Erratum: Large Unidirectional Magnetoresistance in a Magnetic Topological Insulator [Phys. Rev. Lett. 117, 127202 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.127202.

Predictive performance of a genetic risk score using 11 susceptibility alleles for the incidence of Type 2 diabetes in a general Japanese population: a nested case-control study.

AIMS: To assess the predictive ability of a genetic risk score for the incidence of Type 2 diabetes in a general Japanese population. METHODS: This prospective case-control study, nested within a Japan Public Health Centre-based prospective study, included 466 participants with incident Type 2 diabetes over a 5-year period (cases) and 1361 control participants, as well as 1463 participants with existing diabetes and 1463 control participants. Eleven susceptibility single nucleotide polymorphisms, identified through genome-wide association studies and replicated in Japanese populations, were analysed. RESULTS: Most single nucleotide polymorphism loci showed directionally consistent associations with diabetes. From the combined samples, one single nucleotide polymorphism (rs2206734 at CDKAL1) reached a genome-wide significance level (odds ratio 1.28, 95% CI 1.18-1.40; P = 1.8 × 10-8 ). Three single nucleotide polymorphisms (rs2206734 in CDKAL1, rs2383208 in CDKN2A/B, and rs2237892 in KCNQ1) were nominally significantly associated with incident diabetes. Compared with the lowest quintile of the total number of risk alleles, the highest quintile had a higher odds of incident diabetes (odds ratio 2.34, 95% CI 1.59-3.46) after adjusting for conventional risk factors such as age, sex and BMI. The addition to the conventional risk factor-based model of a genetic risk score using the 11 single nucleotide polymorphisms significantly improved predictive performance; the c-statistic increased by 0.021, net reclassification improved by 6.2%, and integrated discrimination improved by 0.003. CONCLUSIONS: Our prospective findings suggest that the addition of a genetic risk score may provide modest but significant incremental predictive performance beyond that of the conventional risk factor-based model without biochemical markers.

X-ray absorption near edge structure and first-principles spectral investigations of cationic disorder in MgAl2O4 induced by swift heavy ions.

Cationic disorder in the MgAl2O4 spinel induced by swift heavy ions was investigated using the X-ray absorption near edge structure. With changes in the irradiation fluences of 200 MeV Xe ions, the Mg K-edge and Al K-edge spectra were synchronously changed. The calculated spectra based on density function theory indicate that the change in the experimental spectra was due to cationic disorder between Mg in tetrahedral sites and Al in octahedral sites. These results suggest a high inversion degree to an extent that the completely random configuration is achieved in MgAl2O4 induced by the high density electronic excitation under swift heavy ion irradiation.

Integrating quantitative morphological and intratumoural textural characteristics in FDG-PET for the prediction of prognosis in pharynx squamous cell carcinoma patients.

AIM: To assess potential prognostic factors in pharynx squamous cell carcinoma (SCC) patients by quantitative morphological and intratumoural characteristics obtained by 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: The cases of 54 patients with pharynx SCC who underwent chemoradiation therapy were analysed retrospectively. Using their FDG-PET data, the quantitative morphological and intratumoural characteristics of 14 parameters were calculated. The progression-free survival (PFS) and overall survival (OS) information was obtained from patient medical records. Univariate and multivariate analyses were performed to assess the 14 quantitative parameters as well as the T-stage, N-stage, and tumour location data for their relation to PFS and OS. When an independent predictor was suggested in the multivariate analysis, the parameter was further assessed using the Kaplan-Meier method. RESULTS: In the assessment of PFS, the univariate and multivariate analyses indicated the following as independent predictors: the texture parameter of homogeneity and the morphological parameter of sphericity. In the Kaplan-Meier analysis, the PFS rate was significantly improved in the patients who had both a higher value of homogeneity (p=0.01) and a higher value of sphericity (p=0.002). With the combined use of homogeneity and sphericity, the patients with different PFS rates could be divided more clearly. CONCLUSION: The quantitative parameters of homogeneity and sphericity obtained by FDG-PET can be useful for the prediction of the PFS of pharynx SCC patients, especially when used in combination.

Equine faecal microbiota transplant: Current knowledge, proposed guidelines and future directions.

While certainly not a novel concept, faecal microbiota transplant (FMT) has recently garnered renewed interest in veterinary medicine due to its remarkable success in treating recurrent Clostridium difficile infection (CDI) in man. There is a dearth of information on indications and efficacy of FMT for the treatment of gastrointestinal disorders in the horse; however, based on evidence in man and other veterinary species, and anecdotal reports in horses, FMT may be a useful treatment for selected cases of acute and chronic diarrhoea and inflammatory bowel disease (IBD) in the horse. In the absence of evidence, expert opinion is offered on case selection and FMT procedure. More research is needed to explore the efficacy, indications and optimal preparation, storage and delivery of FMT to horses.

