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The presence of a JAK2 V617F or JAK2 exon 12 mutation is one of the three major criteria listed for the diagnosis of polycythemia vera (PV) in the 2017 World Health Organization Classification. However, a nationwide study has not yet been conducted in Japan since the discovery of JAK2 mutations. Therefore, the Japanese Society of Hematology (JSH) retrospectively analyzed the clinical characteristics of 596 Japanese patients with PV diagnosed between April 2005 and March 2018. Among the 473 patients with complete data on JAK2 mutations available, 446 (94.3%) and 10 (2.1%) were positive for the JAK2 V617F and JAK2 exon 12 mutations, respectively. During a median follow-up of 46 months (range: 0-179 months), 47 (7.9%) deaths occurred. The major causes of death were secondary malignancies (23.4%), acute leukemia (12.8%), non-leukemic progressive disease (10.6%) and thrombotic (6.4%) and hemorrhagic complications (6.4%). Thrombotic and hemorrhagic events occurred during the clinical course in 4.0% (n = 24) and 3.5% (n = 21) of patients, respectively. These results show that the international PV prognostic score (age, venous thrombosis and leukocytosis) is applicable to Japanese patients with PV.

Re-irradiation of a previously irradiated site must be done with careful consideration to minimize dose to organs at risk.To evaluate pain response and safety of Sr-89 administration for painful bone metastases after prior irradiation.We retrospectively reviewed patients with Sr-89 injection for painful bone metastasis in a previously irradiated site. All patients were seen in follow-up at 1, 2, 3, and 4 months after injection and every 6 months thereafter. Pain control, toxicity, and pain progression-free survival were analyzed. Correlation of pain relapse with the following characteristics was analyzed: gender, age, primary tumor, tumor pathology, baseline performance status, and baseline verbal rating scale.Among 25 patients analyzed (10 male, 15 female), median age was 68 (range, 50-81) years. Primary tumor sites included lung (n = 11), breast (n = 3), uterine cervix (n = 3), prostate (n = 3), and others (n = 5). Median follow-up was 25 (range, 1-76) months. Pain relief was observed in 24 patients (96.0%). One- and 2-year pain progression-free survival rates in these patients were 54.5% and 48.4%, respectively. Median time to pain progression was 5 (range, 2-16) months. Statistically significantly lower pain progression-free survival was observed in patients with osteolytic bone metastases (p 0.01). No grade 3 or worse adverse events were observed.Sr-89 injection showed pain relief in most of our patients with painful bone metastases in a previously irradiated site and caused no grade 3 or worse adverse events. Sr-89 is an option for patients with a painful bone metastasis in a previously irradiated site.

This study is an international multi-institutional retrospective study comparing the clinical outcomes between intracavitary brachytherapy (ICBT) and the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients treated with definitive radiation therapy. Locally advanced cervical cancer, the initial size of which is larger than 4 cm and treated by concurrent chemoradiotherapy and image-guided adaptive brachytherapy, were eligible for this retrospective study. Patients who received HBT at least once were included in the HBT group, and patients who received only ICBT were included in the ICBT group. Anonymized data from 469 patients from 13 institutions in Japan, one from Korea and one from Thailand, were analyzed. Two hundred eighty and 189 patients were included in the ICBT group and the HBT group, respectively. Patients in the HBT group had more advanced stage, non-Scc histopathology, a higher rate of uterine body involvement, larger tumor at diagnosis, larger tumor before brachytherapy and a lower tumor reduction ratio. With a median follow-up of 51.3 months (2.1–139.9 months), 4-y local control (LC), progression-free survival (PFS) and overall survival (OS) for the entire patient population were 88.2%, 64.2% and 83%, respectively. The HBT group received a higher HR-CTV D90 than that of the ICBT group (68.8 Gy vs 65.6 Gy, P = 0.001). In multivariate analysis, the non-Scc histological subtype, HR-CTV D95 ≤ 60 Gy, reduction ratio ≤ 29% and total treatment time (TTT) ≥ 9 weeks were identified as the independent adverse prognostic factors for LC. Regarding LC, no difference was found between ICBT and HBT (4-y LC 89.3% vs 86.8%, P = 0.314). After adjustment for confounding factors by propensity score matching, no advantage of applying HBT was demonstrated regarding LC, PFS, or OS. Despite the fact that HBT patients had more adverse clinical factors than ICBT patients, HBT delivered a higher dose to HR-CTV and resulted in comparable LC.

