Limitation of Efficiency: Strategy-Proofness and Single-Peaked Preferences with Many Commodities

In this paper, we study a resource allocation problem of economies with many commodities and single-peaked preferences. It is known that the uniform rule is the unique allocation mechanism satisfying strategy-proofness, Pareto efficiency and anonymity, if the number of good is only one and preferences are single peaked. (Sprumont [7].) However, if the number of goods is greater than one, the situation drastically changes and a tradeoff between efficiency and strategy-proofness arises. The generalized uniform rule in multiple-commodity settings is still strategy-proof, but not Pareto efficient in general. In this paper, we show that in a class of all strategy-proof mechanisms the generalized uniform rule is a "second best" strategy-proof mechanism in that there is no other strategy-proof mechanism which gives a "better" outcome than the generalized uniform rule in terms of Pareto domination.

官製青年団における体育・スポーツの展開とその特質 : 大正・昭和戦前期石川県の事例から

取得学位:博士（学術）,授与番号:博士甲第43号,授与年月日:2002年3月225日,授与大学:金沢大学,論文審査委員長:大久保, 英哲, 論文審査委員:　江森, 一郎 / 橋本, 哲

High Human T Cell Leukemia Virus Type-1(HTLV-1) Provirus Load in Patients with HTLV-1 Carriers Complicated with HTLV-1-unrelated disorders

<p>Abstract</p> <p>Background</p> <p>To address the clinical and virological significance of a high HTLV-1 proviral load (VL) in practical blood samples from asymptomatic and symptomatic carriers, we simultaneously examined VL and clonal expansion status using polymerase chain reaction (PCR) quantification (infected cell % of peripheral mononuclear cells) and Southern blotting hybridization (SBH) methods.</p> <p>Results</p> <p>The present study disclosed extremely high VL with highly dense smears with or without oligoclonal bands in SBH. A high VL of 10% or more was observed in 16 (43.2%) of a total of 33 samples (one of 13 asymptomatic carriers, 8 of 12 symptomatic carriers, and 7 of 8 patients with lymphoma-type ATL without circulating ATL cells). In particular, an extremely high VL of 50% or more was limited to symptomatic carriers whose band findings always contained at least dense smears derived from polyclonally expanded cells infected with HTLV-1. Sequential samples revealed that the VL value was synchronized with the presence or absence of dense smears, and declined at the same time as disappearing dense smears. Dense smears transiently emerged at the active stage of the underlying disease. After disappearance of the smears, several clonal bands became visible and were persistently retained, explaining the process by which the clonality of HTLV-1-infected cells is established. The cases with only oligoclonal bands tended to maintain a stable VL of around 20% for a long time. Two of such cases developed ATL 4 and 3.5 years later, suggesting that a high VL with oligoclonal bands may be a predisposing risk to ATL.</p> <p>Conclusion</p> <p>The main contributor to extremely high VL seems to be transient emergence of dense smears detected by the sensitivity level of SBH, corresponding to polyclonal expansion of HTLV-1-infected cells including abundant small clones. Major clones retained after disappearance of dense smears stably persist and acquire various malignant characteristics step by step.</p

Anionic Complex with Efficient Expression and Good Safety Profile for mRNA Delivery

We previously found that a complex comprising plasmid DNA (pDNA), polyethylenimine (PEI), and γ-polyglutamic acid (γ-PGA) had high transgene efficiency without cytotoxicity in vitro and in vivo. However, messenger RNA (mRNA) remains an attractive alternative to pDNA. In this study, we developed a safe and effective delivery system for mRNA to prevent its degradation and efficiently deliver it into target cells. Various cationic and anionic complexes were produced containing PEI, γ-PGA, and an mRNA encoding firefly luciferase. Their physicochemical properties and cytotoxicities were analyzed and the in vitro and in vivo protein expression were determined. The cationic mRNA/PEI complex showed high in vitro protein expression with strong cytotoxicity. The anionic complex was constructed as mRNA/PEI8/γ-PGA12 complex with a theoretical charge ratio of 1:8:12 based on the phosphate groups of the mRNA, nitrogen groups of PEI, and carboxylate groups of γ-PGA. It was stable and showed high in vitro protein expression without cytotoxicity. After intravenous administration of mRNA/PEI8/γ-PGA12 complex to mice, high protein expression was observed in the spleen and liver and slight expression was observed in the lung over 24 h. Thus, the newly constructed mRNA/PEI8/γ-PGA12 complex provides a safe and effective strategy for the delivery of mRNA

Post-operative infection of endoscopic submucosal dissection of early colorectal neoplasms: a case?controlled study using a Japanese database

