Incoherent transport across the strange-metal regime of overdoped cuprates.

Strange metals possess highly unconventional electrical properties, such as a linear-in-temperature resistivity1-6, an inverse Hall angle that varies as temperature squared7-9 and a linear-in-field magnetoresistance10-13. Identifying the origin of these collective anomalies has proved fundamentally challenging, even in materials such as the hole-doped cuprates that possess a simple bandstructure. The prevailing consensus is that strange metallicity in the cuprates is tied to a quantum critical point at a doping p* inside the superconducting dome14,15. Here we study the high-field in-plane magnetoresistance of two superconducting cuprate families at doping levels beyond p*. At all dopings, the magnetoresistance exhibits quadrature scaling and becomes linear at high values of the ratio of the field and the temperature, indicating that the strange-metal regime extends well beyond p*. Moreover, the magnitude of the magnetoresistance is found to be much larger than predicted by conventional theory and is insensitive to both impurity scattering and magnetic field orientation. These observations, coupled with analysis of the zero-field and Hall resistivities, suggest that despite having a single band, the cuprate strange-metal region hosts two charge sectors, one containing coherent quasiparticles, the other scale-invariant 'Planckian' dissipators.

Sarcopenic obesity is associated with a faster decline in renal function in people with type 2 diabetes.

AIM: To evaluate the association between sarcopenic obesity and the decline in estimated GFR in people with type 2 diabetes. METHODS: We enrolled 745 people with type 2 diabetes (mean age 64.6 years, 53.6% men). Body composition was evaluated using dual-energy X-ray absorptiometry. Skeletal muscle index, calculated as appendicular non-fat mass (kg) divided by height squared (m2 ), was used to determine sarcopenia. Sarcopenic obesity was defined as the coexistence of sarcopenia and a ratio of android to gynoid fat mass greater than the median values in each gender. The association of sarcopenic obesity both with the annual rate of decline in estimated GFR and a >30% decline in estimated GFR was evaluated using multivariate linear regression models and Cox proportional hazard models, respectively. RESULTS: Participants with sarcopenic obesity were at an increased risk of a high annual rate of decline in estimated GFR, even after adjustment for the confounding variables (standardized ß = -0.228, P <0.001). Sarcopenic obesity was also significantly associated with risk of a >30% decline in estimated GFR (hazard ratio 4.52, 95% CI 2.16-9.47; P < 0.01) in multivariate model. CONCLUSIONS: Sarcopenic obesity evaluated by dual energy X-ray absorptiometry is associated with a faster decline in renal function in people with type 2 diabetes.

Efficacy of discontinuing risedronate for patients with systemic lupus erythematosus: a prospective study.

Objective The objective of this study is to investigate the effectiveness of discontinuation of risedronate for patients with systemic lupus erythematosus (SLE) treated with glucocorticoid (GC). Methods The participants were patients with SLE treated with prednisolone (PSL) ≥ 2 mg/day and risedronate for at least three years. Lumbar spine and total hip bone mineral density (BMD) measurements were taken at baseline and 24 and 48 weeks after discontinuation of risedronate, and bone turnover markers were evaluated at baseline, 12, 24, 36, and 48 weeks. Results A total of 36 patients were enrolled, 25 of whom discontinued risedronate. The mean age was 46.8 ± 11.2 years, and 23 were female. The mean duration of GC treatment was 14.8 ± 11.4 years, the mean dose of PSL was 7.8 ± 3.9 mg/day, and the mean duration of risedronate was 5.8 ± 2.4 years. Seventeen patients showed decreased lumbar spine BMD at 48 weeks after discontinuation of risedronate, with a mean lumbar spine lumbar decrease of 1.42% ± 3.20% ( p = 0.034); 17 patients (71%) showed a decreased total hip BMD at 48 weeks after discontinuation of risedronate, with a mean total hip BMD decrease of 0.99% ± 2.10% ( p = 0.021). Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) ≥ 309 mU/dl at baseline was a risk factor for decreased total hip BMD at 48 weeks compared with serum TRACP-5b < 309 mU/dl (56% vs 0%, p = 0.0098). One patient developed a clinical fracture of the lumbar spine at 20 weeks. Conclusions Discontinuation of risedronate treatment in patients with SLE who had received GC therapy led to decreases in lumbar spine and total hip BMD, particularly in patients with high baseline serum TRACP-5b levels.

Changes in the blood level, efficacy, and safety of tacrolimus in pregnancy and the lactation period in patients with systemic lupus erythematosus.