This study is an international multi-institutional retrospective study comparing the clinical outcomes between intracavitary brachytherapy (ICBT) and the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients treated with definitive radiation therapy. Locally advanced cervical cancer, the initial size of which is larger than 4cm and treated by concurrent chemoradiotherapy and image-guided adaptive brachytherapy, were eligible for this retrospective study. Patients who received HBT at least once were included in the HBT group, and patients who received only ICBT were included in the ICBT group. Anonymized data from 469 patients from 13 institutions in Japan, one from Korea and one from Thailand, were analyzed. Two hundred eighty and 189 patients were included in the ICBT group and the HBT group, respectively. Patients in the HBT group had more advanced stage, non-Scc histopathology, a higher rate of uterine body involvement, larger tumor at diagnosis, larger tumor before brachytherapy and a lower tumor reduction ratio. With a median follow-up of 51.3months (2.1-139.9months), 4-y local control (LC), progression-free survival (PFS) and overall survival (OS) for the entire patient population were 88.2%, 64.2% and 83%, respectively. The HBT group received a higher HR-CTV D90 than that of the ICBT group (68.8Gy vs 65.6Gy, P = 0.001). In multivariate analysis, the non-Scc histological subtype, HR-CTV D95 ≤ 60Gy, reduction ratio ≤ 29% and total treatment time (TTT) ≥ 9weeks were identified as the independent adverse prognostic factors for LC. Regarding LC, no difference was found between ICBT and HBT (4-y LC 89.3% vs 86.8%, P = 0.314). After adjustment for confounding factors by propensity score matching, no advantage of applying HBT was demonstrated regarding LC, PFS, or OS. Despite the fact that HBT patients had more adverse clinical factors than ICBT patients, HBT delivered a higher dose to HR-CTV and resulted in comparable LC.

Objective: Intensity-modulated radiotherapy (IMRT) is a well-established radiotherapy technique for delivering radiation to cancer with high conformity while sparing the surrounding normal tissue. Two main purposes of this study are: (1) to investigate dose calculation accuracy of helical IMRT (HIMRT) and volumetric-modulated arc therapy (VMAT) on surface region and (2) to evaluate the dosimetric efficacy of HIMRT and VMAT for scalp-sparing in whole brain radiotherapy (WBRT). Methods: First, using a radiochromic film and water-equivalent phantom with three types of boluses (1, 3, 5 mm), calculation/measurement dose agreement at the surface region in the VMAT and HIMRT plans were examined. Then, HIMRT, 6MV-VMAT and 10MV-VMAT with scalp-sparing, and two conventional three-dimensional conformal radiotherapy plans (6MV-3DCRT and 10MV-3DCRT; as reference data) were created for 30 patients with brain metastasis (30 Gy/10 fractions). The mean dose to the scalp and the scalp volume receiving 24 and 30 Gy were compared. Results: The percentage dose differences between the calculation and measurement were within 7%, except for the HIMRT plan at a depth of 1 mm. The averaged mean scalp doses [Gy], V24Gy [%], and V30Gy [%] (1SD) for 6MV-3DCRT, 10MV-3DCRT, HIMRT, 6MV-VMAT, and 10MV-VMAT were [26.6 (1.1), 86.4 (7.3), 13.2 (4.2)], [25.4 (1.0), 77.8 (7.5), 13.2 (4.2)], [23.2 (1.5), 42.8 (19.2), 0.2 (0.5)], [23.6 (1.6), 47.5 (17.9), 1.2 (1.8)], and [22.7 (1.7), 36.4 (17.6), 0.7 (1.1)], respectively. Conclusion: Regarding the dose parameters, HIMRT achieved a lower scalp dose compared with 6MV-VMAT. However, the highest ability to reduce the mean scalp dose was showed in 10MV-VMAT. Advances in knowledge: Scalp-sparing WBRT using HIMRT or VMAT may prevent radiation-induced alopecia in patients with BM.

