Foreign and Domestic R&D Investment

A considerable share of R&D investment is due to multinational firms that simultaneously operate R&D bases at home and abroad. The existing empirical literature on R&D investment has however ignored the possibility that domestic and foreign R&D investments are simultaneously decided. In this paper, we draw on the technological opportunity, appropriability, and demand framework suggested by Cohen and Klepper (1996) to develop a simple model of foreign and domestic R&D investment. We test the model's predictions concerning the ratio of foreign to domestic R&D investment on a sample of 146 Japanese multinational firms' R&D investments in Japan and the United States in 1996. The empirical results confirm that the foreign R&D ratio depends on relative technological opportunities, relative demand conditions, and a proxy for firm-level R&D productivity. When differentiating between research and development activities, foreign research is driven by technological opportunity and foreign development by the demand factor, as expected.R&D, multinational firms, Foreign Direct Investment

Effects of Combined Low Glutathione with Mild Oxidative and Low Phosphorus Stress on the Metabolism of Arabidopsis thaliana

Plants possess highly sensitive mechanisms that monitor environmental stress levels for a dose-dependent fine-tuning of their growth and development. Differences in plant responses to severe and mild abiotic stresses have been recognized. Although many studies have revealed that glutathione can contribute to plant tolerance to various environmental stresses, little is known about the relationship between glutathione and mild abiotic stress, especially the effect of stress-induced altered glutathione levels on the metabolism. Here, we applied a systems biology approach to identify key pathways involved in the gene-to-metabolite networks perturbed by low glutathione content under mild abiotic stress in Arabidopsis thaliana. We used glutathione synthesis mutants (cad2-1 and pad2-1) and plants overexpressing the gene encoding γ-glutamylcysteine synthetase, the first enzyme of the glutathione biosynthetic pathway. The plants were exposed to two mild stress conditions—oxidative stress elicited by methyl viologen and stress induced by the limited availability of phosphate. We observed that the mutants and transgenic plants showed similar shoot growth as that of the wild-type plants under mild abiotic stress. We then selected the synthesis mutants and performed multi-platform metabolomics and microarray experiments to evaluate the possible effects on the overall metabolome and the transcriptome. As a common oxidative stress response, several flavonoids that we assessed showed overaccumulation, whereas the mild phosphate stress resulted in increased levels of specific kaempferol- and quercetin-glycosides. Remarkably, in addition to a significant increased level of sugar, osmolytes, and lipids as mild oxidative stress-responsive metabolites, short-chain aliphatic glucosinolates over-accumulated in the mutants, whereas the level of long-chain aliphatic glucosinolates and specific lipids decreased. Coordinated gene expressions related to glucosinolate and flavonoid biosynthesis also supported the metabolite responses in the pad2-1 mutant. Our results suggest that glutathione synthesis mutants accelerate transcriptional regulatory networks to control the biosynthetic pathways involved in glutathione-independent scavenging metabolites, and that they might reconfigure the metabolic networks in primary and secondary metabolism, including lipids, glucosinolates, and flavonoids. This work provides a basis for the elucidation of the molecular mechanisms involved in the metabolic and transcriptional regulatory networks in response to combined low glutathione content with mild oxidative and nutrient stress in A. thaliana

Cryptosporidiosis in a transplant recipient with severe intractable diarrhea : Detection of Cryptosporidium oocysts by intestinal biopsies

Disseminated Cryptosporidium infection results in manifestations similar to those of graft‐versus‐host disease (GVHD), which hampers the detection of Cryptosporidium infection after allogeneic hematopoietic stem cell transplantation. Surveillance of oocysts on the surface of intestinal epithelial cells is needed for early and appropriate detection of Cryptosporidium infection in transplant recipients on immunosuppressants with severe intractable diarrhea. We present the first case of Cryptosporidium meleagridis infection in Japan after allogeneic cord blood transplantation

Multiple myeloma with high adenosine deaminase expression

A 50-year-old man with immunoglobulin A type multiple myeloma (MM) was referred to our hospital after bortezomib therapy. He had high alkaline phosphatase and lactate dehydrogenase levels. Computed tomography showed osteolytic and osteoblastic bone lesions. Response to salvage chemotherapy was temporary, and he developed a right pleural effusion with high adenosine deaminase (ADA) levels. He died from bleeding associated with a pelvic bone fracture 9 months later. ADA mRNA expression and ADA secretion of the MM cells from the patient were higher than those from myeloma cell lines tested. Clinical relevance of high ADA expression in MM cells is warranted

