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With the growth of the EV/HV market, the main cause of cabin noise has changed from engine driving sound to air conditioner noise. The blower noise is the largest in the air conditioner noise, and the noise reduction is urgent. Separated and reattached flows between fan blades are considered to be the main sources of blower noise. In the past, we tried to reduce the noise by reducing the separation. This time, the blade shape to further reduce the separation was produced and evaluated. As a result, the noise was greatly reduced, but a new problem was found that there was a flow velocity condition in which the noise increased despite the small separation. Therefore, we visualized the flow between blades by PIV, investigated the state of separated and reattached flow in detail, and investigated the factors related to noise increase and decrease by measuring noise and pressure fluctuation of blade surface simultaneously. As a result, it was found that the noise generation condition in the separation reattachment flow between blades is not only the size of separation but also the distance of separation shear layer from blade surface and the strength of vortex generated in shear layer.

Magmatic fluids within the crust may exist under supercritical conditions (e.g. >374°C and >22.1 MPa for pure water). Geothermal systems using such supercritical fluids have gained attent...

Purpose In patients with epidermal growth factor receptor (EGFR)-mutated, advanced, non-small cell lung cancer (NSCLC), common gefitinib-sensitive EGFR mutations that predict a greater response to therapy include the exon 19 deletion and L858R point mutation. The objective of this study was to evaluate whether body surface area (BSA), body weight (BW), and body mass index (BMI) affect gefitinib efficacy in such patients. Methods The medical charts of 138 consecutive patients with advanced NSCLC harboring sensitive EGFR mutations, who underwent gefitinib treatment, were reviewed. The median BSA and BW were used as cutoff values to evaluate their impact on gefitinib efficacy. BMI was categorized as underweight (

This study clarifies the hydrothermal system of Jigokudani Valley near Mt. Tateyama volcano in Japan by using a combination of audio-frequency magnetotelluric (AMT) survey and hot-spring water analysis in order to assess the potential of future phreatic eruptions in the area. Repeated phreatic eruptions in the area about 40,000 years ago produced the current valley morphology, which is now an active solfatara field dotted with hot springs and fumaroles indicative of a well-developed hydrothermal system. The three-dimensional (3D) resistivity structure of the hydrothermal system was modeled by using the results of an AMT survey conducted at 25 locations across the valley in 2013–2014. The model suggests the presence of a near-surface highly conductive layer of 2 O isotopic ratios. All hot-spring waters had low pH and could be categorized into three types on the basis of the Cl − /SO 4 2 − concentration ratio, with all falling largely on a mixing line between magmatic fluids and local meteoric water (LMW). The geochemical analysis suggests that the hydrothermal system includes a two-phase zone of vapor–liquid. A comparison of the resistivity structure and the geochemically inferred structure suggests that a hydrothermal reservoir is present at a depth of approximately 500 m, from which hot-spring water differentiates into the three observed types. The two-phase zone appears to be located immediately beneath the cap rock structure. These findings suggest that the hydrothermal system of Jigokudani Valley exhibits a number of factors that could trigger a future phreatic eruption.

Meningitis retention syndrome (MRS), a rare complication of aseptic meningitis, can present with acute urinary retention. The rupture of a dermoid cyst, which is a benign intracranial tumor, can sometimes induce chemical meningitis. We herein present a case of chemical meningitis and acute urinary retention that was induced by the rupture of a dermoid cyst. The patient experienced urinary retention for approximately 60 days, and then made a complete recovery thereafter. This is the first reported case of acute urinary retention due to the rupture of a dermoid cyst.

The Kusatsu-Shirane volcano is a Quaternary andesitic-to-dacitic active volcano located on the central Honshu Arc. The volcano is known to have had repeated phreatic eruptions in last 200 years. A number of geochemical and geophysical studies have been conducted around the Yugama crater lake, the focus of current volcanic activity. However, the 2018 unexpected phreatic eruption occurred at Mt. Motoshirane, a different pyroclastic cone from that which hosts Yugama. There were also frequent magmatic eruptions until 1500 years ago at this cone and the magma produced at that time has not yet cooled and solidified. A better understanding of the magmatic hydrothermal system of this volcano requires structural information gathered over a larger area, and to greater depths, than has been achieved to date. Here, we describe the three-dimensional (3-D) electrical resistivity structure around Mt. Motoshirane down to a depth of ~10 km using broadband magnetotelluric (MT) data (320–0.0005 Hz) collected in 2015 and 2016. The 3-D resistivity structure model shows an extensive low-resistivity layer at depths of 1–3.5 km beneath the summit. However, structures characteristic of the presence of magma are not observed beneath this layer. It could be too deep or too small to be detected. Combining the new data with results of previous geochemical and geophysical studies, we interpret the conductor as a hydrothermal fluid reservoir that supplies fluids to the crater lake and to hot springs on the eastern and western flanks of the volcano. The existence of a fluid reservoir that extends from the vicinity of the Yugama crater lake to the subsurface beneath an inactive pyroclastic cone that has produced repeated magmatic eruptions in the past suggests that a large-scale magmatic hydrothermal system is developing beneath the volcano.

