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Abstract Background AP-7D is a newly developed preference-based measure (PBM) in East and Southeast Asia. However, no value set has been established yet. Comparison of the characteristics of value sets obtained by different methods is necessary to consider the most appropriate methodology for valuation survey of AP-7D. Method We surveyed the general population’s preference of AP-7D health states by four valuation methods (a) composite time trade-off (cTTO); (b) simple discrete choice experiment (DCE); (c) DCE with duration; and (d) ternary DCE. In Japan, we collected approximately 1,000 samples for cTTO tasks through a face-to-face survey and 2,500 samples for each of the three DCE tasks. Respondents were selected through quota sampling based on the sex and age. The cTTO data were analyzed using a linear mixed and tobit model; the DCE data were analyzed using a simple and panel conditional logit model. Where the results of the analysis showed inconsistencies, a constrained model was used. Results Since all the unconstrained models, except simple DCE, showed one or more inconsistencies, the constrained model was used for the analyses. The minimum values for the models were as follows: TTO model, -0.101; simple DCE model, -0.106; DCE with duration model, -0.706; ternary DCE model, -0.306. The score for the DCE with the duration model was much lower than that for the other models. Although the value sets for AP-7D differed among the four valuation methods, the ternary DCE model showed intermediate characteristics between those of the cTTO and DCE with duration models. As compared with to EQ-5D-5L, the distributions of all the scores on the Japanese AP-7D moved to the left. Although “Energy” was one of the domains with the least influence on the AP-7D score in all four models, “Burden to others” had the largest impact on the preferences. Conclusion We constructed four value sets using different TTO and DCE methods. Our findings are expected not only to contribute to the development of AP-7D, but also other preference-based measures.

IntroductionAlthough active vitamin D (VD) has been used both preoperatively and postoperatively to prevent hypocalcemia risk in patients undergoing total thyroidectomy, the role of 1,25-dihydroxyvitamin D (1,25(OH)2D) has not been examined. This study comprehensively investigated the effects of 1,25(OH)2D on calcium (Ca) concentrations after total thyroidectomy.MethodsSerum Ca, parathyroid hormone (PTH), and 1,25(OH)2D levels were measured in 82 patients with thyroid disease before and after surgery.ResultsSerum Ca, PTH, and 1,25(OH)2D levels decreased significantly on the morning of the first postoperative day. Notably, the decrease in 1,25(OH)2D concentration was significantly lower than that of PTH concentration (10.5 ± 33.4% vs. 52.1 ± 30.1%, p10 pg/mL group, the decrease in 1,25(OH)2D levels was significantly associated with postoperative hypocalcemia (p15 pg/mL group, a decrease in 1,25(OH)2D concentration was a significant factor, and the amount of PTH decrease was no longer significant.Conclusion1,25(OH)2D plays an important role in preventing sudden, severe hypocalcemia due to decreased PTH levels after total thyroidectomy, whereas high preoperative 1,25(OH)2D levels are a significant risk factor for postoperative hypocalcemia. Optimizing preoperative protocols to adjust Ca, PTH, and 1,25(OH)2D levels to improve the management of patients undergoing total thyroidectomy and to prevent extreme intraoperative PTH decreases may reduce the risk of hypocalcemia.

Abstract Background Little is known about predictive factors for survival outcomes of esophageal carcinoma (EC) patients who developed recurrence after undergoing multimodal therapies. We aimed to investigate long-term outcomes and identify prognostic factors in patients with relapsed EC, focusing especially on those with oligometastasis (OM). Methods EC patients who developed recurrence after curative treatments (radical esophagectomy or definitive chemoradiotherapy (dCRT)) between 2010 and 2017 were reviewed. Multivariate Cox hazards models were applied to determine independent predictors of poor post-recurrence survival (PRS). Results In total, 178 patients were included. The median PRS was 12.9 months. Of the 178 patients, 98 had OM and 80 non-OM (NOM) disease. The survival outcomes of patients with OM were significantly better than those of patients with NOM (P

Abstract Background Tumor-associated sarcoid reactions have been observed with various tumors; however, they have not been reported with uterine cancer. We present two cases of splenic sarcoid reactions that mimicked metastases a few years after uterine cancer surgery. Case presentation Case 1 involved a 67-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent open total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Three years after the initial surgery, computed tomography (CT) and positron emission tomography CT showed multiple splenic masses with increasing numbers and sizes. Splenic metastases were diagnosed, and laparoscopic splenectomy was performed. The histopathological analysis revealed sarcoid reactions in the spleen. Case 2 involved a 47-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Two years after the initial surgery, multiple splenic masses were observed. We performed laparoscopic splenectomy for the splenic metastases. Granuloma formations were identified in the splenic specimen and perisplenic lymph nodes that were removed simultaneously, resulting in a final diagnosis of sarcoid reaction. A review of the lymph nodes at the time of the previous uterine surgery revealed granuloma formation. Other than the presence of splenic masses, no findings suggestive of recurrence were observed in these cases. Uterine cancer and sarcoid reactions progressed without recurrence after splenectomy. Conclusions To the best of our knowledge, this is the first report of the late development of splenic sarcoid reactions after uterine cancer surgery. Sarcoid reactions and metastases are difficult to diagnose based on preoperative imaging results. However, reviewing the specimen at the time of the initial resection, the number of lesions, and the clinical findings (other than imaging findings) may aid in the determination of the correct diagnosis.

OBJECTIVES Individuals with chronic ankle instability (CAI) demonstrated altered not only ankle but also lower extremity joint angle during numerous dynamic movements compared to healthy controls. However, little is known about joint angles during sprinting, which is the most essential movement during explosive sports. We, therefore, investigated the lower extremity joint angle during sprinting between elite sprinters with CAI and healthy controls. METHODS Fourteen male college sprinters participated in this study, seven with CAI and seven healthy controls. Five-second steady speed running was performed on a treadmill at 7.5 m/s. Mean lower extremity joint angles were compared applying the statistical parametric mapping method. RESULTS The CAI patients demonstrated significantly higher ankle dorsiflexion and knee flexion angles during the stance phase. Additionally, large between-group effect sizes would demonstrate higher ankle dorsiflexion and knee and hip flexion angle from the late swing phase to the late stance phase. CONCLUSIONS The altered lower extremity joint angles from the late swing phase to the late stance phase in CAI patients suggest greater joint stability for large external loads with feed-forward motor control programs.

