Quantitative Assessment of the Benefits of Trade Facilitation

Trade transaction costs (TTCs) related to border procedures vary depending on the efficiency and integrity of interacting businesses and administrations, the characteristics or kind of goods, and the size and type of businesses. Total costs may be seen as being composed of directly incurred costs, such as expenses relating to supplying information and documents to the related authority, and indirectly incurred costs, such as those arising from procedural delays. Empirical studies suggest that directly and indirectly incurred TTCs each amount to 1-15 per cent of traded goods’ value. Moreover, empirical evidence suggests that TTCs for agro-food products are higher than those for manufactured goods, as agro-food shipments are subject to special border procedures, such as sanitary and phyto-sanitary controls. Also, small and medium-sized enterprises face cost-disadvantages. In light of this diversity in TTCs, the potential for the realisation of benefits from trade facilitation varies across countries, sectors, and types of traders. In cases where best practices are already applied, further efficiency gains will be difficult to achieve. But if border clearance costs are substantially above those encountered under best practices, room for improvement through suitable measures of trade facilitation will tend to exist. The model-based analysis of the economic impacts of trade facilitation carried out in this study differs from earlier research by taking several salient features of import and export procedures into account. In particular, the differing characteristics of direct and indirect TTCs are represented, and country-specific differences in trade facilitation potential are reflected according to empirical information on border waiting times and survey-based evidence on the quality of border processes. In addition, the higher TTCs for agro-food products and small and medium-sized enterprises are incorporated into the analysis. The analysis does not evaluate the economic and trade impact of specific trade facilitation measures or instruments, such as those that might result from a possible future WTO agreement on trade facilitation. Instead, the aim of the assessment is to better represent empirical characteristics of the border process in model-based analysis and to identify those features that crucially affect the results and that, therefore, deserve to be further explored in future analysis. Several scenarios of hypothetical, multilateral trade facilitation efforts are evaluated, focusing on the comparison of scenarios rather than the overall welfare gains that might result from trade facilitation.Trade facilitation, customs procedures, documentary requirements, waiting times, CGE modelling

In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer. However, in other types of cancer including malignant brain tumors, LAT1 is not always highly expressed. To expand the possibility of BNCT for these cases, we previously developed poly-arginine peptide (polyR)-conjugated mercaptoundecahydrododecaborate (BSH). PolyR confers the cell membrane permeability and tumor selectivity of BSH. However, the molecular determinants for the properties are not fully understood. In this present study, we have identified the cluster of differentiation 44 (CD44) protein and translational machinery proteins as a major cell surface target and intracellular targets of BSH-polyR, respectively. CD44, also known as a stem cell-associated maker in various types of cancer, is required for the cellular uptake of polyR-conjugated molecules. We showed that BSH-polyR was predominantly delivered to a CD44(High) cell population of cancer cells. Once delivered, BSH-polyR interacted with the translational machinery components, including the initiation factors, termination factors, and poly(A)-biding protein (PABP). As a proof of principle, we performed BSH-polyR-based BNCT against glioma stem-like cells and revealed that BSH-polyR successfully induced BNCT-dependent cell death specifically in CD44(High) cells. Bioinformatics analysis indicated that BSH-polyR would be suitable for certain types of malignant tumors. Our results shed light on the biochemical properties of BSH-polyR, which may further contribute to the therapeutic optimization of BSH-BNCT in the future

Radiographic comparison between male and female patients with lumbar spondylolysis

We studied the lumbar spines of 117 adults (39 women and 78 men) with spondylolysis unrelated to low back pain using multidetector computed tomography (CT). Of the 117 subjects with spondylolysis, including five with multiple-level spondylolysis, there were 124 vertebrae with spondylolysis. In adult lumbar spines with unilateral spondylolysis, there was no significant difference between the incidence of spondylolisthesis in female and male subjects. However, in those with bilateral spondylolysis, there was a significantly higher incidence of spondylolisthesis in female subjects (90.9%) than in males (66.2%). Furthermore, females with bilateral spondylolysis had significant more slippage than males. Lumbar index and lumbar lordosis were not significantly different between male and female subjects, and did not significantly correlate with slippage. In conclusion, to treat acute spondylolysis in adolescents, it is important to obtain bony union at least unilaterally, especially in female subjects, to prevent further slippage