Introduction The administration of systemic corticosteroids is a key strategy for improving COVID-19 outcomes. However, evidence is lacking on combination therapies of antiviral agents and systemic corticosteroids. The objective of this study was to investigate the efficacy and safety of the combination therapy of favipiravir and methylprednisolone in preventing respiratory failure progression in patients with COVID-19 and non-critical respiratory failure. Methods We conducted a multicenter, open-label, single-arm phase II study. The patients received favipiravir 3600 mg on the first day, followed by 1600 mg for a total of 10–14 days. Methylprednisolone was administered intravenously at 1 mg/ideal body weight (IBW)/day from days 1 to 5, followed by 0.5 mg/IBW/day from days 6 to 10 if clinically indicated. The primary endpoint was the proportion of patients requiring mechanical ventilation (MV) (including noninvasive positive pressure ventilation) or those who met the criteria for tracheal intubation within 14 days of the study treatment initiation (MVCTI-14). Results Sixty-nine patients were enrolled and underwent the study treatment. Of them, the MVCTI-14 proportion was 29.2% (90% confidence interval 20.1–39.9, p = 0.200). The proportion of patients who required MV or who died within 30 days was 26.2%, and 30-day mortality was 4.9%. The most significant risk factor for MVCTI-14 was a smoking history (odds ratio 4.1, 95% confidence interval 1.2–14.2). The most common grade 3–4 treatment-related adverse event was hyperglycemia, which was observed in 21.7%. Conclusion The MVCTI-14 proportion did not reach a favorable level in the clinical trial setting with the threshold of 35%. However, the proportion of MV or death within 30 days was 26.6%, which might be close to the findings (28.1%) of the RECOVERY trial, which showed the efficacy of dexamethasone for patients with COVID-19 and non-critical respiratory failure. Further evaluation of this combination therapy is needed. Clinical Trial Registration Japan Registry of Clinical Trials (jRCT) identifier jRCTs041200025. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00512-9.

The majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity.

The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial.Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%.Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met.The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings.To investigate the association between salivary alpha-amylase as an objective measure of psychological stress response and mild cognitive impairment for the implication of psychological stress in the development of mild cognitive impairment.This cross-sectional study involved 865 participants aged ≥ 65 years. A saliva sample was collected in the morning, and the levels of salivary alpha-amylase were assayed. Mild cognitive impairment was evaluated using the Japanese version of the Montreal Cognitive Assessment; a score26 was indicative of mild cognitive impairment. A multivariable logistic regression model was used to examine the association of salivary alpha-amylase and mild cognitive impairment after adjusting for age, sex, current drinking status, current smoking status, body mass index, hypertension, diabetes mellitus, physical activity, education, social support, social network, and heart rate variability.Salivary alpha-amylase was associated with mild cognitive impairment (the multivariable-adjusted odds ratio [95% confidence interval] for the 1-standard deviation increment of log-transformed salivary alpha-amylase was 1.24 [1.07-1.44]). This significant association persisted after adjusting for various confounding factors.Elevation of salivary alpha-amylase was associated with mild cognitive impairment among Japanese community-dwelling older adults. This suggests that salivary alpha-amylase is a useful objective marker of psychological stress responses associated with mild cognitive impairment.

Main text This is the final report of CCT-K7.2021 key comparison of water-triple-point (TPW) cells. The primary objective of CCT-K7.2021 was a comparison of the participant national realizations of the TPW temperature. Each participant laboratory selected one of its TPW cells for use as a transfer cell, directly compared it against its national reference and delivered it to the pilot (NRC). The pilot then compared all transfer cells against two NRC reference cells and, finally, each participant laboratory retrieved its transfer cell and directly re-compared it against its TPW national reference. The initial measurements at the participant laboratories were started in April 2021. The final measurements at the participants' laboratories were completed in September 2022. The final report was approved by the CCT WG-KC in April 2023. The adaptive weighted average procedure was adopted to compute the Key Comparison Reference Value (KCRV) and the degrees of equivalence (DoEs) were reported for the participant laboratories. The maximum difference between two transfer cells was 92 μK with a standard deviation of 26 µK (almost a factor of two improvement compared to CCT-K7 results (2002-2004). The maximum difference between two TPW national realizations was 111 µK, with a standard deviation of 28 µK (improvement similar to the one reported for the transfer cells). While the pooled distribution of CCT-K7 results was bimodal, indicating the presence of two different sub-populations (the population of laboratories that referred to ocean water definition and the population of laboratories that did not consider it), the pooled distribution of CCT-K7.2021 results was no longer bimodal, but slightly asymmetrical, indicating a more harmonized approach to water isotopic corrections. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/. The final report has been peer-reviewed and approved for publication by the CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

The measurements of the difference between the thermodynamic temperature T and the temperature T90 based on the International Temperature Scale of 1990 (ITS-90), (T-T90), by using an acoustic gas thermometer (AGT) working on neon gas is reported in this paper. The AGT introduced a one-liter quasi-spherical resonator made of oxygen-free-copper. The thermodynamic temperature was determined relatively from the speed of sound measurements at a desired temperature regarding to those at the triple point of water. At the present stage, the aimed temperature range was the gallium melting point. Based on the obtained measured speed of sound, the thermodynamic temperature T and the values of (T-T90) were determined, and the associated uncertainties were estimated. The (T-T90) obtained in the present work was found to agree within the estimated uncertainty with the currently reported values that exist in temperature range overlapping with the present work.