Abstract A 64-year-old man, who had previously undergone definitive chemoradiotherapy (dCRT) and endoscopic resections for metachronous multiple esophageal squamous cell carcinoma (ESCC) and had also received total pharyngolaryngectomy (TPL) for hypopharyngeal cancer, was diagnosed with ESCC in the middle thoracic esophagus (cT3N0M0). Thoracoscopic McKeown esophagectomy was performed for the patient. Although the tumor was tightly adherent to the thoracic duct and both main bronchi, they were successfully mobilized. In order to maintain the blood supply to the trachea, we preserved the bilateral bronchial arteries and avoided prophylactic upper mediastinal lymph node dissection. Cervical end-to-side anastomosis between the jejunum and a gastric conduit was performed. Minor pneumothorax was managed conservatively, and the patient was discharged 44 days after the surgery. Overall, thoracoscopic McKeown esophagectomy was safely performed in a patient with a history of TPL and dCRT. Surgeons should be very careful to prevent tracheobronchial ischemia by optimizing the extent of lymph node dissection.

Abstract Background In clinical studies, the EQ-5D-5L is often employed with disease-specific health-related quality of life instruments. The questions in the former are more general than the latter; however, it is known that responses to general questions can be influenced by preceding specific questions. Thus, the responses to the EQ-5D-5L have the possibility of being influenced by the preceding disease-specific health-related quality of life instruments. This may lead to bias in the cost-effectiveness analysis results. Therefore, this study aimed to evaluate the impact of the preceding cancer-specific health-related quality of life instruments on the EQ-5D-5L responses. Methods We prepared questionnaire booklets containing the EQ-5D-5L, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Functional Assessment of Cancer Therapy General with different orders. Using a quasi-randomized design, they were distributed to the patients undergoing drug therapy for advanced cancer, who were classified into three groups: Groups 1, 2, and 3 (the EQ-5D-5L placed first, second, and last, respectively). We compared the EQ-5D-5L index and the missingness of EQ-5D-5L among the groups. Results The mean EQ-5D-5L index was 0.796, 0.760, and 0.789 for groups 1 (n = 300), 2 (n = 306), and 3 (n = 331), respectively. The difference between Groups 2 and 1 was − 0.036 (95% CI − 0.065 to − 0.007; p = 0.015). The proportion of patients with an incomplete EQ-5D-5L was 0.11, 0.11, and 0.05 for Groups 1, 2, and 3, respectively. The difference of the proportions between group 3 and 1 and between 3 and 2 was − 0.06 (95% CI − 0.10 to − 0.02; p = 0.003) and − 0.06 (95% CI − 0.10 to − 0.02; p = 0.003), respectively. Conclusions Although the EQ-5D-5L index differed according to the instrument orders, the difference size would not be considerably larger than the minimally important difference. The patients tended to complete the EQ-5D-5L when they were placed at the end of the questionnaire.

American football is associated with a high risk of cervical injuries. In order to prevent these injuries, head acceleration during head impacts is currently being studied, but no studies have examined the effects on the neck. We aimed to examine the effects of head impact kinematics (the number of head impacts, maximum head linear acceleration [LA], and maximum head angular acceleration [AA]) on cervical vertebral translation (VT) in collegiate American football players over a one-year period. Twenty-two players (5 linemen and 17 skill players) who belonged to T university in the Kantoh Collegiate American Football Association Division 2. We examined the relationship between the total number of head impact kinematics over a 1-year period and the amount of cervical vertebral translation as measured by a mouth guard with a 6-axis accelerometer. The total number of head impacts of subjects was 12,368. For skill players, the 4th cervical vertebral movement distance was significantly correlated with the maximum AA (r = 0.49, P = 0.04) and also with the maximum LA (r = 0.48, P = 0.05). In Japanese collegiate American football players, it was suggested that the repeated head impacts with large maximum LA and AA generated in the head affected the amount of the 4th cervical vertebral translation. In particular, skill players were affected, so they need to develop safer tackle skills even when tackling at high speed. This may result in a decrease in acceleration during head impact, leading to a decrease in the load on the cervical spine.

Abstract Background Although conventional polymerase chain reaction (PCR) methods are widely used in diagnosis, the titer of the pathogenic virus is difficult to determine based on the PCR. In our prior report, a long-range reverse-transcription quantitative PCR (LR-RT-qPCR) assay was developed to assess the titer of UV-irradiated influenza A virus (IAV) rapidly. In this research, we focused on whether the LR-RT-qPCR assay could evaluate the titer of IAV inactivated by other methods. Methods IAV was inactivated by: heating at 100 °C for periods ranging from 1 to 15 min, treating with 0.12% sodium hypochlorite for periods ranging from 3 to 30 min, or treating with 70% ethanol for periods ranging from 10 to 30 min. Fifty percent tissue culture infectious dose (TCID50) assay was performed to confirm the efficacy of the inactivation methods, followed by LR-RT-qPCR to investigate the correlation between infectivity and copy number. Results One minute heating, 3 min sodium hypochlorite treatment, or 10 min ethanol treatment was sufficient to deactivate IAV. Changes before and after the inactivations in the copy numbers on LR-RT-qPCR were significantly different among the inactivation methods. Heat-inactivation drastically decreased the copy number to below the cutoff value around 5 copies/μL after 5 min treatment. The inactivation time of heating estimated using LR-RT-qPCR was marginally higher than that determined using TCID50. However, the treatments with sodium hypochlorite or ethanol moderately and minimally affected the copy numbers obtained using LR-RT-qPCR (~ 1 digit or no copy number decrease), respectively. Conclusions In addition to good applicability in UV-irradiation previously reported, the LR-RT-qPCR method is suitable for evaluating the effect of heat-inactivation on IAV infectivity. However, minor modifications may be made and investigated in the future to reduce the time intervals with TCID50. Although this method is not applicable for the ethanol inactivation, rapid evaluation of the effects of chlorination on IAV can be determined by comparing copy numbers before and after treatment using the LR-RT-qPCR method.