Relation between abnormal synergy and gait in patients after stroke

[Background]The abnormal synergy seen in patients after stroke is considered to limit the ability of these patients. However, in the lower extremity, antigravity torque generation rather than precise movement is needed for functions such as sit-to-stand movement and gait. Therefore, the ability to generate torque may be important either as a primary movement or as an abnormal synergy. We attempted to quantify the torque generation in the lower limb, selectively and as an abnormal synergy, and its relation with gait. [Methods]Selectively generated plantar flexion torque in the ankle and plantar flexion torque secondarily generated accompanying maximal hip extension (i.e., torque generated with abnormal synergy) were measured in subjects after stroke and control subjects. In subjects after stroke, secondary torque generation while controlling hip extension torque as 25%, 50%, and 75% of the maximal hip extension was also measured. The relation of torque generation with the gait speed and timed-up-and go test (TUG) was also analyzed. [Results]In subjects after stroke, there was no difference between the amount of plantar flexion torque generated secondarily and the selectively generated torque, whereas the selective torque was significantly greater in control subjects. Pearson product?moment correlation coefficient analysis revealed that TUG speed is related to secondarily generated torque accompanying maximal hip extension but not with selectively generated torque. [Conclusion] Secondarily generated torque was found to be a factor that affects TUG speed, and the ability to generate torque even through abnormal synergy may help for gait ability in subjects after stroke

Ixazomib が奏効している心アミロイドーシス合併多発性骨髄腫

　Ixazomib は，経口のプロテアソーム阻害薬であり，特に非注射薬の組み合わせが選択される多発性骨髄腫患者の再発難治例にとって有用な治療薬である．今回，我々はIxazomib が奏効している心アミロイドーシス合併多発性骨髄腫を経験したため報告する．症例は50歳代女性で，20XX 年10月心不全精査のため当院循環器内科入院となり，精査にて洞不全症候群（type3），心アミロイドーシスと診断された．洞不全症候群（type3）に対して心臓ペースメーカー移植術が施行され，血液検査にてM 蛋白を認めたため当科紹介となった．骨髄検査では形質細胞の増加を認め，AL アミロイドーシス（心臓，消化管）合併多発性骨髄腫（IgG‐λ with BJP）と診断した．20XX 年12月から治療を開始．VRD 療法を１コース施行中に，ペースメーカー波形ではない不整脈が多発し，うっ血性心不全の併発や，心源性脳梗塞による左完全片麻痺を発症した．VRD 療法は継続困難と判断し，elotuzumab 併用RD 療法に変更し治療を施行した．２コースでPD となったため，脳梗塞の発症によるADL の低下があることから，施設入所をふまえて外来通院頻度が少ない治療法として，Ixazomib 併用RD 療法を選択し治療を開始した．治療効果および忍容性は良好で，M 蛋白の順調な低下を認め，心不全の増悪なく経過している．心アミロイドーシス合併多発性骨髄腫は，治療に伴い致死性不整脈や心不全を併発することが多い．プロテアソーム阻害剤であるbortezomib 投与にて，不整脈や心不全の併発症状が出現していたが，経口プロテアソーム阻害剤であるixazomib の投与では，不整脈や心不全を併発させることなく，治療が継続し得た．　Ixazomib is an oral proteasome inhibitor that is useful for the treatment of recurrent refractory cases, particularly when a non-injection combination drug therapy is chosen for the patient. Here, we report a case of cardiac amyloidosis treated with ixazomib in a patient with multiple myeloma. The patient was a 50-year-old woman hospitalized in the cardiovascular medicine department of our hospital in October 20XX for close examination of cardiac failure. On the basis of the test findings, sick sinus syndrome (type 3) and cardiac amyloidosis were diagnosed. A heart pacemaker transplantation was performed for the sick sinus syndrome (type 3), and additional tests indicated M-protein expression; thus, the patient was referred to our department. A bone marrow test revealed increased plasma cells, which led to the diagnosis of immunoglobulin light chain amyloidosis (heart and digestive tract) secondary to multiple myeloma (IgG‐λ with BJP). Treatment was initiated in December 20XX. During the first course of VRD treatment, multiple non-pacemaker waveform arrhythmias and congestive heart failure occurred. Left total hemiplegia due to cardioembolic stroke occurred. We judged it difficult to continue the VRD treatment, so we switched the treatment to concomitant elotuzumab and RD therapy. After 2 courses, the patient became PD. With a decrease in ADL due to the onset of cerebral infarction and considering the possible need for institutionalization, ixazomib combined with RD therapy was initiated as treatment to reduce the frequency of outpatient visits. The treatment efficacy and tolerance were good, the M-protein expression level decreased gradually. Her progress was uneventful with no worsening of cardiac failure. Cardiac amyloidosis secondary to multiple myeloma is commonly associated with treatment-related lifethreatening arrhythmias and cardiac failure. Treatment with the proteasome inhibitor bortezomib is associated with the onset of arrhythmias and cardiac failure. However, treatment with the oral proteasome inhibitor ixazomib can be continued without onset of arrhythmia and cardiac failure

Pneumonia Caused by Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza Virus: A Multicenter Comparative Study

Background: Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. Methods: A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. Results: Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. Conclusions: Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings

Red-cell aplasia due to persistent human parvovirus B19 infection three years after umbilical cord blood transplantation-a case study