The prognostic value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) taken immediately after completion of radiotherapy in lung cancer patients is not well known. The purpose of this study is to assess the prognostic value of PET/CT taken immediately after completion of radiotherapy in lung cancer patients.Patients with primary lung cancer planned to undergo concurrent chemoradiotherapy were enrolled. Patients underwent PET/CT scans at 3 time points: before radiotherapy, within 24hours of completing radiotherapy (im-PET/CT), and 2-9 months after radiotherapy (post-PET/CT). Maximum standardized uptake value (SUVNineteen patients were enrolled. im-PET/CT-SUVPET/CT-SUV

The Breast Cancer Group of the Japanese Radiation Oncology Study Group conducted a nationwide questionnaire survey on the clinical practice of postoperative radiotherapy for breast-conserving treatment for breast cancer. This questionnaire consisted of 18 questions pertaining to the annual number of treated patients, planning method, contouring structure, field design, dose-fractionated regimen, application of hypofractionated radiotherapy, boost irradiation, radiotherapy for synchronously bilateral breast cancer, and accelerated partial breast irradiation. The web-based questionnaire had responses from 293 Japanese hospitals. The results indicated the following: treatment planning is performed using relatively similar field designs and delivery methods; the field-in-field technique is used at more than one-third of institutes; the commonest criteria for boost irradiation is based on the surgical margin width (≤5 mm) and the second commonest criteria was age (≤40 or ≤50 years), although some facilities applied a different age criterion (>70 years) for omitting a tumor bed boost; for conventional fractionation, almost all institutes delivered 50 Gy in 25 fractions to the conserved whole breast and 10 Gy in 5 fractions to the tumor bed. This survey revealed that 43% of hospitals offered hypofractionated radiotherapy, and the most common regimens were 42.56 Gy in 16 fractions for whole-breast irradiation and 10.64 Gy in 4 fractions for boost irradiation. Almost all of the facilities irradiated both breasts simultaneously for synchronously bilateral breast cancer, and accelerated partial breast irradiation was rarely offered in Japan. This survey provided an overview of the current clinical practice of radiotherapy for breast-conserving treatment of breast cancer in Japan.

Objective The majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity. Methods From the Asian international multi-institutional retrospective study involving 13 Japanese, one Thailand, and one Korean institutions based on 469 patients, squamous cell carcinoma (Scc), tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time (TTT) Results Among 469 patients, 162 patients (34.5%) met the criteria of low-risk group, and 63, 41, 43, and 15 patients were categorized in CTVHR D90 50–60 Gy, 60–70 Gy, 70–80 Gy, and >80 Gy, respectively. While 4-y progression-free survival ranged from 66 to 80%, 4-y local control was consistently over 90% in every dose group. Rectum and bladder D2cc and incidence of late adverse events decreased as CTVHR D90 decreased. Conclusions The low-risk patients achieved favorable local control with CTVHR D90

BACKGROUND Real-world data (RWD) and real-world evidence (RWE) are playing increasingly important roles in clinical research and health care decision-making. To leverage RWD and generate reliable RWE, data should be well defined and structured in a way that is semantically interoperable and consistent across stakeholders. The adoption of data standards is one of the cornerstones supporting high-quality evidence for the development of clinical medicine and therapeutics. Clinical Data Interchange Standards Consortium (CDISC) data standards are mature, globally recognized, and heavily used by the pharmaceutical industry for regulatory submissions. The CDISC RWD Connect Initiative aims to better understand the barriers to implementing CDISC standards for RWD and to identify the tools and guidance needed to more easily implement them. OBJECTIVE The aim of this study is to understand the barriers to implementing CDISC standards for RWD and to identify the tools and guidance that may be needed to implement CDISC standards more easily for this purpose. METHODS We conducted a qualitative Delphi survey involving an expert advisory board with multiple key stakeholders, with 3 rounds of input and review. RESULTS Overall, 66 experts participated in round 1, 56 in round 2, and 49 in round 3 of the Delphi survey. Their inputs were collected and analyzed, culminating in group statements. It was widely agreed that the standardization of RWD is highly necessary, and the primary focus should be on its ability to improve data sharing and the quality of RWE. The priorities for RWD standardization included electronic health records, such as data shared using Health Level 7 Fast Health care Interoperability Resources (FHIR), and the data stemming from observational studies. With different standardization efforts already underway in these areas, a gap analysis should be performed to identify the areas where synergies and efficiencies are possible and then collaborate with stakeholders to create or extend existing mappings between CDISC and other standards, controlled terminologies, and models to represent data originating across different sources. CONCLUSIONS There are many ongoing data standardization efforts around human health data–related activities, each with different definitions, levels of granularity, and purpose. Among these, CDISC has been successful in standardizing clinical trial-based data for regulation worldwide. However, the complexity of the CDISC standards and the fact that they were developed for different purposes, combined with the lack of awareness and incentives to use a new standard and insufficient training and implementation support, are significant barriers to setting up the use of CDISC standards for RWD. The collection and dissemination of use cases, development of tools and support systems for the RWD community, and collaboration with other standards development organizations are potential steps forward. Using CDISC will help link clinical trial data and RWD and promote innovation in health data science.