Current-Nonlinear Hall Effect and Spin-Orbit Torque Magnetization Switching in a Magnetic Topological Insulator.

The current-nonlinear Hall effect or second harmonic Hall voltage is widely used as one of the methods for estimating charge-spin conversion efficiency, which is attributed to the magnetization oscillation by spin-orbit torque (SOT). Here, we argue the second harmonic Hall voltage under a large in-plane magnetic field with an in-plane magnetization configuration in magnetic-nonmagnetic topological insulator (TI) heterostructures, Cr_{x}(Bi_{1-y}Sb_{y})_{2-x}Te_{3}/(Bi_{1-y}Sb_{y})_{2}Te_{3}, where it is clearly shown that the large second harmonic voltage is governed not by SOT but mainly by asymmetric magnon scattering without macroscopic magnetization oscillation. Thus, this method does not allow an accurate estimation of charge-spin conversion efficiency in TI. Instead, the SOT contribution is exemplified by current pulse induced nonvolatile magnetization switching, which is realized with a current density of 2.5×10^{10} A m^{-2}, showing its potential as a spintronic material.

Large Unidirectional Magnetoresistance in a Magnetic Topological Insulator.

We report current-direction dependent or unidirectional magnetoresistance (UMR) in magnetic or nonmagnetic topological insulator (TI) heterostructures, Cr_{x}(Bi_{1-y}Sb_{y})_{2-x}Te_{3}/(Bi_{1-y}Sb_{y})_{2}Te_{3}, that is several orders of magnitude larger than in other reported systems. From the magnetic field and temperature dependence, the UMR is identified to originate from the asymmetric scattering of electrons by magnons. In particular, the large magnitude of UMR is an outcome of spin-momentum locking and a small Fermi wave number at the surface of TI. In fact, the UMR is maximized around the Dirac point with the minimal Fermi wave number.

Appendiceal orifice inflammation is associated with proximal extension of disease in patients with ulcerative colitis.

AIM: Ulcerative colitis (UC) is considered to be a disease of continuous mucosal inflammation extending proximally from the rectum. However, appendiceal orifice inflammation (AOI) is a skip lesion with segments of continuous involvement from the rectum. The aim of this study was to examine the clinical characteristics and clinical course, particularly focused on proximal extension, of UC in patients with AOI. METHOD: A retrospective evaluation of patients with UC who underwent total colonoscopy at the Department of Surgical Oncology, The University of Tokyo, from 2004 to 2014. The degree of AOI was graded endoscopically as follows: 0 (no inflammation); 1 (slight oedema); 2 (moderate inflammation); and 3 (marked inflammation). A total of 189 patient records were reviewed retrospectively. The presence of AOI was analysed with regard to the clinical information of each patient, and its association with proximal extension of proctitis or left-sided colitis was evaluated. RESULTS: Of 189 patients with UC who underwent total colonoscopy at our institution, 92 were diagnosed with pancolitis, 50 with left-sided colitis and 47 with proctitis. Endoscopic findings of AOI were observed in 26 patients, including 11 (12.0%) with pancolitis, six (12.0%) with left-sided colitis and nine (19.1%) with proctitis. During follow up, proximal extension of the disease occurred in all nine patients with proctitis AOI. CONCLUSION: AOI is more frequently observed in patients with proctitis. Our results showed correlations between AOI and subsequent proximal extension of mucosal inflammation in patients with proctitis.

Early optimization of antimicrobial therapy improves clinical outcomes of patients administered agents targeting methicillin-resistant Staphylococcus aureus.

WHAT IS KNOWN AND OBJECTIVE: Antimicrobial stewardship is required to ensure the appropriate use of antimicrobials. However, no reports have been published on clinical outcomes of implementation of antimicrobial stewardship in patients receiving pathogen-specific antibiotics. METHOD: To evaluate the clinical outcomes of patients who received drugs, we conducted a single-centre, retrospective study of the effects of an antimicrobial stewardship programme targeting methicillin-resistant Staphylococcus aureus (MRSA). RESULTS: The time to administer effective antimicrobials was significantly (median number of days, 3 before vs. 0 after, P < 0·001) shortened, and the rate of de-escalation was significantly elevated (47·1% vs. 96·2%, P < 0·001) after implementation of daily review. The 60-day clinical failure associated with Gram-positive bacterial infection was significantly reduced (33·3% vs. 17·6%, P = 0·007) after intervention. WHAT IS NEW AND CONCLUSIONS: Daily review of administration of antimicrobials targeting MRSA was highly effective in improving clinical outcomes by optimizing early antimicrobial therapy.

