:] VCD induction/consolidation and bortezomib maintenance with ASCT for NDMM resulted in a high CR/sCR rate and provided good overall/progression-free survival in Japan

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies