The damage to river engineering structures induced by large‐wood (LW) jams is one of the significant problems in river management. For example, typical bridge damage in alluvial areas in Japan, such ...as wash away, is often caused by the accumulation of large wood materials. The densely transported large wood pieces are an important factor in the accumulation process. We investigated the influence of local flows generated by hydraulic structures on the initial stage of the concentration of large wood pieces. First, we experimentally investigated the flow structures generated by spur dikes in a 0.6 m wide channel and the trajectory of large wood pieces. Then, we numerically investigated the influence of external force on the transport mechanisms of large wood pieces. We employed a simplified Basset‐Boussinesq‐Oseen model to evaluate each term of the momentum equation of the particles and calculated the trajectories of the wood pieces previously observed experimentally. The results showed that the transported large wood pieces were concentrated in low‐vorticity regions of the water surface. This tendency was more prevalent in short pieces (10 mm) than in long pieces (40 mm) because the influence of the relatively small‐scale patterns of the pressure gradient of the surrounding water surface might be spatially averaged for long pieces. This tendency has not been explicitly elucidated in previous works; thus, this knowledge is expected to be key in controlling LW transport, such as detecting the possible regions where LW jams occur or designing efficient inlet sections of LW retention facilities.
Plain Language Summary
The damage to river engineering structures caused by large wood pieces is a significant problem throughout the world. For example, in Japan, bridge damage due to large wood in alluvial areas is typically caused by the accumulation of the large wood transported through channels. Thus, it is necessary to investigate the mechanism of how the river flow contributes to the accumulation of large wood pieces. For this purpose, the flow velocity and the trajectory of large wood pieces in a flume experiment were precisely observed using image analysis methods. Then, a particle‐based model of large wood pieces was developed, and the mechanism of how the flow field influences the movement of large wood pieces was investigated. The results revealed that the small‐scale patterns of the pressure gradient of the surrounding water surface play an important role in the concentration mechanism. This tendency has not been explicitly elucidated, and therefore, this knowledge is expected to be key in controlling large‐wood transport in the river engineering field.
Key Points
The velocity field and the trajectory of large wood pieces in a flume experiment were precisely observed using image analysis methods
A particle‐based model of a large wood piece was developed, which could reproduce the trajectories of large wood pieces in a flow field
The pressure gradient of the water surrounding large wood pieces plays a dominant role in the wood piece dynamics
Although it is known that human leukocyte antigen (HLA)-DPB1 disparity has a strong impact on outcomes in unrelated hematopoietic transplantation with induction of acute graft-versus-host disease ...(GVHD) and a graft-versus-leukemia (GVL) effect, its role in unrelated umbilical cord blood transplantation (UR-CBT) has yet to be fully clarified. Our current study is being conducted to elucidate the impact of HLA-DPB1 mismatch, along with the effect of other HLA loci mismatches at the allele level. HLA six loci alleles were retrospectively typed in 1157 Japanese donors and patients with leukemia or myelodysplastic syndrome who underwent transplantation with a single unit of cord blood. HLA-DPB1 mismatch was associated with a significant reduction in leukemia relapse (hazard ratio 0.61, P<0.001), whereas the other HLA loci allele-level mismatches did not. No significant effect of HLA-DPB1 mismatch was observed in the risk of acute GVHD, engraftment or mortality. This HLA-DPB1 GVL effect without induction of severe acute GVHD or deterioration of survival rate has not been reported in unrelated bone marrow or peripheral blood stem cell transplantations, suggesting apparent advantages of UR-CBT. Accordingly, selection of an HLA-DPB1 mismatch cord blood might be the preferable choice for single-unit UR-CBT.
The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of ...children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation 88% (95% confidence interval: 86-90) versus 92% (90-94), failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation 56% (54-59) versus 87% (85-90); P<0.0001. There was no significant improvement in outcomes over the two time periods (1992-1999 versus 2000-2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia.