An overexpression of sialic acid is an indicator of metastatic cancer, and selective detection of sialic acid shows potential for cancer diagnosis. Boronic acid is a promising candidate for this purpose because of its ability to specifically bind to sialic acid under acidic conditions. Notably, the binding strength can be easily modulated by adjusting the pH, which allows for a simple dissociation of the bound sialic acid. In this study, we developed 5-boronopicolinic acid (5-BPA)-modified magnetic particles (BMPs) to selectively capture sialic acid biomolecules. We successfully captured fetuin, a well-known sialoglycoprotein, on BMPs at >104 molecules/particle using an acetate buffer (pH 5.0). Facile dissociation then occurred when the system was changed to a pH 7.6 phosphate buffer. This capture-and-release process could be repeated at least five times. Moreover, this system could enrich fetuin by more than 20 times. In summary, BMPs are functional particles for facile purification and concentration through the selective capture of sialic acid proteins and can improve detection sensitivity compared with conventional methods. This technology shows potential for the detection of sialic acid overexpression by biological particles.

Ti–(50−x)Ni–xFe alloys exhibit a thermally induced B2–R martensitic transformation (MT) when x is between 1.5% and 5.7%, whereas this transformation is suppressed when x is 6 at% and higher. We studied the reason for this suppression by applying compressive stress in the [110]B2 direction to single-crystalline Ti–44Ni–6Fe and Ti–42Ni–8Fe (at%) alloys. Under stress, these alloys exhibit a B2–R MT with a large temperature hysteresis of ≥50 K. The B2–R MT in these alloys is probably thermally arrested, and a small entropy change is a possible reason for this arrest. The Young’s modulus E[110] of these alloys significantly decreases with decreasing temperature, and the B2–R MT under stress occurs at a temperature where E[110] is approximately 50 GPa. Presumably, lattice softening assists the B2–R MT.

Abstract Background Economic disparities affect access to assisted reproductive technology (ART) treatment in many countries. At the time of this survey, Japan provided partial reimbursement for ART treatment only for those in low- or middle-income classes due to limited governmental budgets. However, the optimal level of financial support by income class remains unclear. Methods We conducted a conjoint analysis of ART in Japan in January 2020. We recruited 824 women with fertility problems aged 25 to 44 years via an online social research panel. They completed a questionnaire of 16 hypothetical scenarios measuring six relevant ART attributes (i.e., out-of-pocket payment, pregnancy rate, risk of adverse effects, number of visits to outpatient clinics, consultation hours and kindness of staff) and their relations to treatment choice. Results Mixed-effect logistic regression models showed that all six attributes significantly influenced treatment preferences, with participants valuing out-of-pocket payment the most, followed by pregnancy rates and kindness of staff. Significant interactions occurred between high household income (≥ 8 million JPY) and high out-of-pocket payment (≥ 500,000 JPY). However, the average marginal probability of the highest-income patients (i.e., ≥ 10 million JPY, ineligible for the subsidy) receiving ART treatment at the average cost of 400,000 JPY was 47%, compared to 56 − 61% of other income participants, who opted to receive ART at an average cost of 100,000 JPY after a 300,000 JPY subsidy. Conclusion Our results suggest that out-of-pocket payment is the primary determinant in patients’ decision to opt for ART treatment. High-income patients were more likely to choose treatment, even at a high cost, but their income-based ineligibility for government financial support might discourage some from receiving treatment.

Micro-pressure wave emission from tunnel portals in high-speed railways causes environmental issues. Tunnel hoods installed in the tunnel portals reduce the micro-pressure wave emission by reducing the pressure gradient of the compression wavefront generated in the tunnels. This study investigated the influence of the hood cross-sectional area on reducing the pressure gradient of the compression wavefront under the conditions in the current Shinkansen specifications, assuming that train running speeds would increase in the future. Scale model experiments were conducted using axisymmetric cross-section models of the tunnel, hoods, and trains; the high-speed train model was launched into the tunnel and hood models. The effect of the hood on the reduction of the micro-pressure wave was estimated by measuring the pressure gradient of the compression wavefront generated in the tunnel model. The experimental results show that the effect of the hoods depends on their length and cross-sectional area, even if there are apertures on the sidewall of the hoods. Furthermore, when there are no side apertures on the hoods and the cross-section is longitudinally uniform, the optimum hood cross-sectional area at which the maximum pressure gradient of the compression wavefront is the lowest depends on the train speed and nose length. The findings of this study will provide useful insights into the structural design of tunnel hoods in high-speed railways.

Whether or not conditions should be included in publicly funded newborn screening (NBS) programs should be discussed according to objective and transparent criteria. Certain criteria have been developed for the introduction of NBS programs in the context of individual countries; however, there are no standard selection criteria for NBS programs in Japan. This study aimed to develop a quantitative scoring model to assess newborn screening that incorporates the views of a variety of stakeholders in Japan. The five recommended eligibility criteria for NBS were stratified based on previous studies and expert opinions, using the analytic hierarchy process. We conducted a cross-sectional, web-based questionnaire targeting a wide range of people involved in NBS to investigate pairwise comparisons of the evaluation items between February and April of 2022. There were 143 respondents. Most of our respondents (44.1%) were physicians. Fifty-eight respondents (40.6%) had been engaged in NBS-related research or work for more than 10 years. The distribution of allocation points was the highest for ‘intervention’, ‘screening test’, ‘follow-up setting’, ’economic evaluation’, and ’disease/condition’, in that order. The algorithm in this study will guide decision makers in collecting and evaluating objective data, thus enabling transparent discussions to occur.

