Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Lectin-Tagged Fluorescent Polymeric Nanoparticles for Targeting of Sialic Acid on Living Cells

In this study, we fabricated lectin-tagged fluorescent polymeric nanoparticles approximately 35 nm in diameter using biocompatible polymers conjugated with lectins for the purpose of detecting sialic acid on a living cell surface, which is one of the most important biomarkers for cancer diagnosis. Through cellular experiments, we successfully detected sialic acid overexpression on cancerous cells with high specificity. These fluorescent polymeric nanoparticles can be useful as a potential bioimaging probe for detecting diseased cells

Prenatal diagnosis of short-rib polydactyly syndrome type 3 (Verma-Naumoff type) by three-dimensional helical computed tomography

We present a case of short-rib polydactyly syndrome (SRP) type 3 in which accurate prenatal diagnosis was feasible using both ultrasonography and 3D-CT. SRPs encompass a heterogeneous group of lethal skeletal dysplasias. However, the phenotypes overlap with those of nonlethal skeletal dysplasias, i.e., Ellis-van Creveld syndrome and Jeune syndrome. As accurate prenatal diagnosis of SRPs is helpful for parents, we used 3D-CT in the early third trimester to examine a fetus suggested to have phenotypes of "short-rib dysplasia group" on ultrasonography. 3D-CT showed mild modification of the vertebral bodies, small ilia with horizontal acetabula and triangular partial ossification defects, and subtle metaphyseal irregularities of the femora. These CT findings and an extensive literature search regarding the phenotypes of various diseases categorized as "short-rib dysplasia group" led to a correct prenatal diagnosis of SRP type 3. This case exemplified the usefulness of 3D-CT for the precise prenatal diagnosis of skeletal dysplasias

Presence of concurrent sarcoid-like granulomas indicate better survival in cancer patients

Introduction: An increased risk of sarcoidosis and sarcoid-like reactions in subjects with a history of malignancy has been suggested. We assessed the incidence and clinical characteristics of cancer patients with biopsies containing sarcoid-like granulomas on cancer metastasis and patient survival. Methods: This is a retrospective, multicenter, observational study involving patients who underwent Endobronchial Ultrasound (EBUS) at the University of Miami Hospital, Miami Veterans Affairs Medical Center in the USA and Chiba University in Japan. Subjects with a confirmed diagnosis of cancer and who subsequently developed granulomas in different organs were enrolled. The study was registered at Clinicaltrial.gov ( NCT03844698 ). Results: One hundred and thirty-three patients met the study criteria. The most common primary cancer sites were the skin (22.5%), breast (20.3%), and lymph node (LN) (12.8%). Twenty-four (18%) patients developed sarcoidal granulomas within 1 year of cancer diagnosis, 54(40.6%) between 1 and 5 years and 49(36.8%) after 5 years. Imaging showed possible sarcoidal granulomas in lymph nodes in 51 cases (38.3%) and lung tissue and mediastinal lymph nodes in 73 cases (54.9%); some parenchymal reticular opacity and fibrosis were found in 5(3.7%) and significant parenchymal fibrosis in 2(1.5%) subjects. According to logistic regression analysis, the frequency of metastatic cancer was significantly lower in patients with sarcoidal granulomas than in controls. Moreover, multivariate Cox proportional hazard analysis showed a significant survival advantage in those with sarcoidal granuloma. Conclusion: Sarcoidal granulomas are uncommon pathology findings in cancer patients. There is a significant association between the presence of granulomas and reduced metastasis and increased survival. Further study is warranted to understand the protective mechanism involved

Presence of concurrent sarcoid-like granulomas indicates better survival in cancer patients: a retrospective cohort study

These findings suggest that patients with underlying malignancy who develop sarcoidosis and sarcoid-like reactions have a lower risk of stage 4 metastatic disease and better survival compared to patients who do not develop such granulomatous reactions https://bit.ly/2CNhc9

The effect of friction stir processing on the microstructure and mechanical properties of an aluminum lithium alloy

The article of record as published may be found at http://dx.doi.org/10.1007/s11661-008-9698-8Friction stir processing (FSP) was conducted on a wrought plate of AA2099 to refine and homogenize the microstructure and enhance the through-thickness ductility and fracture resistance. Optical microscopy (OM), orientation imaging microscopy (OIM), and transmission electron microscopy (TEM) methods were employed to evaluate microstructure and micro- texture in as-received material and in material subjected to FSP as well as postprocessing heat treatments. Hardness and orientation-dependent tensile test data were combined with anticlastic bending fatigue data to characterize the as-received, processed, and processed and heat-treated conditions of the material.Defense Advanced Research Projects Agency (DARPA)Office of Naval Research (ONR)Contract no. N00014-06-WR-2-0196 (ONR

Wind damage at Ashoro Research Forest of Kyushu University caused by low pressure in October 2006