The efficacy of gefitinib [an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor] in elderly patients with non-small cell lung cancer (NSCLC) and EGFR mutation has not been elucidated. Therefore, the objective of this study was to investigate the efficacy and feasibility of gefitinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations. We retrospectively evaluated the clinical effects of gefitinib as a first-line treatment for elderly (≥75 years) NSCLC patients with EGFR mutations (exon 19 deletion or exon 21 L858R mutation). All patients were initially treated with gefitinib (250 mg/day) at seven institutions. Between January 2006 and December 2012, 62 patients (17 men, 45 women) with a median age of 80 years (range, 75–89 years) were included in our analysis. The overall response and disease control rates were 61.2 and 83.8 %, respectively, and the median progression-free survival and overall survival were 13.2 and 19.0 months, respectively. Common adverse events included rash, diarrhea, and liver dysfunction. Major grade 3 or 4 toxicities included skin rash (3.2 %) and increased levels of aspartate aminotransferase or alanine aminotransferase (21.0 %). Gefitinib treatment was discontinued owing to adverse events of liver dysfunction in 3 patients, drug-induced pneumonitis in 2, and diarrhea in 1. First-line gefitinib could be a preferable standard treatment in elderly patients with advanced NSCLC harboring sensitive EGFR mutations.

Familial Mediterranean fever (FMF) can be classified into typical and incomplete/atypical types. Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome-like symptoms have been found in atypical type carrying P369S-R408Q mutations in the responsible gene MEFV. A 28-year-old female with recurrent fever and her young sisters and mother, all of whom had tonsillectomy for tonsillitis, carried heterozygous alterations involving E148Q/P369S/R408Q. A diagnosis of atypical FMF, MEFV exon3 variants with PFAPA syndrome-like symptoms, was made.

Breast cancer/Anxiety/Chromogranin A/State-Trait Anxiety Inventory (STAI)/Radiation. We conducted a prospective study to assess the a nxiety and salivary Chromogranin A (CgA), which is considered to be a biomarker of the stress response, in outpatients receiving breast conserving surgery followed by radiation therapy (RT) to the whole breast. Fifty consecutive patients who received wholebreast RT were enrolled in this study. The anxiety levels were measured by the State-Trait Anxiety Inventory (STAI) at the beginning of RT (baseline), 30 Gy, completion of RT, and 1 and 3 months after RT. Salivary CgA levels were also measured at the same time. The mean state anxiety score for all patients was 46.16 with a standard error (SE) of 1.57 at the beginning of RT (baseline) which continued to decline during and after RT. It reached its lowest score with 36.34 ± 1.56 at 3 months after RT (p < 0.0001). The mean trait anxiety score for all patients was 43.10 ± 1.54 at baseline and remained constant during RT but began to decline after completion of RT and reached a low level at 3 months after RT (p = 0.0021). The mean salivary CgA concentration for all patients demonstrated no consistent trends over time, but at 30 Gy the concentration showed a significant decreasing pattern (p = 0.0473). Salivary CgA concentrations and state anxiety and trait anxiety scores at all time points showed no correlation. The mean anxiety scores measured by STAI showed no positive correlation with s alivary CgA concentration for breast cancer patients undergoing radiation therapy following breast conserving surgery.

Idiopathic pulmonary fibrosis is a destructive inflammatory disease with unknown etiology and limited therapeutic options. Inflammation and damage due to deregulated cytokine expression are definitely involved. 17(R)-ResolvinD1(RvD1) has potent anti-inflammatory pro-resolving activity. Recently, the specific receptors that bind RvD1 were identified on human macrophages. Monocyte chemotactic and activating factor (MCP-1) is one of the key chemokine by regulating migration of inflammatory cells. It is produced by macrophages and plays an integral role in the development of some pulmonary diseases. We examined the effect of 17(R)-RvD1 by assessment of MCP-1 and any other cytokines mRNA. We used 8-10-weeks old female C57BL/6J mice and administerd BLM subcutaneouly via micro-osmotic pump. 17(R)-RvD1 was injected intraperitoneally for 5 days consecutively from day1. We measured cell differentiation and total number in bronchoaveloar fluid(BALF) and sacrificed mice at day7, 14 and 28. At day 7, MCP-1 mRNA was significantly lower in BLM/RvD1 group than BLM/Vehicle(veh) group. However, macrophages in BALF in BLM/RvD1 group resulted in no statistical difference compared with BLM/veh group. At day 14, the level of TGF- b1 mRNA after 17(R)-RvD1 treatment were decreased. The significant decreases of macrophages were observed in BALF from BLM/RvD1 group vs. from BLM/veh group. At day 28, the histology of the lung sections in the BLM/RvD1 group exhibited less collagen deposition. These results suggest that 17(R)-RvD1 ameliorates pulmonary fibrosis partly through the reduction of MCP-1 production during onset of the acute inflammatory phase leading to attenuate infiltration of inflammatory cells.