This retrospective study was conducted in Japan to determine the incidence, risk factors and outcomes of sinusoidal obstruction syndrome (SOS) after allogeneic hematopoietic stem cell transplantation ...(HSCT). Among 4290 patients undergoing allogeneic HSCT between 1999 and 2010, 462 were diagnosed with SOS according to the Seattle criteria (cumulative incidence, 10.8%). The cumulative incidence of SOS diagnosed by the modified Seattle criteria was 9.3%. Of 462 patients, 107 met the Baltimore criteria and 168 had severe SOS with renal and/or respiratory failure. The median onset for SOS was 12 days after HSCT (range, -2-30). Overall survival at day 100 was 32% for SOS and 15% for severe SOS. Multivariate analyses showed that significant independent risk factors for SOS were the number of HSCTs, age, performance status, hepatitis C virus-seropositivity, advanced disease status and myeloablative regimen. SOS was highly associated with overall mortality (hazard ratio, 2.09; P<0.001). Our retrospective survey showed that the cumulative incidence of SOS in Japan was 10.8%, similar to that previously reported in Western countries, and that the overall survival of patients who developed SOS was low. Furthermore, several risk factors were identified. Preventive and therapeutic strategies for high-risk SOS patients must be established to improve overall survival.
Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized with chromosomal instability and a high propensity to myeloid malignancy. Although causative genes have been identified ...in most patients, the genetic background of the leukemic transformation in FA has not been fully understood.
We studied 2 acute myeloid leukemia (AML) and 7 myelodysplastic syndromes (MDS) developed in patients with FA using whole-genome sequencing and analyzed somatic mutations, structural variants and copy number alterations.
The number of somatic mutations and copy number alterations (CNAs) in AML were 1,071 mutations and 4 CNAs per patient on average, which tended to be higher than those in MDS (265 mutations and 2.3 CNAs per patient). For mutational signatures, three known signatures were identified, which included SBS1 and SBS5 caused by endogenous mutational processes, and SBS3 related to defective homologous recombination. Mutations and structural variants affected known driver genes in myeloid malignancies, such as RUNX1 (n = 3), ASXL1 (n = 1), CBL (n = 1), NRAS (n = 1) and KDM6A (n = 1). Recurrent copy number alterations were more frequently detected, including +3q (n = 6), +1q (n = 4) and -7q (n = 2). The majority of these CNAs were clonal and all but one patient harbored either of +3q or +1q, indicating the early acquisition of copy number changes and their driver role in leukemic transformation.
Myeloid neoplasms related with FA were characterized by a unique pattern of CNAs and common driver mutations in myeloid malignancies.
Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal ...hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972.
Disaster evacuation increases the risk of becoming overweight or obese owing to lifestyle changes and psychosocial factors. This study evaluated the effect of evacuation on becoming overweight during ...a 7-year follow-up among residents of Fukushima Prefecture during the Great East Japan Earthquake.
This was a prospective cohort study.
We analysed data collected from 18,977 non-overweight Japanese participants who completed the ‘Comprehensive Health Checkup Program’ and ‘Mental Health and Lifestyle Survey’, as part of the Fukushima Health Management Survey, between July 2011 and November 2012. An evacuation was defined as the moving out of residents of municipalities designated as an evacuation zone by the government or having a self-reported experience of moving into shelters or temporary housing. Follow-up examinations were conducted in March 2018 to identify patients who became overweight. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using a Cox proportional hazards regression model.
Among 15,875 participants (6091 men and 9784 women; mean age 63.0 ± 11.1 years) who received follow-up examination (mean follow-up, 4.29 years), 2042 (856 men and 1186 women) became overweight. Age-, baseline body mass index-, lifestyle-, and psychosocial status–adjusted HRs (95% CIs) for becoming overweight after evacuation were 1.44 (1.24–1.66) for men and 1.66 (1.47–1.89) for women.
Evacuation was associated with the risk of becoming overweight 7 years after the disaster. Thus, maintaining physical activity, healthy diet, and sleep quality and removing barriers to healthy behaviour caused by disasters, including anxiety concerning radiation, may prevent this health risk among evacuees.