Various viral diseases can be widespread and cause severe disruption to global society. Highly sensitive virus detection methods are needed to take effective measures to prevent the spread of viral infection. This required the development of rapid virus detection technology to detect viruses at low concentrations, even in the biological fluid of patients in the early stages of the disease or environmental samples. This review describes an overview of various virus detection technologies and then refers to typical technologies such as beads-based assay, digital assay, and pore-based sensing, which are the three modern approaches to improve the performance of viral sensing in terms of speed and sensitivity.

Abstract Background Hybrid emergency room (ER) systems, consisting of an angiography-computed tomography (CT) machine in a trauma resuscitation room, are reported to be effective for reducing death from exsanguination in trauma patients. We aimed to investigate the cost-effectiveness of a hybrid ER system in severe trauma patients without severe traumatic brain injury (TBI). Methods We conducted a cost-utility analysis comparing the hybrid ER system to the conventional ER system from the perspective of the third-party healthcare payer in Japan. A short-term decision tree and a long-term Markov model using a lifetime time horizon were constructed to estimate quality-adjusted life years (QALYs) and associated lifetime healthcare costs. Short-term mortality and healthcare costs were derived from medical records and claims data in a tertiary care hospital with a hybrid ER. Long-term mortality and utilities were extrapolated from the literature. The willingness-to-pay threshold was set at $47,619 per QALY gained and the discount rate was 2%. Deterministic and probabilistic sensitivity analyses were conducted. Results The hybrid ER system was associated with a gain of 1.03 QALYs and an increment of $33,591 lifetime costs compared to the conventional ER system, resulting in an ICER of $32,522 per QALY gained. The ICER was lower than the willingness-to-pay threshold if the odds ratio of 28-day mortality was < 0.66. Probabilistic sensitivity analysis indicated that the hybrid ER system was cost-effective with a 79.3% probability. Conclusion The present study suggested that the hybrid ER system is a likely cost-effective strategy for treating severe trauma patients without severe TBI.

Abstract Background To develop direct and indirect (response) mapping algorithms from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy General (FACT-G) onto the EQ-5D-5L index. Methods We conducted the QOL-MAC study where EQ-5D-5L, EORTC QLQ-C30, and FACT-G were cross-sectionally evaluated in patients receiving drug treatment for solid tumors in Japan. We developed direct and indirect mapping algorithms using 7 regression methods. Direct mapping was based on the Japanese value set. We evaluated the predictive performances based on root mean squared error (RMSE), mean absolute error, and correlation between the observed and predicted EQ-5D-5L indexes. Results Based on data from 903 and 908 patients for EORTC QLQ-C30 and FACT-G, respectively, we recommend two-part beta regression for direct mapping and ordinal logistic regression for indirect mapping for both EORTC QLQ-C30 and FACT-G. Cross-validated RMSE were 0.101 in the two methods for EORTC QLQ-C30, whereas they were 0.121 in two-part beta regression and 0.120 in ordinal logistic regression for FACT-G. The mean EQ-5D-5L index and cumulative distribution function simulated from the recommended mapping algorithms generally matched with the observed ones except for very good health (both source measures) and poor health (only FACT-G). Conclusions The developed mapping algorithms can be used to generate the EQ-5D-5L index from EORTC QLQ-C30 or FACT-G in cost-effectiveness analyses, whose predictive performance would be similar to or better than those of previous algorithms.

We investigate the causal relationship between financial development and economic growth―the finance-growth nexus―in Brazil, India, Philippines, Thailand, and Turkey by controlling for the globalization indicators of trade openness, foreign direct investment (FDI), and portfolio investment, together with the structural break dummy. Our sample countries of different regions have various experiences of developing and liberalizing their financial systems and external sectors as well as financial crises. Time series data span over the period 1974-2017, and two financial indicators of size and efficiency are used in estimation. Implementing the cointegration and Granger causality tests in the framework of the vector error correction model (VECM), we find that: 1) financial size and economic growth are in a positive, bilateral relationship in all the sample countries, although that of Turkey is more inclining toward economic growth causing financial size; 2) when financial development is proxied by financial efficiency, the results are different among the five countries; and 3) although theoretically expected to be contributive, the globalization indicators of trade openness, FDI, and portfolio investment exhibit either a positive or negative impact on financial development and economic growth. Based on empirical findings, we argue that policy-makers should design and develop financial sector polices and growth strategies fully considering the nature of their countries’ own institutional and structural characteristics.

Abstract Background The polymerase chain reaction (PCR) is commonly used to detect viral pathogens because of its high sensitivity and specificity. However, conventional PCR methods cannot determine virus infectivity. Virus infectivity is conventionally examined with methods such as the plaque assay, even though such assays require several days. Long-range reverse-transcription quantitative PCR (RT-qPCR) has previously been suggested for the rapid assessment of RNA virus infectivity where the loss of infectivity is attributable to genomic fragmentation. Methods IAV was irradiated with 253.7 nm ultraviolet (UV) rays to induce genomic strand breaks that were confirmed by a full-length RT-PCR assay. The IAV was then subjected to plaque assay, conventional RT-qPCR and long-range RT-qPCR to examine the relationship between infectious titer and copy number. A simple linear regression analysis was performed to examine the correlation between the results of these assays. Results A long-range RT-qPCR assay was developed and validated for influenza A virus (IAV). Although only a few minutes of UV irradiation was required to completely inactivate IAV, genomic RNA remained detectable by the conventional RT-qPCR and the full-length RT-PCR for NS of viral genome following inactivation. A long-range RT-qPCR assay was then designed using RT-priming at the 3′ termini of each genomic segment and subsequent qPCR of the 5′ regions. UV-mediated IAV inactivation was successfully analyzed by the long-range RT-qPCR assay especially when targeting PA of the viral genome. This was also supported by the regression analysis that the long-range RT-qPCR is highly correlated with plaque assay (Adjusted R 2 = 0.931, P = 0.000066). Conclusions This study suggests that IAV infectivity can be predicted without the infectivity assays. The rapid detection of pathogenic IAV has, therefore, been achieved with this sensing technology.