There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 μg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 μg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.

The purpose of the present study was to analyze the feasibility and safety of radiosensitization using hydrogen peroxide for cervical cancer. In superficial tumors, breast cancer and hepatocellular carcinoma, the safety and effectiveness of radiosensitization has been reported; to the best of our knowledge, however, there are no reports on cervical cancer. A total of 20 patients with cervical cancer were recruited. Inclusion criteria were as follows: Patients who required radical external beam radiotherapy (RT); ineligible for or refused brachytherapy; age, ≥20 years; no hematogenous metastasis; Eastern Cooperative Oncology Group Performance Status up to 2; and had not undergone prior treatment. Hydrogen peroxide was used twice a week in combination with RT. A 3% hydrogen peroxide solution-soaked gauze was inserted into the vagina during RT. A total of 45 Gy was delivered in 25 fractions to the whole pelvis with a boost of 10 Gy in 5 fractions if pelvic or para-aortic metastatic lymph nodes were observed. Ultimately, 18 patients were evaluated. Among the 17 patients (excluding one patient with tumor in situ), the one- and two-year overall survival rates were both 90% in patients with stage I/II and 86% in stage III/IV cervical cancer. The adverse events were well tolerated with no severe acute or late adverse events. Although limited by small sample size, short observation time and low radiation dose, the present study demonstrated that radiosensitization treatment may be an option for patients who cannot undergo brachytherapy. The study was retrospectively registered at the university hospital medical information network center (no. UMIN000039045) on January 6, 2020.

A new acoustic gas thermometry (AGT) system, which introduces a 1-L quasi-spherical resonator (QSR) made of oxygen-free copper, was built at the National Metrology Institute of Japan (NMIJ/AIST). The inner surface of the new QSR was machined using a diamond-turn tool. Improvement in the pressure measurement was introduced to allow direct measurement of the gas pressure in the resonator. The new AGT system was evaluated based on the measurement of the speed of sound in argon at the triple point of water and the melting point of gallium under the pressure range from 700 kPa down to 50 kPa. Based on these speed of sound measurements, the thermodynamic temperatures at the melting point of gallium were determined. The speed of sound measurements at isotherms of 283.15 K and 293.15 K were also conducted, and the related thermodynamic temperatures were determined. Based on the measured thermodynamic temperature T, the values of difference between T and the temperature T90 based on the International Temperature Scale of 1990 (ITS-90), (T − T90), along with the associated uncertainties, were calculated. The (T − T90) obtained in the present work were 1.3 ± 0.7 mK, 2.7 ± 0.8 mK, and 4.1 ± 0.8 mK for T90 of 283.15 K, 293.15 K, and 302.9146 K, respectively. These values were found to be in agreement within the estimated uncertainty with the currently reported values that exist in temperature range overlapping with the present work.

