First-line Combination Strategy Provides Favorable 5-year Outcomes for Patients with Lupus Nephritis: A Single-center Observational Study

This observational study aimed to clarify the long-term results of the combination of mizoribine (MZB), tacrolimus (TAC) and prednisolone as first-line therapy for lupus nephritis (LN). This was our institution’s standard therapy between 2009 and 2015, when we saw 36 patients with LN. When a patient thus treated achieved SLEDAI remission (= 0) and/or the prednisolone dose could be tapered to 5 mg/day, either MZB or TAC was stopped, and the other was continued for maintenance therapy. If treatment failure or relapse occurred, second-line therapy was introduced. At years 1 and 5, overall complete renal response and SLEDAI remission were 94% and 88%, and 50% and 62%, respectively. Excluding 2 cases lost to follow-up, medications after 5 years were as follows: 20 (59%) were stable on 1 drug (MZB or TAC), 11 (32%) required continuation of both drugs (MZB + TAC), and 3 (9%) required second-line therapy. The 5-year retention rate was 91% (non-secondline), with 0% of relapse in this group. Our first-line combination strategy showed high remission rates in the induction phase, and subsequent maintenance therapy demonstrated good outcomes for up to 5 years. Research that fine-tunes the order of therapeutic agents and institutes appropriate treatment goals may further improve long-term outcomes for patients with LN

Mixing analysis of groundwater recharge sources for better watershed management

This paper describes application of three-end member mixing model with isotopic tracers to analyse groundwater recharge sources in the Nasu Fan, Japan. Relative contribution of river water accounts for 50-60% at areas adjacent to interrupted rivers, and precipitation fallen onto the fan is dominant recharge source at the other areas. Contribution ratio of paddyfield water is 30% at most. Implication of such results for better watershed management is given

Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial.

ObjectiveTo evaluate the efficacy of denosumab in suppressing joint destruction when added to conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy in patients with rheumatoid arthritis (RA).MethodsThis was a multi-centre, randomised, double-blind, parallel-group, placebo-controlled phase 3 study in Japan. Patients with RA aged ≥20 years receiving csDMARDs were randomly assigned (1:1:1) to denosumab 60 mg every 3 months (Q3M), denosumab 60 mg every 6 months (Q6M) or placebo. The change in the modified total Sharp score (mTSS) and effect on bone mineral density (BMD) at 12 months was evaluated.ResultsIn total, 654 patients received the trial drugs. Denosumab groups showed significantly less progression of joint destruction. The mean changes in the mTSS at 12 months were 1.49 (95% CI 0.99 to 1.99) in the placebo group, 0.99 (95% CI 0.49 to 1.49) in the Q6M group (p=0.0235) and 0.72 (95% CI 0.41 to 1.03) in the Q3M group (p=0.0055). The mean changes in bone erosion score were 0.98 (95% CI 0.65 to 1.31) in the placebo group, 0.51 (95% CI 0.22 to 0.80) in the Q6M group (p=0.0104) and 0.22 (95% CI 0.09 to 0.34) in the Q3M group (p=0.0001). No significant between-group difference was observed in the joint space narrowing score. The per cent change in lumbar spine (L1-L4) BMD in the placebo, Q6M and Q3M groups were -1.03%, 3.99% (p<0.0001) and 4.88% (p<0.0001). No major differences were observed among safety profiles.ConclusionsDenosumab inhibits the progression of joint destruction, increases BMD and is well tolerated in patients with RA taking csDMARD

A preliminary analysis of the formation of travertine and travertine cones in the Jifei hot spring, Yunnan, China

The Jifei hot spring emerges in the form of a spring group in the Tibet–Yunnan geothermal zone, southwest of Yunnan Province, China. The temperatures of spring waters range from 35 to 81°C and are mainly of HCO3–Na·Ca type. The total discharge of the hot spring is about 10 L/s. The spring is characterized by its huge travertine terrace with an area of about 4,000 m2 and as many as 18 travertine cones of different sizes. The tallest travertine cone is as high as 7.1 m. The travertine formation and evolution can be divided into three periods: travertine terrace deposition period, travertine cone formation period and death period. The hydrochemical characteristics of the Jifei hot spring was analyzed and compared with a local non-travertine hot spring and six other famous travertine springs. The results indicate that the necessary hydrochemical conditions of travertine and travertine cones deposition in the Jifei area are (1) high concentration of HCO3 − and CO2; (2) about 52.9% deep source CO2 with significantly high PCO2 value; (3) very high milliequivalent percentage of HCO3 − (97.4%) with not very high milliequivalent percentage of Ca2+ (24.4%); and (4) a large saturation index of calcite and aragonite of the hot water