Increased strain of the iliotibial band (ITB) is a key factor of ITBS aggravation. There are several internal risk factors contributing to increased ITB strain; gender (female), knee malalignment (genu varum > genu valgus), deteriorated muscle strength and/or muscle activation. However, running biomechanics as an inciting movement of ITBS should be included in the clarification of the ITBS mechanism. The purpose of this study was to clarify the change of the ITB strain during running and to identify differences in muscle activity between runners with or without genu varum. A total of 17 healthy recreational women runners [genu varum group (GV) = 8; normal group (N) = 9] volunteered in this study. Participants performed 30 minutes of running, and muscle activity of gluteus maximus (GMAX), gluteus medius (GMED), and tensor fascia latae (TFL) were recorded every 10 minutes of the running. Before and after running, the strain of the ITB and hip muscle strength were measured. The results showed a significantly increased ITB strain in standing after 30-min running for the participants with genu varum alignment. Also, there was a significant difference between the groups. And the muscle activities of the TFL and GMAX in the GV group were greater than those in the N group. These findings indicate that genu varum alignment may induce more tensile stress on the ITB as a result of greater activation of the TFL during running, thus increasing the strain of the ITB.

Abstract Background The Health Utilities Index Mark 3 (HUI3) is a generic multi-attribute, preference-based system for assessing health-related quality of life. It is widely used overseas as an outcome measure and for estimating quality-adjusted life years. We aimed to estimate a multi-attribute and eight single-attribute utility functions for the HUI3 system based on community preferences in Japan. We conducted two preference surveys in this study. The first survey was designed to estimate a model of utility function and collect preference scores, and the second survey was designed to evaluate predictive validity of the utility function and provide independent scores. Values obtained from the feeling thermometer and standard gamble scores obtained from using a chance board were included in the preference scale. We recruited 1043 respondents (age: 20–79 years) from five cities in Japan through the general population classified by sex and age groups. Respondents were further randomly divided into a modeling group (n = 774) and a direct group (n = 263). Results We acquired the estimation for eight single-attribute and a global multi-attribute utility function. The minimum expected multi-attribute utility score was − 0.002. The intraclass correlation coefficient between the directly measured utility score and the score generated by multi-attribute function in terms of 53 health conditions was 0.742. Conclusions The HUI3 scoring function developed in Japan has a strong theoretical and empirical basis. It will be useful in future to predict the directly measured score of health technology assessments in Japan.

This study investigates Mexico’s finance-growth nexus by controlling the “globalization” variables of trade openness, foreign direct investment (FDI) and portfolio investment together with the structural break dummy. Financial development is proxied by two indicators of size and efficiency. Implementing the cointegration and Granger causality tests in the framework of the vector error correction model (VECM), we found that: financial size is negative for economic growth with no feedback; financial efficiency and economic growth are in a negative bilateral relationship; trade openness and portfolio investment are positive for economic growth; and FDI is negative for economic growth and financial efficiency.

The purpose of this study was to analyze head impact kinematics at different locations of Japanese university American football players using a 6DOF (degrees of freedom) device. The subjects of this study were 43 players who belonged to T University in the Kanto Collegiate American Football Association second division. We used a Vector Mouthguard (i1 Biometrics Inc.) equipped with a 6DOF to measure the head LA (linear acceleration), AA (angular acceleration) and AV (angular velocity), as well as the number of head impacts during collisions, and evaluated 4 impact locations (front, side, back, and top) in detail. The total number of head impacts was 2,070 during games and 10,007 during practice sessions for a total of 7 games and 41 practices during fall regular seasons over a 2-year period. The most common head impact location was the front (43.5%), followed by the side (41.9%), top (10.9%), and back (3.7%). When classifying the total number of head impacts at these locations according to player position, skill players showed the highest proportion of side impacts (p < 0.05), whereas linemen showed the highest proportion of frontal impacts (p < 0.05) compared to the other locations. These results support previous studies conducted for university American football players in the United States. That is, the frequency and location of head impacts is greatly influenced by player position. Regarding the magnitude of head impact locations, the LA and AA values for back of the head impacts were the highest both at games and practice sessions. In addition, the AA value for impacts to the top of the head was much higher than the AA value for impacts to the front and side (p < 0.05). Also, there were significant positive correlations between peak LA and peak AA at all head impact locations for games and practice sessions based on player position (p < 0.05). Skill players showed significant positive correlations between peak AA and peak AV at all head impact locations in games (p < 0.05). In comparison, linemen showed significant positive correlations between peak AA and peak AV for frontal and side impacts for games and frontal, side, and top of head impacts in practice sessions (p < 0.05). As a result, it was clear that Japanese university American football players could not stabilize the head during collisions. In conclusion, it was found that the frequency of head impact locations in Japanese university American football players was the same as that in the USA. In head impact kinematics during collisions, Japanese university American football players showed different characteristics from their American counterparts. In the future, we should take into account neck muscular strength and motion analysis to better understand the influence of head impacts on Japanese university American football players.

From the viewpoint of resource and energy-saving, the high extraction rate of alternating liquid–liquid flow (slug flow) is important given that it enables its novel use in extraction. Additionally, a specific extraction rate must be maintained for the practical application of slug flow to chemical extraction. Although slug flow is easily generated, controlling the slug length is difficult. In this study, two diaphragm pumps were interlocked to generate a slug flow. By linking the movement of the diaphragms of the two pumps, we could successfully and efficiently control the slug length, and the interlocking diaphragms could easily control the length of the aqueous and oil phase segments of the slug flow. The lengths of the aqueous and oil phases of the slug flow, which could not be quantitatively controlled, could be expressed in terms of the linear velocity of the liquid, the kinematic viscosity, and the tube diameter using the Reynolds number. This relation aids the extraction equipment design using slug flow. Furthermore, the mass transfer coefficient of extraction obtained using the slug flow generated by the developed device was similar to that obtained by the conventional method of a syringe pump. These results indicate that slug flow can be successfully applied to extraction processes.