OBJECTIVES: We investigated the efficacy and safety of tacrolimus (TAC) by monitoring its serum concentration for mothers and infants in pregnant patients with systemic lupus erythematosus (SLE). METHODS: We measured trough concentrations of TAC in 25 pregnant patients with SLE to assess influence of TAC on the disease activity. Additionally, we measured the concentrations of TAC in umbilical arterial blood, breast milk, and breastfed infants to investigate the safety of TAC for the mothers and infants. RESULTS: The trough concentrations of TAC in the mothers significantly decreased in the second trimester as compared with those before pregnancy. However, the decrease in the trough concentrations of TAC did not lead to the deterioration of SLE. When examined, the doses of TAC were significantly lower in the second trimester and postpartum in the deteriorating group than those in the non-deteriorating group. There were no adverse events by TAC in mothers and fetuses. The concentrations of TAC in the umbilical cord blood were lower than those in the maternal blood. The relative infant dose in breastfed infants of TAC was < 1%. The level of TAC in infant bloods was below detectable limits. CONCLUSION: These findings suggest that TAC is one of the most effective and safest immunosuppressive drugs for use in pregnant patients with SLE.

Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheumatoid arthritis.

OBJECTIVE: To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors. METHOD: This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years. RESULTS: ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies. CONCLUSIONS: Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.

Proteinuria selectivity index as a prognostic biomarker in lupus nephritis.

Objectives The selectivity index has been proposed in predicting the response to immunosuppressive therapy in nephrotic syndrome and other primary kidney disorders. The aim of this study was to elucidate the predictive value of the selectivity index for the treatment response and renal outcome in patients with lupus nephritis. Methods Forty-four patients with lupus nephritis with selectivity index available at the time of renal biopsy were divided into two groups according to the cut-off value of the selectivity index determined by a receiver operating characteristics curve to differentiate treatment responders from non-responders. The baseline characteristics, overall response rate and renal functional outcome were studied retrospectively, and compared between the two groups. Prognostic factors for achieving remission were identified. Results The cut-off value of the selectivity index was 0.167. The low selectivity index (<0.167) and the high selectivity index (≥0.167) group included 24 and 20 patients, respectively. The overall response rate was significantly higher (88% vs. 50%, P = 0.007) and the rate of progression to end-stage renal disease was lower in the low selectivity index group (0% vs. 15%, P = 0.049). More patients in the high selectivity index group had chronic lesions on renal biopsy ( P = 0.002). The selectivity index was the prognostic factor for achieving overall response based on a multivariate analysis ( P = 0.020). Conclusions A selectivity index ≥0.167 was a strong predictor for a poor treatment response and the presence of chronic lesions on renal biopsy. Further exploration with a larger cohort and longer follow-up period is warranted.

Occurrence of human respiratory syncytial virus in summer in Japan.

In temperate zones, human respiratory syncytial virus (HRSV) outbreaks typically occur in cold weather, i.e. in late autumn and winter. However, recent outbreaks in Japan have tended to start during summer and autumn. This study examined associations of meteorological conditions with the numbers of HRSV cases reported in summer in Japan. Using data from the HRSV national surveillance system and national meteorological data for summer during the period 2007-2014, we utilized negative binomial logistic regression analysis to identify associations between meteorological conditions and reported cases of HRSV. HRSV cases increased when summer temperatures rose and when relative humidity increased. Consideration of the interaction term temperature × relative humidity enabled us to show synergistic effects of high temperature with HRSV occurrence. In particular, HRSV cases synergistically increased when relative humidity increased while the temperature was ⩾28·2 °C. Seasonal-trend decomposition analysis using the HRSV national surveillance data divided by 11 climate divisions showed that summer HRSV cases occurred in South Japan (Okinawa Island), Kyushu, and Nankai climate divisions, which are located in southwest Japan. Higher temperature and higher relative humidity were necessary conditions for HRSV occurrence in summer in Japan. Paediatricians in temperate zones should be mindful of possible HRSV cases in summer, when suitable conditions are present.

The Relationship between Psychotropic Drug Use and Suicidal Behavior in Japan: Japanese Adverse Drug Event Report.

Introduction: Very few studies have explored the adverse effect of psychotropic drugs worldwide. Methods: This study analyzed 1 813 suicide-related drug reports involving 553 patients collected from the Japanese National Adverse Drug Report Database between October 2001 and January 2012 to investigate psychotropic drugs associated with completed suicide vs. other suicide-related behaviors, including ideation and self-injury. The drugs investigated included antidepressants, antipsychotics, benzodiazepines, non-benzodiazepine hypnotic agents, noradrenergic and specific serotonergic antidepressants, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and other drugs. Results: These reports referenced 300 (54.2%) individuals who completed suicide. Adjusting for age, sex, and drugs used, the multivariate model revealed that participants who took antipsychotics were 1.70 times (95% CI, 1.11-2.61) more likely to complete suicide compared with those who did not. All other drugs became non-significant. Compared with those who took only one medication, those prescribed more than 4 drugs were more likely to complete suicide (OR 4.44, 95% CI, 2.40-8.20). Discussion: Antipsychotic drugs and polypharmacy may be regarded as predictors of completed suicide.