Sweet potato resistance to Euscepes postfasciatus (Coleoptera: Curculionidae): larval performance adversely effected by adult's preference to tuber for food and oviposition.

The preferences of the West Indian sweet potato weevil, Euscepes postfasciatus (Fairmaire), to tubers of sweet potato, Ipomoea batatas (L.), for food and for oviposition were evaluated, and correlated to sweet potato's resistance to immatures. Adults (parent) were released in a plastic box containing tubers of sweet potato cultivars and maintained for 5 d, after which the adults on each tuber were counted. All adults were then removed and each tuber was maintained separately. New adults that emerged from the tubers were counted. Cultivars were grouped by cluster analyses using the number of parent adults on the tubers and the number of new adults emerging from the tubers, adjusted for the weight of each tuber. Cultivars were divided into five groups: average level of preference, preferred, preferred for oviposition but not for food, preferred for food but not for oviposition, and not preferred. New adults from the first two groups took less time to eclose than those from the other groups, and their body size was smaller. In a second experiment, one to five cultivars were selected from each group and inoculated each tuber with 10 weevil eggs on each cultivar. Although the proportion of eclosed adults was not significantly different between cultivars, the time to eclosion was shorter and body size was smaller on preferred cultivars. The selection of tubers by parent adults was not linearly related with larval development, and did not reduce the survival of the immatures.

Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer.

BACKGROUND: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). METHODS: Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg m(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy). RESULTS: One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions. CONCLUSION: We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.

Peroral video cholangioscopy to evaluate indeterminate bile duct lesions and preoperative mucosal cancerous extension: a prospective multicenter study.

BACKGROUND AND STUDY AIMS: Despite the development of peroral video cholangioscopy (PVCS), no prospective multicenter studies have been undertaken to investigate the diagnostic accuracy of PVCS in biliary tract diseases. Therefore, the aim of this study was to clarify the accuracy of PVCS in evaluating biliary tract lesions. PATIENTS AND METHODS: This study was a prospective multicenter study at five tertiary referral centers in Japan and included 87 eligible patients with biliary tract diseases who underwent PVCS. The study evaluated the ability of PVCS to diagnose indeterminate biliary tract diseases, detect mucosal cancerous extension preoperatively in extrahepatic bile duct cancers, and predict adverse events. RESULTS: The use of PVCS appearance alone correctly distinguished benign from malignant indeterminate biliary lesions in 92.1 % of patients whereas biopsy alone was accurate in 85.7 %. In extrahepatic bile duct cancer, mucosal cancer extended histologically at least 20 mm in 34.7 % (17/49) of patients. The accuracy rate of PVCS to evaluate the presence or absence of mucosal cancerous extension by endoscopic retrograde cholangiography (ERC) alone, ERC with PVCS, and ERC with PVCS + biopsy were 73.5 %, 83.7 %, and 92.9 %, respectively. Adverse events were seen in 6.9 % of PVCS patients, but no serious complications were observed. CONCLUSION: PVCS enhanced the accurate diagnosis of biliary tract lesions by providing excellent resolution in combination with biopsy.

Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression.

Variation in the CYP3A enzymes, which act in drug metabolism, influences circulating steroid levels and responses to half of all oxidatively metabolized drugs. CYP3A activity is the sum activity of the family of CYP3A genes, including CYP3A5, which is polymorphically expressed at high levels in a minority of Americans of European descent and Europeans (hereafter collectively referred to as 'Caucasians'). Only people with at least one CYP3A5*1 allele express large amounts of CYP3A5. Our findings show that single-nucleotide polymorphisms (SNPs) in CYP3A5*3 and CYP3A5*6 that cause alternative splicing and protein truncation result in the absence of CYP3A5 from tissues of some people. CYP3A5 was more frequently expressed in livers of African Americans (60%) than in those of Caucasians (33%). Because CYP3A5 represents at least 50% of the total hepatic CYP3A content in people polymorphically expressing CYP3A5, CYP3A5 may be the most important genetic contributor to interindividual and interracial differences in CYP3A-dependent drug clearance and in responses to many medicines.