We conducted a theoretical investigation of the cross-sectional aspect ratio of a rectangular channel to have sufficiently low frictional resistance under less than 150 of the Reynolds number. From the theoretical consideration, it was clarified that 3.40 or more is recommended as a criterion for determining the aspect ratio. This addresses the problem of determining the interval of rectangle channels, installed in a plate reactor. There is a concern that the real system does not follow the analytical solution, assuming laminar flow, since the higher aspect ratio leads to disturbances of the flow such as the emergence of vortices. However, in the channel’s volume range of (W × H × L) = (7.0 mm × 0.38 mm × 0.26 m), such a turbulence was not observed in the detailed numerical calculation by CFD, where both calculation results were in agreement to within 3% accuracy. Moreover, even in an experimental system with a surface roughness of ca. 7%, friction resistance took agreement within an accuracy of ±30%.

Abstract Background This study evaluated the cost-effectiveness of replacing standard intravenous therapy (taxane) with oral S-1 therapy for first-line metastatic breast cancer treatment. Methods This cost-effectiveness analysis was based on data from a randomized phase III trial (SELECT BC). As cost-effectiveness was a secondary endpoint of the SELECT BC trial, some of the randomized patients participated in an EQ-5D survey (N = 391) and health economic survey (N = 146). The EQ-5D responses, claims, and prescription data were collected for as long as possible until death. The expected quality-adjusted life years (QALY) obtained from each treatment were calculated using patient-level EQ-5D data, and the expected cost was calculated using patient-level claim data. The analysis was performed from the perspective of public healthcare payers. Results The estimated EQ-5D least-square means and 95% CI up to 48 months were 0.764 (95% CI, 0.741–0.782) and 0.742 (95% CI, 0.720–0.764) in the S-1 and taxane arms, respectively. The expected QALY was 2.11 for the S-1 arm and 2.04 for the taxane arm, with expected costs of JPY 5.13 million (USD 46,600) and JPY 5.56 million (USD 50,500), respectively. These results show that S-1 is cost-saving. According to probabilistic sensitivity analysis, S-1 was dominant with a probability of 63%. When the willingness to pay (WTP) value was JPY 5 million (USD 45,500) per QALY, the probability of being cost-effective was 92%. Conclusions Our results show that the introduction of oral S-1 therapy for metastatic breast cancer is highly likely to be cost-effective. Trial registration UMIN CTR C000000416 . Registered on May 10, 2006.

The aim of this study is to understand the head impact during actual collisions between American football players from Japanese universities. The subjects of this study were 23 players who belonged to T university in the Kantoh Collegiate American Football Association Division 2. We used a Vector Mouthguard (i1 Biometrics Inc.) equipped with 6 degrees of freedom (DOF) to measure the head linear acceleration (LA) and rotational acceleration (RA) as well as the head injury criterion (HIC), impact location, and number of impacts during collisions. The average number of collisions per player during a practice and during a game was 14.3 and 15.7, respectively. In terms of positions, the ratio (1:1.3) of total number of impacts for backs to linemen in Japan is lower than that (1:3) in the USA. Both during the games and practices, the range of 10 g < X ≤ 15 g in the average peak LA values was the most frequent, and the distributions were largely skewed toward low values (p < 0.05). The medians during the games and practices were 16.77 g and 15.87 g, respectively. The number of collisions during practices in Japan was significantly higher than that in the USA. Particularly, linemen undergo more head collisions than those of backs. Another common factor is that the impact of head collision during a game is significantly higher than that during a practice. However, data on Japanese university players is limited, and further data collection should be done before determining an accurate estimate of the practical concussion risk threshold.

Incretin therapy has emerged as one of the most popular medications for type 2 diabetes. We have previously reported that the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin attenuates neointima formation after vascular injury in non-diabetic mice. In the present study, we examined whether combined treatment with linagliptin and the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin attenuates neointima formation in diabetic mice after vascular injury. Diabetic db/db mice were treated with 3 mg/kg/day linagliptin and/or 30 mg/kg/day empagliflozin from 5 to 10 weeks of age. Body weight was significantly decreased by empagliflozin and the combined treatment. Blood glucose levels and glucose tolerance test results were significantly improved by empagliflozin and the combined treatment, but not by linagliptin. An insulin tolerance test suggested that linagliptin and empagliflozin did not improve insulin sensitivity. In a model of guidewire-induced femoral artery injury in diabetic mice, neointima formation was significantly decreased in mice subjected to combined treatment. In an in vitro assay using rat aortic smooth muscle cells (RASMC), 100, 500, or 1000 nM empagliflozin significantly decreased the RASMC number in a dose-dependent manner. A further significant reduction in RASMC proliferation was observed after combined treatment with 10 nM linagliptin and 100 nM empagliflozin. These data suggest that combined treatment with the DPP-4 inhibitor linagliptin and SGLT2 inhibitor empagliflozin attenuates neointima formation after vascular injury in diabetic mice in vivo and smooth muscle cell proliferation in vitro. Keywords: DPP-4I, SGLT2I, Neointima formation, VSMC proliferation

Multi-drug resistance of pathogenic microorganisms is becoming a serious threat, particularly to immunocompromised populations. The high mortality of systematic fungal infections necessitates novel antifungal drugs and therapies. Unfortunately, with traditional drug discovery approaches, only echinocandins was approved by FDA as a new class of antifungals in the past two decades. Drug efflux is one of the major contributors to multi-drug resistance, the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug resistance. In this study, we combined structure-based virtual screening and whole-cell based mechanism study, identified a natural product, beauvericin (BEA) as a drug efflux pump modulator, which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette (ABC) transporters; meantime, BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species (ROS). It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole (KTC) and could cure the murine model of disseminated candidiasis. Toxicity evaluation of BEA, including acute toxicity test, Ames test, and hERG (human ether-à-go-go-related gene) test promised that BEA can be harnessed for treatment of candidiasis, especially the candidiasis caused by ABC overexpressed multi-drug resistant C. albicans.