　造血幹細胞移植後に生じる貧血は，骨髄の造血能低下やウイルス感染症等の様々な背景が原因となることがあり，診断が困難であることが多い．ヒトパルボウイルス B19（human parvovirus B19：PVB19）は伝染性紅斑の原因ウイルスであり，遺伝性球状赤血球症等の赤血球寿命が短縮している溶血性貧血患者では，急性赤芽球癆を呈することが知られている．PVB19は移植患者を含む免疫不全状態の患者で慢性貧血を引き起こすことがあり，腎移植患者などでの報告例は多く存在するが，臍帯血移植後における PVB19感染による後天性赤芽球癆の症例の報告はほとんどない．今回我々は，臍帯血移植が成功したのち３年を経て発症した PVB19が４か月以上持続感染している症例を経験したので報告する．　Onset of anemia after hematopoietic stem cell transplantation can be caused by various background factors such as reduced hematopoiesis of the bone marrow and viral infection. Therefore, diagnosis is often difficult. Human parvovirus B19 (PVB19) due to acquired pure red-cell aplasia is the causative virus of erythema infectiosum, and it is well known that patients with hemolytic anemia with a short erythrocyte life span such as in the case of hereditary spherocytosis present with acute red-cell aplasia. PVB19 can cause chronic anemia in immunocompromised patients, including transplantation patients, and while there are many reported cases in kidney transplant patients, etc., there are few reported cases of cord blood transplantation. Here, we report a case of onset of PVB19 that occurred three years after successful umbilical cord blood transplantation and caused persistent infection for over a period of four months

クリプトコッカス髄膜炎を発症したCD4リンパ球減少症の２例

　クリプトコッカス感染症はCryptococcus neoformans による真菌感染症であり，免疫不全患者に発症しやすい．今回，我々はCD4リンパ球減少を認め，クリプトコッカス髄膜炎を発症した２例を経験したので報告する．症例１は，40歳代男性で不明熱のため受診した．血液検査でリンパ球930/μL，髄膜刺激症状はなかったが，髄液検査にてクリプトコッカス菌体が検出され，血液培養からも検出された．CD4 72.5/μL と低値であり，HIV 抗体陽性であった．クリプトコッカス髄膜炎を発症したAIDS 患者と診断した．症例２は，20歳代女性で不明熱のため受診した．血液検査でリンパ球510/μL，髄膜刺激症状はなかったが，髄液検査にてクリプトコッカス菌体が検出され，血液培養からも検出された．CD4 19.4/μL と低値であったが，HIV 抗体陰性で原発性免疫不全症や他の免疫不全となる原因は認められなかった．Idiopathic CD4 lymphocytopenia（ICL）に発症したクリプトコッカス髄膜炎と診断した．AIDS とICL がそれぞれ原因となったクリプトコッカス髄膜炎であった．前者での本症併発は2.4 %，後者での併発は19.7 % と報告されている．HIV非感染のクリプトコッカス髄膜炎をみた際にはICL によるCD4リンパ球減少症を考える必要がある．死に至ることもまれではないクリプトコッカス髄膜炎であるが，治療が奏効し１年以上経過しているため報告する．　Cryptococcal infections are fungal infections caused by Cryptococcus neoformans. This infection develops more commonly in immunocompromised patients. We report two cases of cryptococcal meningitis that developed as a result of CD4 lymphocytopenia. Case 1 was a man in his 40s who presented with a fever of unknown origin. A blood test revealed a lymphocyte count of 930/μL, with no meningeal irritation; however, examination of his cerebrospinal fluid detected cryptococcal bodies, which was also confirmed by blood culture. In addition, the patient had a low CD4 count of 72.5/μL, and was HIV antibodypositive. We thus diagnosed him as an AIDS patient who developed cryptococcal meningitis. Case 2 was a woman in her 20s who also presented with a fever of unknown origin. A blood test revealed a lymphocyte count of 510/μL, with no meningeal irritation; however, examination of her cerebrospinal fluid detected cryptococcal bodies, which was confirmed by blood culture. Despite the patient having a low CD4 count of 19.4/μL, she was HIV antibody-negative, and there was no evidence of primary immunodeficiency or any other causes of immune deficiency. Accordingly, we diagnosed this patient as cryptococcal meningitis that developed as a result of idiopathic CD4 lymphocytopenia (ICL). In the above cases, cryptococcal meningitis developed as a result of AIDS and ICL, respectively. The incidence rates of this complication are reported as 2.4% for the former and 19.7% for the latter. When cryptococcal meningitis without HIV infection is observed, it is necessary to consider the possibility of CD4 lymphocytopenia due to ICL. Although cryptococcal meningitis can be fatal, treatment was successful in both cases, and more than one year has elapsed since their initial presentation