Suppression of infliximab antibody levels by azathioprine in patients with rheumatoid arthritis.

In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enrolled a total of 10 Japanese adult patients with RA who were treated with infliximab concomitantly with methotrexate or azathioprine. Serum concentrations of infliximab and ATI of these patients were measured. The mean serum infliximab concentrations was 1.6±1.3 µg/ml in patients with methotrexate and 1.0±0.5 µg/ml in patients with azathioprine. Serum ATI concentrations were below the limit of quantitation in 4 of 5 patients in each group. The results from the present study suggest that azathioprine suppresses ATI production.

Effect of genetic polymorphisms of azathioprine-metabolizing enzymes on response to rheumatoid arthritis treatment.

Azathioprine (AZA) is increasingly being prescribed to rheumatoid arthritis (RA) patients. Following oral administration, AZA is converted into its active form. Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) patients with low thiopurine (S)-methyltransferase (TPMT) activity tend to respond well to AZA therapy. In a previous study of Japanese SLE patients under low-dose AZA therapy, the group with the 94C>A mutation in inosine triphosphatase (ITPA) showed greater improvement in their disease activity index. However, it is not yet clear how genotypes relate to responsiveness to RA treatment. The genotypes ITPA 94C>A, TPMT*3C, NUDT15 595C>T, GST-M1, GST-T1 and MRP4/ABCC4 2269G>A of Japanese patients with RA were determined. The relationship between these genotypes and response to AZA therapy was evaluated using the Disease Activity Score 28 (DAS28) and various medical data. Of the 22 patients 15 had the ITPA 94C/C genotype, 7 had the ITPA 94C/A genotype, none had the TPMT*3C mutation, 4 had the NUDT15 595C>T mutation, 8 had the GST-M1 and T1 null genotypes and 9 had the MRP4/ABCC4 2269G>A mutation. Changes in DAS28 at 6 months after baseline were similar in both ITPA genotype groups. However, the maintenance dose of AZA was significantly lower in the C/A group than in the C/C group (0.85±0.30 mg/kg/day vs. 1.2±0.46 mg/kg/day, respectively; p = 0.043). The ITPA 94C/A group showed the same response to RA treatment as the C/C group, but at a lower dose. This demonstrates that RA patients with the ITPA 94C>A mutation are more responsive to AZA.

Anti-signal recognition particle antibody in patients without inflammatory myopathy: a survey of 6180 patients with connective tissue diseases.

OBJECTIVES: To clarify the prevalence of anti-signal recognition particle (anti-SRP) antibody in connective tissue diseases (CTDs) and investigate the clinical characteristics of patients without inflammatory myopathy. METHOD: Sera from 6180 patients with CTD were examined by immunoprecipitation (IPP) assays, and the records of patients positive for anti-SRP antibody were reviewed retrospectively. The antibody against the 54-kDa protein of SRP (SRP54) was quantified by enzyme-linked immunosorbent assay (ELISA) in patients with anti-SRP antibody. RESULTS: Of the 28 patients positive for anti-SRP antibody, nine (32.1%) did not have inflammatory myopathy. The clinical diagnoses and characteristics of those patients varied considerably. In patients with inflammatory myopathy, the index of anti-SRP54 was much higher than in those without myopathy (1.15 vs. 0.46; p = 0.036). CONCLUSIONS: The prevalence of anti-SRP antibody was 0.5% in a cohort of Japanese patients with CTD, and one-third of them did not have inflammatory myopathy. Sera from patients with inflammatory myopathy recognized SRP54 more strongly than in those without myopathy.

Overexpression of CXCR4 on circulating B cells in patients with active systemic lupus erythematosus.