The population is aging rapidly in many developed countries. Such countries need to respond to the growing demand and expanding costs of healthcare (HC) for the elderly. Therefore, it is important to investigate the factors correlating such HC costs. In Japan, HC is composed of two sections, namely medical care (MC) and long-term care (LTC). While many studies have examined MC and LTC costs on their own, few studies have conducted comprehensive investigations of HC costs. The aim of this study is to examine the risk factors that influence HC costs for the elderly who enroll in the LTC insurance system in Japan.The inclusion criteria in the present study are as follows: being 65 years of age, or older; certified eligibility for, and use of services offered by the LTC insurance system at home or in an institutional setting in December 2009; and being covered by the National Health Insurance (NHI) system. MC and LTC insurance data were obtained from claim records for the elderly in July and December of 2007, 2008, and 2009 (i.e., a total of six survey points). Panel data, per subject, were constructed using MC and LTC claim records. The sample included 810 subjects and 4029 observations.We estimated a regression equation with a censored dependent variable using a Tobit model. Significant associations between MC or LTC costs and interaction terms (household composition × seasonal effects) were investigated. MC costs significantly decreased and LTC costs significantly increased among subjects living alone during winter. Income level was also a positive determinant of MC costs, while eligibility level was a positive determinant of LTC costs.We recommend that the health policy for the elderly focus more on seasonal effects, household composition, and income level, as well as on eligibility level.

OBJECTIVE:To compare radical surgery with definitive chemoradiation (CRT) for esophageal squamous cell carcinoma using propensity score (PS) matching at our single institution. MATERIALS AND METHODS:A total of 386 consecutive, surgically treated and 243 CRT-treated cases between 2001 and 2014 were analyzed. PS was calculated using multivariable analysis (logistic regression) for pairs of variables such as treatment time, age, sex, primary tumor location, clinical stage, and clinical T- and N-stage for patients after excluding clinical T4 and M1 cases. According to PS, 133 surgically-treated and 134 CRT-treated cases were selected randomly by software. RESULTS:The patients' median age was 68 years in the CRT group and 71 years in the surgery group. Clinical stage II-III, T3, N0 (according to the 7th American Joint Committee on Cancer-2009), and upper plus middle thoracic esophageal disease were seen in 68%, 44%, 54%, and 59%, respectively, in the CRT group and 64%, 47%, 55%, and 64%, respectively, in the surgery group. The 3- and 5-year overall survival was 47.1% and 34.0% in the CRT group and 68.3% and 54.4% in the surgery group (p = 0.0019). The 3- and 5-year progression-free survival was 45.3% and 38.8% in the CRT group and 61.1% and 54.4% in the surgery group (p = 0.022). CONCLUSION:CRT may be inferior to surgery in survival, although a selection bias for patients selected for a non-operative approach cannot be excluded, especially since surgery is the standard of care at this institution. A prospective randomized clinical trial will be necessary to draw a definite conclusion.

In this paper, shift multiplex recording of phase data pages on a volume polarization-sensitive medium by retardagraphy is demonstrated. The origin of shift selectivity in volume retardagraphy is explained. In the experiment, four-valued phase data pages are used. Then, a coding method is proposed to correct a reconstructed phase pattern. The recorded phase data pages are reconstructed using the feature of the coding method. By comparing the reconstructed phase data pages with recording phase data pages, symbol error rates of less than 11% are achieved. From the experimental result, it is verified that volume retardagraphy is applicable to optical memory.

Random phase masks are important technical elements for realizing holographic memory systems that enable high density recording. However, the broadly distributed Fourier spectrum often presents a problem because wide recording spots result in reduced total storage capacity for a recording medium. In the present study, we propose modified random phase masks with phase modulation elements exhibiting Gaussian profiles to suppress the spread of the recording spot and keep it in a narrow area, based on the reduction of the high-frequency components in a random phase pattern. We confirm the effectiveness of the proposed random phase mask using simulations of a computer-generated binary hologram. However, issues still remain in terms of the fabrication of random phase masks with Gaussian profiles. Therefore, we evaluate the feasibility of fabricating the proposed random phase mask using molecular diffusion under photopolymerization. The results confirm the feasibility of this approach over a relatively wide area for actual fabrication.

A high-speed train entering a tunnel generates a compression wave that propagates through the tunnel toward its exit. When the compression wave reaches the tunnel exit, a pressure pulse causing environmental problems (the micro-pressure wave) is radiated from the exit portal. The micro-pressure wave magnitude is approximately proportional to the maximum pressure gradient of the tunnel compression wave arriving at the exit portal. In a long Shinkansen tunnel with concrete slab tracks, the compression wavefront steepens due to the nonlinear effect during its propagation because all surfaces of the tunnel wall are smooth. Therefore, it is necessary to investigate the compression wave distortion in a tunnel and to clarify the characteristics of the compression wave propagation for estimating and reducing the magnitude of the micro-pressure wave. In this paper, we introduce a new simple equation governing distortion of the tunnel compression wave propagating through a Shinkansen tunnel with concrete slab-tracks. We propose a new simple scheme for numerical calculations. A space evolution type equation with one variable is derived from the three conservation equations (mass, momentum, and energy including the wall friction and heat transfer terms) of the 1D CFD by assuming small disturbances excited by the compression wave. The numerical calculation scheme based on the simple equation reduces the computing time remarkably because its CFL condition is relaxed. The calculation results obtained using the proposed scheme agree well with those by a conventional scheme based on the 1D CFD. The accuracy of the simple equation is verified.