Esophageal submucosal dissection under steady pressure automatically controlled endoscopy (SPACE): a randomized preclinical trial.

BACKGROUND AND STUDY AIMS: A new overtube system has been developed for steady pressure automatically controlled endoscopy (SPACE) in the gastrointestinal tract. The objectives of this study were to validate the feasibility and safety of SPACE in the esophagus, and to evaluate its potential advantages over conventional (manually insufflating) endoscopy in endoscopic submucosal dissection (ESD). METHODS: This was a multicenter preclinical trial using acute porcine models (n = 20). In Experiment 1 (feasibility/safety study), SPACE was attempted in the esophagus with continuous monitoring of cardiopulmonary parameters and intraluminal pressures in the downstream bowel. Different insufflation pressures were tested to optimize the insufflation condition. Each session was video-recorded and scored by blinded reviewers. In Experiment 2 (randomized trial), esophageal ESD was attempted using either SPACE or conventional endoscopy, and results were compared. RESULTS: In Experiment 1, SPACE was performed safely without intraluminal pressure elevation in the downstream bowel. According to video review, SPACE provided more stable, reproducible, and rapid visualization than conventional endoscopy. The insufflation pressure was optimized at 14 mmHg for esophageal SPACE. In Experiment 2, ESD was completed in all animals. The ESD time was significantly shorter with SPACE compared with conventional endoscopy (1326 vs. 1616 seconds; P = 0.009). Responses to questionnaires showed that 94 % - 100 % of participants considered SPACE to provide improved exposure and more uniform tissue tension than conventional endoscopy. Other data were comparable. CONCLUSIONS: SPACE is feasible, safe, and potentially effective for complicated endoscopic procedures, such as ESD. SPACE improves and standardizes endoscopic exposure and tissue tension. A clinical study is required to further confirm its safety and clinical effectiveness.

Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5.

OBJECTIVES: The main histological change in rheumatoid arthritis (RA) is the villous proliferation of synovial lining cells, an important source of cytokines and chemokines, which are associated with inflammation. The aim of this study was to evaluate gene expression in the microdissected synovial lining cells of RA patients, using those of osteoarthritis (OA) patients as the control. METHODS: Samples were obtained during total joint replacement from 11 RA and five OA patients. Total RNA from the synovial lining cells was derived from selected specimens by laser microdissection (LMD) for subsequent cDNA microarray analysis. In addition, the expression of significant genes was confirmed immunohistochemically. RESULTS: The 14 519 genes detected by cDNA microarray were used to compare gene expression levels in synovial lining cells from RA with those from OA patients. Cluster analysis indicated that RA cells, including low- and high-expression subgroups, and OA cells were stored in two main clusters. The molecular activity of RA was statistically consistent with its clinical and histological activity. Expression levels of signal transducer and activator of transcription 1 (STAT1), interferon regulatory factor 1 (IRF1), and the chemokines CXCL9, CXCL10, and CCL5 were statistically significantly higher in the synovium of RA than in that of OA. Immunohistochemically, the lining synovium of RA, but not that of OA, clearly expressed STAT1, IRF1, and chemokines, as was seen in microarray analysis combined with LMD. CONCLUSIONS: Our findings indicate an important role for lining synovial cells in the inflammatory and proliferative processes of RA. Further understanding of the local signalling in structural components is important in rheumatology.

Estimating production costs and retail prices in different poultry housing systems: conventional, enriched cage, aviary, and barn in Japan.

For many producers, introduction of improved animal welfare systems is a turning point in their future production strategies as it increases production costs. The increase in egg retail prices is of growing concern not only for producers, but also for retailers and consumers. However, no report has calculated the estimated production costs or retail prices associated with introducing practices that support improved animal welfare in poultry farms in Japan. Therefore, this study aimed to estimate the production costs and table egg prices of 6 types of laying hen systems: conventional cage (CC): 8- and 12-tiers (CC8, CC12), enriched cage (EC): 8- and 12-tiers (EC8, EC12), aviary (AV), and barn systems (BR). Production costs include land purchases, construction costs of facilities, equipment and machinery, quantity of feed provided, farming materials invested, and wages. As a result, farm gate prices were estimated as CC8 = 12.19, CC12 = 12.19, EC8 = 14.52, EC12 = 14.52, AV = 21.14, and BR = 28.74 [yen/egg], and the production cost, including building the new farm, increased by EC8 = 19.1%, EC12 = 19.1%, AV = 73.4%, and BR = 135.7%, respectively, referring to the value of CC. The results show that the prices increase in systems between CC and BN. The retail price or table egg price was estimated to be CC8 = 24.68, CC12 = 24.68, EC8 = 28.07, EC12 = 28.07, AV = 37.27, and BR = 48.53 [yen/egg]. The retail price of BR is approximately twice that of CC. In addition, assuming that all of Japan's eggs were produced in the BR system, the soaring cost of eggs would likely affect the prices of factory eggs, such as liquid eggs and other products, thus affecting the prices of various food products. Understanding the significant management costs that affect the retail price of eggs would facilitate improved policies and practical approaches to support poultry farms and sustainable farming activities while addressing public concerns.