急性期医療を受ける患者の願い

目的：患者の地域での暮らしの希望と療養上の目標を中心に構造化した看護のプロセス”Nursing Care for Patient Goals”（NCPG）に患者の視点から示唆を得るため急性期医療を受ける患者が看護師に知ってほしい情報と療養の目標に対して求める看護を明らかにした． 方法：１特定機能病院において入院中または入院予定の20歳以上の患者を対象として質問紙調査を２回（2017年，2018年）に実施した．調査内容は基本属性，調査Ⅰ（2017年）は先行研究を基に抽出した患者情報23項目について看護師に知って欲しいと思う程度，最も大事と思う項目とその選択理由，調査Ⅱ（2018年）は自分の療養の目標について求める看護であった．統計分析は記述統計，因子分析，t 検定を用いた．自由記述によるデータは質的記述的分析を行った． 結果：調査Ⅰの有効回答数は448名で，看護師に知ってほしい自分の情報として【第１因子：社会的役割と環境】【第２因子：病気の理解・受け入れと心理】【第３因子：身体的状態と生活の仕方】【第４因子：暮らしの希望と自己決定】が抽出された．65歳未満と比較して65歳以上の対象者は第１因子が高い傾向にあった．また第４因子を最も大事と思う項目の選択理由について， “希望・目標がなきゃ生きていけない” という表現が特徴として出された．調査Ⅱの有効回答数は416名で，多数の対象者が自分の目標を医療者と共有することが重要だと感じており，受けたい看護として，傍にいて寄り添う看護，治療・症状への専門的な看護，地域での暮らしの自立への看護が抽出された． 結論：患者の視点から看護師に知ってほしい情報として４つの因子と自分の目標を分ってほしいとする対象者の願いは，希望と目標を基盤としたNCPG の考え方と一致しており，目標達成のために受けたい看護の３つの視点が示唆された．Objective : This study aimed to identify information on care of patients receiving acute care for life in community from the patientsʼ perspective and to obtain suggestions for “Nursing Care for Patient Goals”（NCPG）. Method : The subjects were patients receiving acute care and aged 20 years and above. They were given self-administered questionnaires. Survey Ⅰ（2017）consisted of a questionnaire that was based on previously collected qualitative data and comprised 23 Likert-scale questions and free descriptive questions on the reasons for selecting the most important item. Survey Ⅱ（2018）consisted of questionnaire that was comprised of three Likert-scale questions on goals and a free descriptive question on care for the achievement of goals. Statistical analysis included descriptive statistics, factor analysis, and t-test. Data from free-text descriptions were analyzed using qualitative descriptive analysis. Results : Survey Ⅰ : data from 448 valid responses were subjected to factor analysis to determine the factor structure. The following factors were identified from the patientsʼ perspectives: 1） social role and environment, 2） understanding/acceptance and psychological state, 3） physical condition and life, and 4） hope and decision-making for life. In addition, a qualitative and inductive approach was employed to analyze participantsʼ descriptive responses about the reason for selecting the most important item. The characteristic description of why participants selected “hope and decision-making of life” was “I cannot live without hope.” Survey Ⅱ : data from 416 valid responses were analyzed. The majority of participants felt it was important to share their goals with their healthcare professionals. A qualitative and inductive approach was employed to analyze the participantsʼ descriptive responses to care for goals achievement. The care desired by participants was categorized as “being with”, “professional care”, and “self-care support”. Conclusion : The factors that patients wanted nurses to know were consistent with the components of “NCPG.” The care that patients desire to achieve their goals was clarified