Aryl hydrocarbon receptor interacting protein (AIP) is thought to be a tumor suppressor gene, as indicated by a mutational analysis of pituitary somatotroph adenomas. However, the physiological significance of AIP inactivation in somatotroph cells remains unclear. Using CRISPR/Cas9, we identified a GH3 cell clone (termed GH3-FTY) in which Aip was genetically disrupted, and subsequently investigated its character with respect to growth hormone (Gh) synthesis and proliferation. Compared with GH3, GH3-FTY cells showed remarkably increased Gh production and a slight increase in cell proliferation. Gh-induced Stat3 phosphorylation is known to be a mechanism of Gh oversecretion in GH3. Interestingly, phosphorylated-Stat3 expression in GH3-FTY cells was increased more compared with GH3 cells, suggesting a stronger drive for this mechanism in GH3-FTY. The phenotypes of GH3-FTY concerning Gh overproduction, cell proliferation, and increased Stat3 phosphorylation were significantly reversed by the exogenous expression of Aip. GH3-FTY cells were less sensitive to somatostatin than GH3 cells in the suppression of cell proliferation, which might be associated with the reduced expression of somatostatin receptor type 2. GH3-FTY xenografts in BALB/c nude mice (GH3-FTY mice) formed more mitotic somatotroph tumors than GH3 xenografts (GH3 mice), as also evidenced by increased Ki67 scores. GH3-FTY mice were also much larger and had significantly higher plasma Gh levels than GH3 mice. Furthermore, GH3-FTY mice showed relative insulin resistance compared with GH3 mice. In conclusion, we established a somatotroph cell line, GH3-FTY, which possessed prominent Gh secretion and mitotic features associated with the disruption of Aip.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues. A constitutively activated mutation of a bone morphogenetic protein (BMP) receptor, ALK2, has been identified in patients with FOP. We report here that four structurally related compounds, lucilactaene, hydroxylucilactaene, NG-391 and NG-393, produced by fungal strain Fusarium sp. B88, inhibit BMP signaling in vitro. Alkaline phosphatase activity, a marker enzyme of osteoblastic differentiation, was decreased in C2C12 myoblasts stably expressing mutant ALK2 by treatment with those compounds with IC50 values of 5.7, 6.8, 6.9 and 6.1 μM, respectively. Furthermore, NG-391 and NG-393 inhibited BMP-specific luciferase reporter activity, which is directly regulated by transcription factor Smads, with IC50 values of 1.4 and 2.1 μM, respectively. These findings suggest that these fungal metabolites may provide a new direction in the development of FOP therapeutics.

Photocontrol of molecular alignment is an exceptionally-intelligent and useful strategy. It enables us to control optical coefficients, peripheral molecular alignments, surface relief structure, and actuation of substances by means of photoirradiation. Azobenzene-containing polymers and functionalized liquid crystalline polymers are well-known photocontrollable materials. In this paper, we introduce recent applications of these materials in the fields of mechanics, self-organized structuring, mass transport, optics, and photonics. The concepts in each application are explained based on the mechanisms of photocontrol. The interesting natures of the photocontrollable materials and the conceptual applications will stimulate novel ideas for future research and development in this field.

Low-temperature water-gas shift reaction (WGS) using gold catalyst is expected to be an attractive technique to realize an efficient on-site hydrogen production process. In this paper, Au/Fe3O4 catalysts for promoting the WGS below 150 °C were developed by a preliminary reduction of Au/iron oxide (Fe3+) catalyst utilizing high reactivity of Au nano-particles. The reduction was conducted under a CO, H2, or CO/H2O stream at either 140 or 200 °C, and the effect of reduction conditions on the characteristics of the Au/Fe3O4 catalyst and on the catalytic activity in WGS at 80 °C was investigated. The reaction progress during the pre-reduction treatment was qualitatively analyzed, and it was found that the iron oxide in Au/Fe2O3 calcined at 200 °C was easily reduced to Fe3O4 phase in all reduction conditions. The reduction conditions affected the characteristics of both Au and iron oxide, but all of the reduced catalysts had small Fe3O4 particles of less than 20 nm with Au particles on the surface. The surface area and content of cationic Au were high in the order of CO, H2, CO/H2O, and 140, 200 °C. In the WGS test at 80 °C using the developed catalysts, the activities of the catalysts pre-reduced by CO at 140 or 200 °C and by H2 at 140 °C were very high with 100% CO conversion even at such a low temperature. These results indicated that factors such as higher surface area, crystallized Fe3O4, and cationic Au content contributed to the catalytic activity.

We have investigated the relation between the softening of elastic constants and martensitic transformation in Fe3Pt, which exhibits various kinds of martensitic transformation depending on its long-range order parameter S. The martensite phases of the examined alloys are BCT (S = 0.57), FCT1 (S = 0.75, c/a < 1) and FCT2 (S = 0.88, c/a > 1). The elastic constants C′ and C44 of these alloys decrease almost linearly with decreasing temperature. Although the temperature coefficient of C′ decreases as S increases, C′ at the transformation temperature is the smallest in the alloy with S = 0.75, which transforms to FCT1. This result implies that softening is most strongly related to the formation of the FCT1 martensite with tetragonality c/a < 1 among the three martensites.

When a train travels through a tunnel at high speed, large pressure variations are generated in the tunnel. They impose loads on tunnel lining, equipment inside the tunnel, and the train. It is thus necessary to accurately estimate these pressure variations in order to specify the design loads for them. Model experiments are effective in investigating these pressure variations. In the model experiments, we have used axisymmetric train models, because the train model is launched by friction drive consisting of some pairs of vertically aligned wheels. However, the experiments using axisymmetric train models can not accurately simulate the pressure variations in the area close to the passing train. Therefore, we have developed a launcher which can shoot an actual shape train model at the maximum speed of 250km/h by rotating wheels, and performed model experiments using both the actual shape models and the axisymmetric models. The results show that the pressure variations in the area close to the train using actual shape train model and actual shape tunnel model agree well with those of field measurements, and the magnitude of the pressure variations is inversely proportional to a square of an observation distance. Furthermore, the results have been verified by an acoustic analysis.

This paper proposes a novel weighting algorithm for Cross-power Spectrum Phase (CSP) analysis to improve the accuracy of direction of arrival (DOA) estimation for beamforming in a noisy environment. Our sound source is a human speaker and the noise is broadband noise in an automobile. The harmonic structures in the human speech spectrum can be used for weighting the CSP analysis, because harmonic bins must contain more speech power than the others and thus give us more reliable information. However, most conventional methods leveraging harmonic structures require pitch estimation with voiced-unvoiced classification, which is not sufficiently accurate in noisy environments. In our new approach, the observed power spectrum is directly converted into weights for the CSP analysis by retaining only the local peaks considered to be harmonic structures. Our experiment showed the proposed approach significantly reduced the errors in localization, and it showed further improvements when used with other weighting algorithms.