Impaired fracture healing in macrophage migration inhibitory factor-deficient mice.

UNLABELLED: This study investigated the role of macrophage migration inhibitory factor (MIF) in fracture repair using MIF gene-deficient mice (MIF KO). Fracture healing was delayed in MIF KO, and this was mainly due to the delay in the mineralization of osteoid within the fracture callus. INTRODUCTION: We previously reported that the expression of macrophage migration inhibitory factor (MIF) was up-regulated during the fracture healing process in rats. However, its role in the pathophysiology of this process remained unclear. The aim of the present study was to clarify the role of MIF in the fracture healing process using MIF gene-deficient mice (MIF KO). METHODS: Bone repair in wild-type mice (WT) and MIF KO (n = 70, respectively) was investigated using a tibia fracture model. Radiographic, biomechanical, histological, bone histomorphometric, and molecular analyses were performed. RESULTS: Post-fracture biomechanical testing showed that maximum load and stiffness were significantly lower in MIF KO than in WT on day 42. However, similar levels were observed between the two groups on day 84. Bone histomorphometric analysis revealed significantly higher osteoid volume, a lower mineral apposition rate, and smaller numbers of osteoclasts in the MIF KO callus compared to the WT callus. The messenger ribonucleic acid expressions of matrix metalloproteinase (MMP)-2, membranous type 1-MMP, cathepsin K, and tissue nonspecific alkaline phosphatase were found to be significantly suppressed in the MIF KO callus. CONCLUSION: The results of the present study suggest that delayed fracture healing in MIF KO was mainly attributable to a delay in osteoid mineralization.

Ascorbic acid enrichment of whole potato tuber by vacuum-impregnation.

The aim of this study was to evaluate the use of vacuum-impregnation (VI) for enriching the ascorbic acid content of whole potatoes. Whole potatoes were immersed in a 10% ascorbic acid (AA) solution. A vacuum pressure of 70cm Hg was applied for 0-60min, following atmospheric pressure restoration for 3h, while samples remained in the VI solution. AA concentrations of potatoes were measured using HPLC. The effects of cooking and storage time in subsets of the fortified samples were also evaluated. Results indicated that the AA concentration of whole potatoes increased with vacuum time (max 150mg/100g fr. wt.). In addition, a steam-cooking study showed that 100g of the 25min steam-cooked VI potatoes could provide adults with 90-100% of the recommended daily allowance of AA (100mg). The storage study showed that VI whole potatoes had a relatively high AA concentration (50mg/100gfr. wt.), even at 14days of storage at 4°C. This study indicated that VI treatment of whole potatoes was useful for enriching the AA content.

A survey on diarrhea and convenience of intake associated with a single-dose extended release formulation of azithromycin.

The development of a single-dose extended release formulation of azithromycin (AZ-SR) improves the adherence. However, gastrointestinal side effects such as diarrhea are frequent adverse drug reactions. The aim of the present study was to investigate the incidence of patient-reported in a diarrhea and the convenience of intake of AZ-SR in an Asian population. To assess the incidence of diarrhea and convenience of intake, patient-reported in a questionnaire about the incidence, onset, duration and severity of diarrhea, shape of stool, and patients' impression on taste. The drug was prepared and used in common with the hospital pharmacy and the community pharmacy. AZ-SR was prescribed in 96 outpatients, among whom 81 patients received the medicine and the questionnaire at the hospital pharmacy or one of five neighboring community pharmacies. The recovery of the questionnaire was 40.7%. Diarrhea occurred in 18 of 33 patients (54.5%), which was more frequent than in earlier reports, although the symptom was mild (grade 1-2) and occurred in most cases within 2 days. Approximately one third of patients reported inconvenience in taking the formulation in respect of the ease (36.4%), amount (42.4%), and unpleasant bitter taste (36.4%). We report here the importance of collaboration between hospital pharmacists and community pharmacists in providing accurate drug information, including the incidence of diarrhea, to patients receiving AZ-SR.