High-temperature standard platinum resistance thermometers (HTSPRTs) are used to establish the International Temperature Scale of 1990 (ITS-90) for temperatures up to 960 °C. Currently available thermometers, which may differ in the design of the platinum winding of the sensor, the shape and finish of the sensor frame, the frame material, the protective sheaths, and sealing materials, need some treatments to exhibit the stabilities expected of them and some of the causes of the instability are not well understood. This paper demonstrates a novel model of commercial HTSPRT that reportedly employs a novel sensor winding construction designed to eliminate instability arising from strain on the sensor winding due to differential thermal expansion between the sensor and the sensor frame. The stability of eight different HTSPRTs, including the novel model, are compared at the triple point of water (TPW), the melting point of gallium, and the freezing points of tin, zinc, aluminum and silver. Heat treatments included annealing at 500 °C, a preheating temperature for use at the freezing points of aluminum and silver, and at 800 °C, which was selected for checking the stability of the HTSPRTs in the middle of the temperature range between the freezing points of aluminum and silver. The consistency of the resistance values at the different fixed points was also confirmed by calculating the S parameter. We found three HTSPRTs stable during the described thermal conditions within ± 0.5 mK at the TPW. The novel model of commercial HTSPRT was the best one with a stability in the resistance at the TPW of within ± 0.3 mK over the entire temperature range. These indicate that the stable three HTSPRTs are promising instruments to provide accurate temperature scale at temperatures from the freezing point of aluminum up to the freezing point of silver based on the ITS-90.

Submitting data compliant with the Clinical Data Interchange Standards Consortium (CDISC) standards is mandatory for new drug applications (NDAs). The standards set by CDISC are widely adopted in the pharmaceutical business world. Introduction of CDISC standards in academia can be necessary to reduce labor, resolve the shortage of data managers in academia, and gain new knowledge through standardized data accumulation. However, the introduction of CDISC standards has not progressed in communities within the academia that do not apply for NDAs. Therefore, herein, we created study data tabulation model (SDTM)-compliant datasets within the academia, without outsourcing, to reduce costs associated with investigator-initiated clinical trials. First, we input data from paper case report forms (CRFs) into an electronic data capture system with minimal function for paper CRFs, "Ptosh," which is compatible with SDTM. Then, we developed a generic program to convert data exported from Ptosh into fully SDTM-compliant datasets. The consistency was then verified with an SDTM validator, Pinnacle21 Community V3.0.1 (P21C). This resulted in generation of SDTM datasets, resolving all "Rejects" in P21C, thereby achieving the required quality level. Although Ptosh directly exports data in SDTM format, manual mapping of items on CRFs to SDTM variables prepared in Ptosh is necessary. SDTM mapping requires extensive knowledge and skills, and it was assumed that mapping is challenging for the staff without in-depth knowledge of CDISC standards and datasets. Therefore, for CDISC dissemination in academia, it is crucial to secure the staff, time, and funding to acquire the knowledge.

We have designed and evaluated a simple and practical system for CD3+ (T-lymphocyte) and CD19+ (B-lymphocyte) cell counting on-chip using a PDMS microfluidic chip which captures these cells using a pillarbased filtration technique. Conventional pillar-based or membrane-based cell separation methods suffer from the problem of cell clogging, thereby reducing the separating and capturing efficiency of the device. To address these issues, we proposed a unique and simple design of a microfluidic chip with an escape route at the pillar-based cell filtration area in the chip which prevents cell clogging. Currently, the diagnosis, monitoring and treatment of immunodeficiency disorder require quantifying the leukocyte population, especially T-lymphocytes and Blymphocytes, in whole blood. We evaluated the performance of our microfluidic chip by obtaining the ratio of T-lymphocytes and Blymphocytes from whole blood and compared the results to those obtained using a flow cytometer. We confirmed that the cell capture area of the microfluidic chip remains clog-free. We achieved 99.8% efficiency in capturing leukocytes using the microfluidic chip, and the ratio of CD3+ and CD19+ had a coefficient of r = 0.9876 and a coefficient of variation (CV) of 2.77%, from 1 μL of whole blood sample.

Providing an accurate count of total leukocytes and specific subsets (such as T-cells and B-cells) within small amounts of whole blood is a rather challenging ordeal due to the lack of techniques that enable the separation of leukocytes from a limited amount of whole blood. In a previous study we designed a microfluidic chip utilizing a micropillar array to isolate T-cells and B-cells from the sub-microliter of whole blood. Due to the variability of cells in size, morphology and color intensity, a Histogram of Oriented Gradients (HOG) based Support Vector Machine (SVM) classifier was proposed with an average accuracy of 94%, specificity of 99% and sensitivity of 90%. The HOG can separate the cells from the background with a high accuracy rate however, some noise is similar in shape and size to the actual cells and this results in misclassification. To alleviate this situation, in this study a convolutional neural network is trained and used to distinguish T-cells and B-cells with an accuracy rate of 98%, a specificity of 99% and a sensitivity of 97%. We also propose an HOG feature based SVM classifier to preselect the detection windows to accelerate the detection to process images in less than 10 min. The proposed on-chip cell detecting and counting method will be useful for numerous applications in diagnosis and for monitoring diseases.