What is known and objective Endoscopic submucosal dissection of early colorectal neoplasms (ESD-ECN) is known to be an operation with risk of contamination, possibly requiring pre-operative antimicrobial prophylaxis for the prevention of post-operative infection. However, an evaluation of the need for pre-operative antimicrobial prophylaxis for ESD-ECN has yet to be reported. The objective of this study was to determine whether pre-operative antimicrobial prophylaxis is associated with a reduced incidence of post-operative infection following ESD-ECN. Methods The present retrospective case-controlled study utilized a database built from the medical records of 14 university hospitals throughout Japan. Patients who were admitted and discharged from the hospital from April 2012 to October 2013 and who had undergone ESD-ECN were included in the study. Patients who had been undergone any other operation during their course of hospitalization, and patients who were prescribed antimicrobial agents for reasons other than post-operative infection or for prophylaxis were excluded. Characteristics of the study population, pre-operative antimicrobial prophylaxis and antimicrobial therapy for post-operative infection were investigated. In addition, we compared the characteristics of patients with post-operative infection (PI) and those with no post-operative infection (NPI). Univariate analyses were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). Results and discussion We obtained the records of 522 patients who had undergone ESD-ECN from the database. After application of exclusion criteria, 421 patients were enrolled. The post-operative infection rate was 1・2%. Peritonitis was found most to be the most common post-operative infection (44%). Pre-operative antimicrobial prophylaxis was used for 314 patients (75%), with a median duration of 3・0 (range 1-11) days. Cefotiam was most frequently prescribed for pre-operative antimicrobial prophylaxis (56%). Antimicrobial therapies were started 1-10 days after ESD-ECN for a duration of 1-14 days. Pre-operative antimicrobial prophylaxis was not associated with post-operative infection rate, with an OR (95% CI) of 0・73 (0・08-6・61). However, digestive tract perforation was shown to be associated with post-operative infection and had an OR (95% CI) of 17・1 (1・66-176・45). What is new and conclusion Post-operative infection is an exceedingly rare event following ESD-ECN. Pre-operative antimicrobial prophylaxis had no significant effect on post-operative infection following ESD-ECN and thus may be unnecessary. Instead, prevention of digestive tract perforation may be more critical for the decrease in post-operative infections. Univariate analyses of PI vs. NPI

成人T細胞白血病/リンパ腫のクローン構成を評価する新規方法の開発

長崎大学学位論文 [学位記番号]博（医歯薬）甲第1308号 [学位授与年月日]令和3年3月3

Induction of mucosal immunity by pulmonary administration of a cell-targeting nanoparticle

We previously found that a nanoparticle constructed with an antigen, benzalkonium chloride (BK) and γ-polyglutamic acid (γ-PGA) showed high Th1 and Th2-type immune induction after subcutaneous administration. For prophylaxis of respiratory infections, however, mucosal immunity should be induced. In this study, we investigated the effect of pulmonary administration of a nanoparticle comprising ovalbumin (OVA) as a model antigen, BK, and γ-PGA on induction of mucosal immunity in the lungs and serum. The complex was strongly taken up by RAW264.7 and DC2.4cells. After pulmonary administration, lung retention was longer for the OVA/BK/γ-PGA complex than for OVA alone. OVA-specific serum immunoglobulin (Ig)G was highly induced by the complex. High IgG and IgA levels were also induced in the bronchoalveolar lavage fluid, and in vivo toxicities were not observed. In conclusion, we effectively and safely induced mucosal immunity by pulmonary administration of an OVA/BK/γ-PGA complex

Gamma-polyglutamic acid-coated vectors for effective and safe gene therapy.

In the present study, we developed some novel gene delivery vectors, coated cationic complexes with gamma-polyglutamic acid (gamma-PGA) for effective and safe gene therapy. Cationic complexes were constructed with pDNA and cationic vectors, such as poly-L-arginine hydrochloride (PLA), poly-L-lysine hydrobromide (PLL), N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA)-cholesterol (Chol) liposomes, and DOTMA-dioleylphosphatidylethanolamine (DOPE) liposomes. The cationic complexes showed high gene expression with strong cytotoxicity in melanoma B16-F10 cells. The cationic complexes were also strongly toxic to erythrocytes. On the other hand, the gamma-PGA was able to coat all cationic complexes and form stable nano-sized particles with negative charges. These gamma-PGA-coated complexes had high gene expression without cytotoxicity and toxicities to the erythrocytes. In in vivo transfection experiments, polyplexes showed high transfection efficiency over 10(5) RLU/g in the lung tissue after intravenous injection, although gamma-PGA-coated polyplexes showed a high value in the spleen. High transfection efficiency in lipoplexes and gamma-PGA-coated lipoplexes was observed in the spleen and lung. Thus, gamma-PGA-coated vectors are useful for clinical gene therapy

Predicting the outcome of chronic kidney disease by the estimated nephron number: The rationale and design of PRONEP, a prospective, multicenter, observational cohort study

<p>Abstract</p> <p>Background</p> <p>The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number.</p> <p>Methods/Design</p> <p>The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice.</p> <p>Discussion</p> <p>This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice.</p> <p>Trial registration</p> <p>UMIN-Clinical Trial Registration, UMIN000004784.</p

Depth of response may predict clinical outcome in patients with recurrent/metastatic head and neck cancer treated with pembrolizumab-containing regimens

BackgroundPembrolizumab-containing regimens are standards of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). The depth of response (DpR) predicts the survival of patients with several types of solid cancers; however, its association with the survival outcomes of patients with R/M HNSCC treated with pembrolizumab-containing regimens remains unclear.MethodsThis study included 66 patients with R/M HNSCC who received a pemblolizumab-containing regimen as a first-line therapy at Tohoku University Hospital, Sendai, Japan. The patients’ characteristics, combined positive score, baseline tumor size, tumor response, DpR, overall survival (OS), progression-free survival (PFS), PFS2, and adverse events were reviewed. The associations between DpR and survival outcomes were analyzed.ResultsThe 1 year-OS and 1 year-PFS rates of pembrolizumab-containing regimens were 69.4% and 24.4%, respectively. The response rate was 28.8%. The mean and median values of tumor change from baseline were 5.1% and −9.0%. In the correlation analysis, a significant negative correlation was observed between tumor change rate from baseline and survival outcomes (OS: r= −0.41, p=0.0017; PFS: r=−0.49, p&lt;0.001). In the multivariate analysis, DpR with tumor change of ≤−45 was associated with better OS and PFS.ConclusionDpR induced by pembrolizumab-containing regimens may be a predictive factor for OS and PFS in patients with R/M HNSCC