Regional Assessment of Recharge Elevation of Tap Water Sources Using the Isoscape Approach

The importance of mountains as “natural water towers” has been quantified by comparing water budgets in upstream (mountain) and downstream (lowland) areas, but their importance for tap water supplies has not been assessed. Here, we propose an isoscape approach to estimate the mean recharge elevation of tap water sources (rivers, reservoirs, springs, and wells) and apply it to a region in central Japan as a case study. Errors in the estimation of mean recharge elevation were estimated at 90–140 m. Results show that mean recharge elevations for about 90% of sources in the region are at 1000 m above sea level or higher. A little over half of the land area is above that elevation, while 98% of the population lives below it. These findings indicate that tap water disproportionally depends on recharge in mountains and is disproportionately supplied to lowland residents. Higher locations of spring water sources and longer (vertical) distances of groundwater flow for well water sources make the recharge-to-population disproportionality more remarkable. Furthermore, our results suggest that larger cities require higher natural water towers to meet greater water demand, complemented by intermunicipal water suppliers. Some low-elevation municipalities depend heavily on water recharged in mountains well outside their territories. The method proposed here helps clarify how people depend on water supplies from mountains, providing essential knowledge for integrated management of mountains and water resources

Mizoribine, tacrolimus, and corticosteroid combination therapy successfully induces remission in patients with lupus nephritis

Conventional cyclophosphamide-based treatment regimens for lupus nephritis (LN) are still not considered to be optimal. The aim of this study was to evaluate the efficacy and safety of mizoribine, tacrolimus, and corticosteroid combination therapy for LN. We retrospectively evaluated a combination treatment of mizoribine and tacrolimus with corticosteroids as induction therapy in eight newly diagnosed systemic lupus erythematosus (SLE) patients with biopsy-proven LN. All patients were women, and their mean [standard deviation (SD)] age was 48.5 (20) years. All patients (100 %) had positive anti-double-stranded DNA (anti-dsDNA) antibody titers, and four (50.0 %) were nephrotic. Mean (SD) serum creatinine and daily proteinuria levels were 0.72 (0.4) mg/dl (range 0.33-1.55 mg/dl) and 4.56 (2.8) g (range 0.77-8.2 g), respectively. By month 2, significant improvements in the anti-dsDNA antibody titers, levels of proteinuria, serum albumin, and C3, and SLE disease activity index score were observed. By month 6, seven patients (87.5 %) were in complete remission, with normalized levels of both proteinuria and serum creatinine. This pilot study suggests that mizoribine and tacrolimus treatment with corticosteroids is well tolerated and may prove to be an optimal alternative remission-inducing regimen for LN

土壌水分変動とその大気へのインパクト : スリランカにおける事例

Time series analyses of soil moisture, rainfall, air temperature and other hydrometeorological components observed at inland area of Sri Lanka in 1994 were carried out. Auto-correlation analysis gives a time scale from 10 to 30 days as persistency of soil moisture anomaly, which is considerably small relative to that under midlatitude temperate climate and is shorter than that for atmospheric temperature. Two dominant periodicities are detected from spectral analysis : 45-60-day period (especially for large rainfall and soil moisture at all depths) and 22.5-30-day period (for small rainfall and shallow soil moisture). The two intraseasonal variations are also detected for satellite-remote-sensed outgoing longwave radiation (OLR) over and around Sri Lanka. Band-pass filtered OLR anomaly for the former periodicity propagates from around Sri Lanka to the west and is strengthened through the process of its westward propagation. On the other hand, OLR anomaly for the latter periodic component has its origin at east ocean-region and propagates westward to Sri Lanka. For the 45-60-day period, band-pass filtered anomaly propagates from rainfall to soil moisture, soil temperature, wet-bulb temperature and back to rainfall, indicating a feedback loop. In contrast, propagation of anomaly through hydrometeorological variables is not found for the 22.5-30-day period. These statistical results indicate that external forcing causes the latter periodic and also that the former periodicity is introduced by an enhancement of the latter variation once in its two cycles due to negative feedback between soil moisture and rainfall. The selective enhancement against different periodic variations appears to be associated with characteristic time-scale of the soil moisture persistence