Summary Background & aims The associations between dietary magnesium intake and stroke and coronary heart disease (CHD) incidences are inconsistent and not established in Asian. We aimed to determine the association between dietary magnesium intake and the risk of stroke and CHD in a Japanese population. Subjects/Methods We studied 85,293 Japanese subjects by questionnaire at baseline (age 45–74 years, without cardiovascular disease or cancer in 1995 and 1998 for Cohorts I and II, respectively). The participants were followed until the end of 2009 and 2010 in Cohorts I and II, respectively. Dietary magnesium intake was estimated from a self-administered 138-item food-frequency questionnaire. Results After 1,305,738 person-years of follow-up, 4110 strokes and 1283 cases of CHD were documented. The multivariable-adjusted hazard ratios (HRs, 95% confidence intervals, 95%CIs) of CHD for the fourth and fifth quintiles of dietary magnesium intake were 0.70 (0.50–0.99) and 0.66 (0.44–0.97) in men (P for trend = 0.036), respectively, and third quintile of dietary magnesium intake was 0.61 (0.39–0.96) in women (P for trend = 0.241), compared with the lowest quintile in men and women. We observed no decreased risks of incident stroke in men or women with higher dietary magnesium intakes. Conclusions Higher dietary magnesium intake was associated with a reduced risk of CHD in Japanese men.

Absolute counting of total leukocytes and specific subset (such as T-cells and B-cells) within small amounts of whole blood is difficult due to the lack of techniques that enables separation of leukocytes from limited volume of whole blood. In this study, a microfluidic chip equipped with a size controlled micropillar array for highly separation of T-cells and B-cells from sub-microliter of whole blood was studied. Based on the difference in size and deformability, leukocytes were separated from other blood cells by micropillar arrays. However, the variability of cells in size, morphology and color intensity along with the spectrum crosstalk between fluorescence dyes make cell detection among pillars extremely difficult. In this paper, an support vector machine supervised machine learning classifier based on both Histogram of Oriented Gradients (HOG) and color distribution features was proposed to distinguish T-cells and B-cells fast and robustly. HOG features were utilized to detect cells from background and noise; color distribution features were employed to alleviate the effect of fluorescence spectrum crosstalk. Experiment showed we achieved average detection accuracy of 94% for detecting T-cells and B-cells from the background. Furthermore, we also got 96% accuracy with cross validation to detect T-cells from B-cells. Both theoretical analysis and experiments demonstrated the proposed method and system has high performance in T-cells and B-cells counting. And our microfluidic cell counting system has great potential as a tool for point-of-care leukocyte analysis system.

PURPOSE/OBJECTIVE(S) Uterine cancer patients with supraclavicular or mediastinal lymph node metastasis are usually considered candidates for systemic chemotherapy or are treated with palliative radiotherapy for specific symptom control. However, if there are no additional hematogenous metastasis, we hypnotized that curative radiotherapy could be effective. The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy with curative intent to this type of patients. MATERIALS/METHODS The medical records of uterine cancer patients with supraclavicular or mediastinal lymph nodal metastases, who received radiotherapy for curative intend were reviewed. Both who were initial presented with these lymph node metastases and who were presented as recurrence after treatment were included. Patients with hematogenous metastasis were excluded from the analysis. Overall survival and progression free survival, acute and late adverse effect (NCI-CTC ver. 5) was evaluated. In patients with recurrence, the first site of recurrence was also recorded. RESULTS Eligible patients were 30 (supraclavicular lymph node metastasis: 23, mediastinal lymph node metastasis: 7). Median age was 52 (range 36-82) years. The primary site was cervical cancer in 24 and endometrial cancer in six. De novo tumors were 20 and recurrent tumors were 10. Out of the cervical cancer patients, one patient presented with adenocarcinoma, and the rest had squamous cell carcinoma. Concomitant systemic therapy was performed in 26 patients, which was platinum based in 20 patients, 5FU in five patients, medroxyprogesterone in one patient. The patients with PS0, 1, 2 were 27, 2, 1, respectively. All patients received 60 Gy in 30 fractions to the metastatic site (if de novo tumors, also brachytherapy, whole pelvis and paraaortic lymph node was included). Median follow-up was 16 (range 3-120) months. Acute grade 3-4 esophagitis, neutropenia, anemia, and thrombocytopenia were observed in 6.7%, 56.7%. 40.0% and 13,3%. Late toxicity was observed in one patient which was grade 1 skin induration. One- and two-year overall survival was 66.1% and 45.4%, respectively. One-and two-year progression free survival was 47.4% and 30.7%, respectively. On multivariate analysis, serum squamous cell carcinoma antigen < 6 ng/mL had correlation with good progression free survival. First site of recurrence was lymph node in 11, lung metastasis in six patients, brain metastasis in three patients, and peritoneal dissemination in two patients (one patients presented with two sites of metastasis). CONCLUSION Curative radiotherapy is feasible for Stage IVB or recurrent uterine cancer presenting with supraclavicular or mediastinal lymph node metastasis without hematogenous metastasis. Large scale, prospective trials are warranted. AUTHOR DISCLOSURE A.I. Saito: None.

