Instrumental Variables Estimation and Weak-Identification-Robust Inference Based on a Conditional Quantile Restriction

Extending the L1-IV approach proposed by Sakata (1997, 2007), we develop a new method, named the $rho_{tau}$-IV estimation, to estimate structural equations based on the conditional quantile restriction imposed on the error terms. We study the asymptotic behavior of the proposed estimator and show how to make statistical inferences on the regression parameters. Given practical importance of weak identification, a highlight of the paper is a proposal of a test robust to the weak identification. The statistics used in our method can be viewed as a natural counterpart of the Anderson and Rubin's (1949) statistic in the $rho_{tau}$-IV estimation.quantile regression; instrumental variables; weak identification

Histological Analysis of Failed Cartilage Repair after Marrow Stimulation for the Treatment of Large Cartilage Defect in Medial Compartmental Osteoarthritis of the Knee

Bone marrow-stimulating techniques such as microfracture and subchondral drilling are valuable treatments for full-thickness cartilage defects. However, marrow stimulation-derived reparative tissues are not histologically well-documented in human osteoarthritis. We retrospectively investigated cartilage repairs after marrow stimulation for the treatment of large cartilage defects in osteoarthritic knees. Tissues were obtained from patients who underwent total knee arthroplasty (TKA) after arthroscopic marrow stimulation in medial compartmental osteoarthritis. Clinical findings and cartilage repair were assessed. Sections of medial femoral condyles were histologically investigated by safranin O staining and anti-type II collagen antibody. Marrow stimulation decreased the knee pain in the short term. However, varus leg alignment gradually progressed, and TKA conversions were required. The grade of cartilage repair was not improved. Marrow stimulations resulted in insufficient cartilage regeneration on medial femoral condyles. Safranin O-stained proteoglycans and type II collagen were observed in the deep zone of marrow-stimulated holes. This study demonstrated that marrow stimulation resulted in failed cartilage repair for the treatment of large cartilage defects in osteoarthritic knees. Our results suggest that arthroscopic marrow stimulation might not improve clinical symptoms for the long term in patients suffering large osteoarthritic cartilage defects

Comparison between normal and loose fragment chondrocytes in proliferation and redifferentiation potential

Loose fragments in osteochondritis dissecans (OCD) of the knee require internal fixation. On the other hand, loose fragments derived from spontaneous osteonecrosis of the knee (SONK) are usually removed. However, the difference in healing potential between OCD- and SONK-related loose fragments has not been elucidated. In this study, we investigated proliferative activity and redifferentiation potential of normal cartilage-derived and loose fragment-derived chondrocytes. Cells were prepared from normal articular cartilages and loose fragment cartilages derived from knee OCD and SONK. Cellular proliferation was compared. Redifferentiation ability of pellet-cultured chondrocytes was assessed by real-time PCR analyses. Mesenchymal differentiation potential was investigated by histological analyses. Positive ratio of a stem cell marker CD166 was evaluated in each cartilaginous tissue. Normal and OCD chondrocytes showed a higher proliferative activity than SONK chondrocytes. Chondrogenic pellets derived from normal and OCD chondrocytes produced a larger amount of safranin O-stained proteoglycans compared with SONK-derived pellets. Expression of chondrogenic marker genes was inferior in SONK pellets. The CD166-positive ratio was higher in normal cartilages and OCD loose fragments than in SONK loose fragments. The OCD chondrocytes maintained higher proliferative activity and redifferentiation potential compared with SONK chondrocytes. Our results suggest that chondrogenic properties of loose fragment-derived cells and the amount of CD166-positive cells may affect the repair process of osteochondral defects

Study of Training Programs Designed for Teachers Providing Education in a Globalizing Society : The Development and Delivery of Lessons Based on Principles of Inclusive Teaching of Special Support Class Teachers and Normal Curriculum Teachers

本研究では，教育のグローバル化や共生社会の実現に向け，児童の個別教育ニーズに対応するための教員研修に着目し，教員間の共生関係や教師の力量形成につながる研修を実施した。研究の２年目にあたり，インクルーシブ教育研修を校内研修に位置づけ，その第１段階として異学級編成の集団における授業を実施した。その結果，特別支援学級と通常学級の教員の連携によって互いの専門性を生かし合いながら授業を行い，それぞれの児童実態の把握の仕方・捉え方の違いを検討すること，教科の指導については，学習したことを次の学習に生かしたり，生活に反映させたりするための視点について検討することを通して，成果と課題を得ることができた。This study investigated training programs designed to correspond to the demands of individual tutoring needs and the delivery of training programs. We aimed to enable teachers to develop stronger teaching skills as well as socializing ability with other teachers. In the second year, we set an inclusive educating training program as a staff training. At the first stage, teachers taught a class in a group of the different class organization. By teaching a class in which special support class teachers and normal curriculum teachers cooperated, emphasizing their ability and skills in their field, strong results and future tasks were clarified. The study examined how children are observed and recognized by each of the teaching parties, how children apply the method of learning obtained from one subject of study to another, and how children adapted the learned matter into real life situations

Review of global teacher lecture development training for the realization of symbiotic society: Taking into consideration the development of lessons in special support class and normal curriculum class can collaborate

本研究では，教育のグローバル化や共生社会の実現に向け，児童の個別教育ニーズに対応するための教員研修に着目し，教員間の共生関係や教師の力量形成につながる研修を実施した。研究の３年目にあたり，第２段階である複数学級編成の児童に対して，特別支援学級と通常学級の教員が協力して授業開発し，実践・協議を行った。その協議会では，授業における児童の学び合いやかかわりについての議論が中心となり，その代案ついても話し合いが行われた。また，授業者においても協議における多面的な見方・考え方から，新たな課題に気づくことができたことからも，研修の有効性を明らかにすることができた。今後の課題においては，児童の学び合いやかかわりについて，質を高めていく授業デザインを検討していく必要がある。This study focused on globalization and inclusive society by focusing on training programs designed to correspond towards demands of individual tutoring needs and conducting of training programs for teachers to develop stronger teaching skills as well as socializing ability between other teachers. In the third year of the research, special support classes and regular class faculty members cooperated with the second stage, multi-class organization children, to develop lessons, practice and consultation. Discussions on learning and engagement of students in classes focused mainly on discussions at the council, and discussions on alternatives were also held. In addition, it was possible for the lesson to clarify the effectiveness of the training also from being able to notice the new task from the multifaceted viewpoint and way of thinking in consultation. In the future tasks, we need to consider class design to improve the quality of learning and engagement of children

The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome

Objectives. This study aimed to determine the feasibility of cochlear implantation for sensorineural hearing loss in patients with Waardenburg syndrome. Method. A retrospective chart review was performed on patients who underwent cochlear implantation at the University of Tokyo Hospital. Clinical classification, genetic mutation, clinical course, preoperative hearing threshold, highresolution computed tomography of the temporal bone, and postoperative hearing outcome were assessed. Result. Five children with Waardenburg syndrome underwent cochlear implantation. The average age at implantation was 2 years 11 months (ranging from 1 year 9 months to 6 years 3 months). Four patients had congenital profound hearing loss and one patient had progressive hearing loss. Two patients had an inner ear malformation of cochlear incomplete partition type 2. No surgical complication or difficulty was seen in any patient. All patients showed good hearing outcome postoperatively. Conclusion. Cochlear implantation could be a good treatment option for Waardenburg syndrome

Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01)