OBJECTIVES: To evaluate the roles of circulating B cells in the pathogenic process of systemic lupus erythematosus (SLE) by measuring the expression of chemokines and their receptors. METHODS: Peripheral-blood mononuclear cells were obtained from 17 active, 21 inactive SLE patients, and 13 healthy controls. The expression of CXCR4, CXCR5, and CCR7 on CD19+ B cells was determined by flow cytometry, serum concentration of CXCL12 was measured by enzyme-linked immunosorbent assay, and the chemotactic responsiveness of B cells toward CXCL12 was evaluated. B or plasma cells expressing CXCR4 in renal biopsy specimens were detected using immnofluorescent staining. RESULTS: Flow cytometric analysis revealed that expression level of CXCR4 on circulating B cells was significantly higher in patients with active disease than in those with inactive disease or controls. Serum CXCL12 concentration was not different between these groups. In addition, the migratory ability of B cells toward CXCL12 was enhanced in active SLE patients. Finally, CXCR4-expressing B cells were more frequently observed in the renal biopsy specimens of lupus nephritis. CONCLUSIONS: Up-regulated CXCR4 expression on circulating B cells in active SLE may enhance their chemotactic response toward CXCL12, which may promote infiltration of these cells into inflamed renal tissue and contribute to the development of SLE.

RISING beamline (BL28XU) for rechargeable battery analysis.

The newly installed BL28XU beamline at SPring-8 is dedicated to in situ structural and electronic analysis of rechargeable batteries. It supports the time range (1 ms to 100 s) and spatial range (1 µm to 1 mm) needed for battery analysis. Electrochemical apparatus for battery charging and discharging are available in experimental hutches and in a preparation room. Battery analysis can be carried out efficiently and effectively using X-ray diffraction, X-ray absorption fine-structure analysis and hard X-ray photoelectron spectroscopy. Here, the design and performance of the beamline are described, and preliminary results are presented.

A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti-TNF treatment in Japanese patients with rheumatoid arthritis.

OBJECTIVES: Recent genome-wide association studies disclosed that several single nucleotide polymorphisms (SNPs), including tumour necrosis factor (TNF) receptor-associated factor 1 (TRAF1) (+16860A/G), are associated with the pathophysiology of rheumatoid arthritis (RA). We assessed the usefulness of TRAF1 genotyping as a genetic predictor of the response to anti-TNF treatment in Japanese RA patients. METHODS: TRAF1 (+16860A/G) was genotyped using the TaqMan SNP genotyping assay in 101 Japanese RA patients treated with anti-TNF drugs for >24 weeks. We retrospectively analysed the association between SNP and the clinical response to treatment. TRAF1 mRNA and protein expression was also evaluated in CD4+, CD8+, CD14+, or CD19+ cells from 25 healthy subjects using quantitative polymerase chain reaction and intracellular staining flow cytometry, respectively. RESULTS: No statistical difference in DAS28-ESR at baseline was observed between the patient groups with the AA, AG, or GG genotype. The GG genotype was more frequent in non-responders than in good or moderate responders [odds ratio (OR) 7.4, 95% confidence interval (CI) 1.5-37.5]. The non-responders possessed the G allele more frequently than the good or moderate responders (OR 3.5, 95% CI 1.4-9.0). TRAF1 protein expression increased significantly in CD14+ monocytes from healthy subjects with the GG genotype compared with that in subjects with the AA or AG genotype. CONCLUSIONS: TRAF1 (+16860A/G) may be useful for predicting the clinical response to anti-TNF treatment and may contribute to resistance to treatment in RA patients with the GG genotype by increasing the TRAF1 expression in circulating inflammatory cells.

Momentum-dependent scaling exponents of nodal self-energies measured in strange metal cuprates and modelled using semi-holography.

The anomalous strange metal phase found in high-Tc cuprates does not follow the conventional condensed-matter principles enshrined in the Fermi liquid and presents a great challenge for theory. Highly precise experimental determination of the electronic self-energy can provide a test bed for theoretical models of strange metals, and angle-resolved photoemission can provide this as a function of frequency, momentum, temperature and doping. Here we show that constant energy cuts through the nodal spectral function in (Pb,Bi)2Sr2-xLaxCuO6+δ have a non-Lorentzian lineshape, consistent with a self-energy that is k dependent. This provides a new test for aspiring theories. Here we show that the experimental data are captured remarkably well by a power law with a k-dependent scaling exponent smoothly evolving with doping, a description that emerges naturally from anti-de Sitter/conformal-field-theory based semi-holography. This puts a spotlight on holographic methods for the quantitative modelling of strongly interacting quantum materials like the cuprate strange metals.

ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease.