Effects of resistance training are well known to be specific to tasks that are involved during training. However, it remains unclear whether neuromuscular adaptations are induced after adjacent joint training. This study examined the effects of hip flexion training on maximal and explosive knee extension strength and neuromuscular performance of the rectus femoris (RF, hip flexor, and knee extensor) compared with the effects of knee extension training. Thirty-seven untrained young men were randomly assigned to hip flexion training, knee extension training, or a control group. Participants in the training groups completed 4 weeks of isometric hip flexion or knee extension training. Standardized differences in the mean change between the training groups and control group were interpreted as an effect size, and the substantial effect was assumed to be ≥0.20 of the between-participant standard deviation at baseline. Both types of training resulted in substantial increases in maximal (hip flexion training group: 6.2% ± 10.1%, effect size = 0.25; knee extension training group: 20.8% ± 9.9%, effect size = 1.11) and explosive isometric knee extension torques and muscle thickness of the RF in the proximal and distal regions. Improvements in strength were accompanied by substantial enhancements in voluntary activation, which was determined using the twitch interpolation technique and RF activation. Differences in training effects on explosive torques and neural variables between the two training groups were trivial. Our findings indicate that hip flexion training results in substantial neuromuscular adaptations during knee extensions similar to those induced by knee extension training.

Background Despite recent progress in blood systems, transfusion errors can occur at any time from the moment of collection through to the transfusion of blood and blood products. This study investigated the actual statuses of blood transfusion errors at institutions of all sizes in Aichi prefecture. Materials and methods We investigated 104 institutions that perform 98 % of the blood transfusions in Aichi prefecture, and investigated the errors (incidents/accidents) that occurred at these facilities over 6 months (April to September, 2017). Incident/accident data were collected from responses to questionnaires sent to each institution; these were classified according to the categories and risk levels. Results Ninety-seven of the 104 institutions (93.3 %) responded to the questionnaire; a total of 688 incidents/accidents were reported. Most (682 cases; 99.2 %), were classified as risk level 2; however, 6 were level 3 and over, which included problems with autologous transfusion and inventory control. Approximately one-half of the incidents/accidents (394 cases; 57.3 %), were related to verification and the actual administration of blood products at the bedside; more than half of these incidents/accidents occurred at large-volume institutions. Meanwhile, a high frequency of incidents/accidents related to transfusion examination and labeling of blood products was observed at small- or medium-sized institutions. The reasons for most of these errors were simple mistakes and carelessness by the medical staff. Conclusions Our results emphasize the importance of education, operational training, and compliance instruction for all members of the medical staff despite advances in electronic devices meant to streamline transfusion procedures.

We have developed an adiabatic calorimeter with a small glass Hg cell to calibrate capsule-type standard resistance thermometers (SPRTs) at the triple point of Hg (TPHg), which is one of the defining fixed point of the International Temperature Scale of 1990 (ITS-90). Using this system with high-purity Hg (99.999 99 %), we calibrated SPRTs at the TPHg and evaluated the uncertainty of the calibration. Compared with a calibration system at the National Metrology Institute of Japan (NMIJ/AIST), which uses a large stainless steel Hg cell, for a small cell in an adiabatic calorimeter the temperature distribution from hydrostatic pressure can be suppressed. In addition, the influence of heat flux can also suppressed by using the adiabatic calorimeter. Consequently, the standard combined uncertainty for the realization of TPHg was estimated to be 0.12 mK, much less than the uncertainty of the conventional system using the large stainless Hg cells. Furthermore, by measuring the cooling curve of Hg at different cooling rates, we confirmed that the degree of supercooling of high-purity Hg in the small glass cell reached approximately 18 K, which is much larger than that achievable in not only large Hg cells but also small cells. This large supercooling may be related to the high purity of the Hg employed, the small hydrostatic height of the Hg, and/or the surface contact between Hg and cell.