平成18年10月7日午後から8日午前中にかけて台風並みに発達し士低気圧により九州大学北海道演習林に大規模在風害が発生した。今後の資料とするため，ここではその被害概要についてまとめた。被害発生時，北海道演習林内では主に北ないし北北東方向から最大風速10m/s以上，瞬間最大風速20皿/.以上回風が吹いたと推定された。被害は北海道演習林のほぽ全域にわたり発生し，被害面積158ha，被害推定本数48,481本，被害推定材積21,284m^3に達した。今回の被害の特徴として，カラマツを中心とした針葉樹人工林，とくに40年生以上の壮齢林に大規模な風倒被害が発生したこと，被害が北東斜面の林分に集中し，風向とほぼ一致したこと，カラマツ林の被害形態は「根返り」が最も多く，次いで「傾斜・幹曲がり」で，「幹折れ」の被害はわずかであったこと等が挙げられた。This paper describes the investigation results of wind damage at Ashoro Research Forest, Kyushu University, Japan induced by heavy low pressure on October 7 and 8, 2006. When the low pressure was passing through Ashoro Research Forest, the estimated dominant wind direction was north or north-northeast, and the estimated maximum wind speed and the estimated maximum instantaneous wind speed were over 10 m/s and over 20m/s, respectively, based on the data from the four nearest AMeDAS (Automated Meteorological Data Acquisition System) observation points. The wind damage was scattered throughout Ashoro Research Forest. Total wind damage area, the estimated total number of damaged trees and their estimated total volume were 158 ha, 48,481 trees and 212,284m^3, respectively. The wind damage was observed in mainly artificial forests of Japanese larch. It was especially heacy in the matured forest stands (over 40 years old) and in the forest stands on the northeastern slope. Damage type of Japanese larch trees was mostly uprooting (75%), and the next largest type was leaning or bent (21%) and snapping was only 4%

Efficiency and cost of nuisance deer population control in Ashoro Research Forest.

北海道足寄町に位置する九州大学北海道演習林において実施されたシカ有害鳥獣捕獲の実施状況を明らかにし, 捕獲期間中に目撃されるシカの群れ構成数の動向と捕獲効率や費用との関係について検討した。捕獲期間中, 延べ従事人数は282人, 延べ従事時間は742時間の有害鳥獣捕獲が実施され, 420回の目撃機会があり, 1,711頭を目撃し, 192頭を捕獲した。目撃機会あたり捕獲できる頭数はほとんどの場合1頭であったことから, 目撃機会あたりの群れ構成数が大きいほど取り逃しが増え警戒心の強いシカを生み出すことが懸念された。時間経過にともなう目撃頭数の変化は見られなかったが, 捕獲頭数は減少しており, 時間経過にともなう捕獲効率の低下が示唆された。有害鳥獣捕獲における収支額は一人あたり全体の平均で673円/時間であった。捕獲効率や収支状況は構成した班によって異なっていた。以上の結果から, 詳細なデータを元に捕獲の効果とコストを検証しながら最適な個体数調整の方法を模索していくことが重要であると考えられた。We evaluated the efficiency and cost of nuisance deer (Cervus nippon yesoensis) population control by shooting conducted in Ashoro Research Forest of Kyushu University. We also analyzed the relationships between the catch efficiency and the trend of the deer population size. 282 person (742 person-hours) were taken in the period of the population control. We found 1,711 deer on 420 opportunities for sighting of deer. In most cases, only one deer was captured per one sighting. The larger number of deer in a group sighted, the larger number of deer would be missed. It is concerned about increase in the vigilance of deer. The number of sighted deer per one opportunity did not change with time after the control started, while the efficiency of catch decreased. The balance payment of the population control was 673 yen/hour on average. The efficiency and cost differed with hunting group. The results of our study confirmed that it is important to explore the adequate method of the population control with evaluation of the efficiency and cost

Dynamics of Sasa borealis (Hack.) Makino et Shibata community induced by the grazing of sika deer (Cervus nippon) : The change from 2003 to 2014 in Shiiba Research Forest, Kyushu University

九州山地中央部に位置する九州大学宮崎演習林(2, 915ha)において, 2003年と2014年にスズタケの健全度調査を行い, ニホンジカによる摂食がスズタケの分布に及ぼす影響を評価した。2003年では三方岳団地(2, 282ha), 萱原山団地(146ha)の大部分でスズダケが消失していたが, 津野岳団地(487ha)ではほとんどの林地でスズタケが生育していた。2014年には三方岳団地および萱原山団地において前回の調査時に消失していたスズタケが回復した場所はなかった。一方、津野岳団地においてはスズタケの衰退が進行し, 大部分でスズタケが消失していた。津野岳団地で実施したスポットライトセンサスの結果, 近年の同団地におけるニホンジカ個体数に急激な増加が見られており, そのことが津野岳団地での急激なスズタケの衰退に繋がったと考えられた。また, スズタケが残存する場所の地形的特徴や林分の特徴などを検討した結果, 標高が低く, 施業が近年実施された場所でスズタケが残る傾向にあった。The distribution patterns of Sasa borealis (Hack.) Makino et Shibata in the Shiiba Research Forest, Kyushu University (2,915ha) were compared between 2003 and 2014, to evaluate the effects of sika deer (Cervus nippon) on the forest floor vegetation. In 2003, S. borealis was not observed in most of Sampo-dake area (2,282 ha) and Kayahara-yama area (146 ha), while it was observed in most of Tsuno-dake area (487 ha). In 2014, S. borealis was declined in most of Tsuno-dake area. We recently obseved a rapid increase in sika deer density in the Tsuno-dake area on spotlight census. There was no area in which S. borealis recovered. S. borealis tended to remain in low elevation and in the area where silvicultural manipulation had been conducted during the period between the surveys