Functional single-nucleotide polymorphisms (SNPs) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) (rs28493229) and caspase-3 (CASP3) (rs113420705; formerly rs72689236) are associated with susceptibility to Kawasaki's disease (KD). To evaluate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG) unresponsiveness, we investigated 204 Japanese KD patients who received a single IVIG dose of 2 g kg(-1) (n=70) or 1 g kg(-1) daily for 2 days (n=134). The susceptibility allele of both SNPs showed a trend of overrepresentation in IVIG non-responders and, in combined analysis of these SNPs, patients with at least 1 susceptible allele at both loci had a higher risk for IVIG unresponsiveness (P=0.0014). In 335 prospectively collected KD patients who were treated with IVIG (2 g kg(-1)), this 2-locus model showed a more significant association with resistance to initial and additional IVIG (P=0.011) compared with individual SNPs. We observed a significant association when all KD patients with coronary artery lesions were analyzed with the 2-locus model (P=0.0031). Our findings strongly suggest the existence of genetic factors affecting patients' responses to treatment and the risk for cardiac complications, and provide clues toward understanding the pathophysiology of KD inflammation.

Scanning tunnelling microscopy imaging of symmetry-breaking structural distortion in the bismuth-based cuprate superconductors.

A complicating factor in unravelling the theory of high-temperature (high-T(c)) superconductivity is the presence of a 'pseudogap' in the density of states, the origin of which has been debated since its discovery. Some believe the pseudogap is a broken symmetry state distinct from superconductivity, whereas others believe it arises from short-range correlations without symmetry breaking. A number of broken symmetries have been imaged and identified with the pseudogap state, but it remains crucial to disentangle any electronic symmetry breaking from the pre-existing structural symmetry of the crystal. We use scanning tunnelling microscopy to observe an orthorhombic structural distortion across the cuprate superconducting Bi(2)Sr(2)Ca(n-1)Cu(n)O(2n+4+x) (BSCCO) family tree, which breaks two-dimensional inversion symmetry in the surface BiO layer. Although this inversion-symmetry-breaking structure can impact electronic measurements, we show from its insensitivity to temperature, magnetic field and doping, that it cannot be the long-sought pseudogap state. To detect this picometre-scale variation in lattice structure, we have implemented a new algorithm that will serve as a powerful tool in the search for broken symmetry electronic states in cuprates, as well as in other materials.

Effects of interocclusal distance on bite force and masseter EMG in healthy participants.

The aim of this study was to investigate effects of interocclusal distance (IOD) on bite force and masseter electromyographic (EMG) activity during different isometric contraction tasks. Thirty-one healthy participants (14 women and 17 men, 21·2 ± 1·8 years) were recruited. Maximal Voluntary Occlusal Bite Force (MVOBF) between the first molars and masseter EMG activity during all the isometric-biting tasks were measured. The participants were asked to bite at submaximal levels of 20%, 40%, 60% and 80% MVOBF with the use of visual feedback. The thickness of the force transducer was set at 8, 12, 16 and 20 mm (= IOD), and sides were tested in random sequence. MVOBF was significantly higher at 8 mm compared with all other IODs (P < 0·001). Only in women, IOD always had significant influence on the corresponding root-mean-square (RMS) value of EMG (P < 0·011). When biting was performed on the ipsilateral side to the dominant hand, the working side consistently showed higher masseter EMG activity compared with the balancing side (P < 0·020). On the contralateral side, there was no difference between the masseter EMG at any IODs. The results replicated the finding that higher occlusal forces can be generated between the first molars at shorter IODs. The new finding in this study was that an effect of hand dominance could be found on masseter muscle activity during isometric biting. This may suggest that there can be a general dominant side effect on human jaw muscles possibly reflecting differences in motor unit recruitment strategies.

Characteristics and outcome of suspected cerebrovascular disease in dogs: 66 cases (2009-2016).

OBJECTIVES: To characterise the clinical signs of suspected cerebrovascular disease in dogs. MATERIALS AND METHODS: Medical records of one hospital were searched from November 2009 to December 2016 for dogs that suffered of cerebrovascular disease. We diagnosed cerebrovascular disease based on acute onset, clinical signs and magnetic resonance imaging findings. The medical history, clinical signs, concurrent disease, area of infarction, cerebrospinal fluid results, month at onset and outcome were investigated in the cerebrovascular disease group and in a control group (dogs with brain disorders other than cerebrovascular disease). RESULTS: A total of 122 CVD cases were extracted from the 5312 patients that visited during the study period. Of these 122 cases, 66 (1.2%) matched the subject selection criteria of our study and were included in the analysis. Forebrain infarction was observed in 51 of 66 cases, of which 24 (47.1%) suffered from seizures. The number of dogs diagnosed with cerebrovascular disease was disproportionately high in August (nine of 59 cases) and December (13 of 59 cases). In the outcome survey, deterioration was observed in 11 of 55 cases. CLINICAL SIGNIFICANCE: Seizure is an important clinical sign of cerebrovascular disease in dogs. There was a significant seasonal variation in the number of dogs diagnosed with cerebrovascular disease in Japan. Clinical features observed in this report differ from those of previous reports and highlight the need for additional research in this area.