患者の希望を地域につなぐための患者状態とニーズ

目的：急性期医療を受ける患者の地域での生活を視野に入れた看護を展開するために患者の情報と看護の視点について明らかにすることを目的とした． 方法：特定機能病院に勤務する中堅以上の看護師３３名を対象に，地域での生活を視野に入れた患者の情報と看護の視点についてフォーカス・グループ・インタビューを行い分析した． 結果及び考察：急性期医療を受ける患者の地域での生活に必要な情報と看護の視点として，コアカテゴリー《地域での生活を可能にするニーズ》が抽出された．さらに地域での生活を可能にするための状態とニーズとして【身体・生理的な状態とニーズ】，【生活の自立と安全の状態とニーズ】，【病気の受け入れと心理的反応の状態とニーズ】，【社会的環境の状態とニーズ】，【医療・療養への自己決定の状態とニーズ】の５つのカテゴリーに分類された．これらより，患者の暮らしの希望，療養の目標，５つの視点の状態からニーズを導き看護を展開する看護の過程として，“Nursing Care for Patient Goals（” NCPG）を構造化した． 結論：地域包括ケアシステムの中において急性期医療を受ける患者の情報と看護の視点として地域での生活を可能にするための５つの状態とそのニーズが重視されていた．Objective : The aim of this study was to identify information and care perspectives of nurses for patients leaving an acute care hospital for life in the community, and to consider appropriate nursing care in the community-based integrated care system. Method : Focus group interviews were conducted with 33 nurses working in an acute care hospital. The data were analyzed using qualitative inductive analysis. Results & Discussion : The core category “Needs to enable patients to live in the community” was extracted as the information and care perspective necessary for patients receiving acute care to leave hospital for life in the community. The information and care perspectives were classified into five conditions : physical/physiological condition and needs, life independence and safety status and needs, acceptance of/emotions about illness and needs, social environment and needs, and decision-making and needs. “Nursing Care for Patient Goals” was structured as a nursing process. Conclusion : We identified five conditions and their needs that would enable patients receiving acute care to leave hospital for life in the community

Safety, tolerability, pharmacokinetics, and pharmacodynamics of the afucosylated, humanized anti-EPHA2 antibody DS-8895a: a first-in-human phase I dose escalation and dose expansion study in patients with advanced solid tumors

BACKGROUND:Erythropoietin-producing hepatocellular receptor A2 (EPHA2) is overexpressed on the cell surface in many cancers and predicts poor prognosis. DS-8895a is a humanized anti-EPHA2 IgG1 monoclonal antibody afucosylated to enhance antibody-dependent cellular cytotoxicity activity. We conducted a two-step, phase I, multicenter, open-label study to determine the safety, tolerability, and pharmacokinetics of DS-8895a in patients with advanced solid tumors.METHODS:Step 1 was a dose escalation cohort in advanced solid tumor patients (six dose levels, 0.1-20 mg/kg) to determine Step 2 dosing. Step 2 was a dose expansion cohort in EPHA2-positive esophageal and gastric cancer patients. DS-8895a was intravenously administered every 2 weeks for the duration of the study, with a 28-day period to assess dose-limiting toxicity (DLT). Safety, pharmacokinetics, tumor response, and potential biomarkers were evaluated.RESULTS:Thirty-seven patients (Step 1: 22, Step 2: 15 [9: gastric cancer, 6: esophageal cancer]) were enrolled. Although one DLT (Grade 4 platelet count decreased) was observed in Step 1 (dose level 6, 20 mg/kg), the maximum tolerated dose was not reached; the highest dose (20 mg/kg) was used in Step 2. Of the 37 patients, 24 (64.9%) experienced drug-related adverse events (AEs) including three (8.1%) with Grade ≥ 3 AEs. Infusion-related reactions occurred in 19 patients (51.4%) but were manageable. All patients discontinued the study (evident disease progression, 33; AEs, 4). Maximum and trough serum DS-8895a concentrations increased dose-dependently. One gastric cancer patient achieved partial response and 13 patients achieved stable disease. Serum inflammatory cytokines transiently increased at completion of and 4 h after the start of DS-8895a administration. The proportion of CD16-positive natural killer (NK) cells (CD3-CD56+CD16+) decreased 4 h after the start of DS-8895a administration, and the ratio of CD3-CD56+CD137+ to CD3-CD56+CD16+ cells increased on day 3.CONCLUSIONS:Twenty mg/kg DS-8895a infused intravenously every 2 weeks was generally safe and well tolerated in patients (n = 21) with advanced solid tumors. The exposure of DS-8895a seemed to increase dose-dependently and induce activated NK cells