BackgroundLung diseases, such as airway disease and interstitial lung disease (ILD), are often complicated in patients with rheumatoid arthritis (RA). The presence of those pre-existing lung diseases ...is one of the poor prognostic factors and risk factors for infectious pneumonia in patients with RA. There have been several concerned issues regarding pulmonary complications in RA patients with pre-existing lung diseases during treatment with disease-modifying antirheumatic drugs (DMARDs) because of infectious pneumonia or acute exacerbation in ILD, occasionally resulting in fatal outcome.ObjectivesWe identified risk factors for serious pulmonary complications in patients with pre-existing lung disease during treatment with DMARDs in RA.MethodsThis study enrolled consecutive 487 RA patients at our hospital from 2005 to 2016 retrospectively. 110 of those 487 patients had pre-existing lung disease at the first visit to our hospital. At first, we divided those 110 patients into two subsets, one with development of serious pulmonary complication and the other without that during observational periods. We defined hospitalisation due to lung disease as a serious pulmonary complication regardless of the causes. Demographic and clinical data at enrollment as well as treatment regimens were collected by review of medical charts. We conducted a univariate analysis to compare the differences of clinical characteristics between the subsets. In multivariate analysis, the Cox proportional hazard model was employed to identify factors independently associated with serious pulmonary complication. The explanatory variables were chosen based on candidates (p<0.25) identified by the univariate analysis. In addition, we focused on 42 RA patients during treatment with biological DMARD (bDMARD), and identified their risk factors by the same procedure mentioned above.ResultsIn 110 RA patients with pre-existing lung disease, the median age and disease duration at enrollment was 70 and 3 years, and 71% were female. Rheumatoid factor and anti-cyclic citrullinated protein antibody (anti-CCP) were detected in 97 (88%) and 95 (86%) patients. Methotrexate (MTX), sulfasalazine (SSZ), bDMARDs and corticosteroid were prescribed in 37 (34%), 48 (44%), 42 (38%) and 65 (59%) patients. During the median observation periods of 11 months, 17 (15%) patients had serious pulmonary complications due to pulmonary infection in 11, exacerbation of ILD in 5, and drug-induced pneumonia in 1. The univariate analysis identified candidate variables for serious pulmonary complications as follows: use of MTX and bDMARDs, and no use of SSZ. In multivariate analysis, use of bDMARDs (HR 2.9, 95% CI 0.99–9.0; p=0.05) was identified as the independent risk factor. In 42 patients during treatment with bDMARDs, the univariate analysis identified candidate variables as follows: elder age, male, higher levels of anti-CCP, use of MTX, and no use of SSZ. In multivariate analysis, the higher levels of anti-CCP (HR 1.002, 95% CI 1.0003–1.004; p=0.0007) and no use of SSZ (HR 441.8, 95% CI 1.1–4658460.2; p=0.04) were identified as the independent risk factors.ConclusionsSerious pulmonary complications should be more careful for RA patients with pre-existing lung disease during treatment with bDMARDs, particularly those with higher levels of anti-CCP or no use of SSZ.Disclosure of InterestNone declared
Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we ...evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5-16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41-69%) and 97% (95%CI: 87-99%), respectively. Median telomere length in responders was -0.4 standard deviation (SD) (-2.7 to +3.0 SD) and -1.5 SD (-4.0 to +1.6 (SD)) in non-responders (P<0.001). Multivariate analysis showed that telomere length shorter than -1.0 SD (hazard ratio (HR): 22.0; 95%CI: 4.19-115; P<0.001), platelet count at diagnosis less than 25×10(9)/L (HR: 13.9; 95%CI: 2.00-96.1; P=0.008), and interval from diagnosis to immunosuppressive therapy longer than 25 days (HR: 4.81; 95%CI: 1.15-20.1; P=0.031) were the significant variables for poor response to immunosuppressive therapy. Conversely to what has been found in adult patients, measurement of the telomere length of lymphocytes at diagnosis is a promising assay in predicting the response to immunosuppressive therapy in children with aplastic anemia.
PDF