Purpose: The aims of this study were twofold: ( 1 ) to examine the effects of dual inhibition of 2 members of the HER family, the epidermoid growth factor receptor (EGFR) and HER2/ neu , by gefitinib (ZD1839) and trastuzumab on radiosensitivity; and ( 2 ) to explore the molecular mechanism of radiosensitization especially focusing on the survival signal transduction pathways by using A431 human vulvar squamous carcinoma cells expressing EGFR and HER2/ neu . Methods and Materials: The effects of inhibitors on the radiation-induced activation of EGFR and/or HER2/ neu , and the intracellular proteins that are involved in their downstream signaling, were quantified by the Western blot. Radiosensitizing effects by the blockage of EGFR and/or HER2/ neu were determined by a clonogenic assay. Results: Radiation-induced activation of the EGFR and HER2/ neu was inhibited with ZD1839 and/or trastuzumab. ZD1839 also inhibited the radiation-induced phosphorylation of HER2/ neu . Radiation in combination with the HER family inhibitors inhibited the activation of Akt and MEK1/2, the downstream survival signaling of the HER family. ZD1839 enhanced radiosensitivity with a dose-modifying factor (DMF) (SF3) of 1.45 and trastuzumab did so with a DMF (SF3) of 1.11. Simultaneous blockade of EGFR and HER2/ neu induced a synergistic radiosensitizing effect with a DMF (SF3) of 2.29. Conclusions: The present data suggest that a dual EGFR and HER2/ neu targeting may have potential for radiosensitization in tumors in which both of these pathways are active.

Previously, we conducted a nationwide survey of primary central nervous system lymphoma (PCNSL) treated between 1985 and 1994 in Japan. In the present study, we conducted further investigations of PCNSL patients treated between 1995 and 1999 to clarify possible changes with time in the clinical features, treatment, and outcome of this disease. Thirteen Japanese institutions were surveyed, and data on 101 patients with histologically-confirmed PCNSL were collected. These data were compared with those of 167 patients treated at the same institutions between 1985 and 1994. Regarding patient and tumor characteristics, the proportion of patients with good performance status (PS) was significantly higher in the group treated during 1995–1999 than in that treated during 1985–1994, but other characteristics were not significantly different. Regarding treatment, more patients in the more recent period (66%) received systemic chemotherapy than those in the preceding period (53%, P = 0.049). For all patients, including those who did not complete radiotherapy, the median survival time was 17 months and 30 months in patients treated between 1985 and 1994 and those treated between 1995 and 1999, respectively, and the 5-year survival rate was 15% versus 31% (P = 0.0003). In both patient groups, higher age and tumor multiplicity were associated with poor prognosis in multivariate analysis. In patients treated between 1995 and 1999, those who received systemic chemotherapy showed significantly better prognosis than those who did not (P = 0.0049), but the difference was not significant in multivariate analysis (P = 0.23). The high survival rates observed in the present survey are comparable with those of recent prospective studies employing intensive chemoradiotherapy. The improvement in prognosis appeared to result, at least in part, from the increase in the proportion of patients with better PS. Since the clinical feature and treatment outcome of patients with PCNSL can thus change with the era, historical control data should not be used in comparing different treatment modalities.

A 24-year-old woman was admitted to our department for further examination of hypercalcemia, a high level of intact parathyroid hormone (PTH) and a right parathyroid tumor. She complained of bone pain throughout her body and was unable to walk due to systemic cystic osteofibrosis, including a brown tumor of the left lower extremities. Neck ultrasonography (US) and magnetic resonance imaging (MRI) revealed a tumor 2 cm in diameter in the upper side of the right thyroid lobe. 99mTc sestamibi (99mTc-MIBI) imaging and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) were performed to diagnose primary hyperparathyroidism and examination of other parathyroid glands. However, neither imaging modality detected the parathyroid tumor. To confirm the diagnosis, we performed selective venous sampling around the parathyroid and the patient was diagnosed with primary hyperparathyroidism due to a right parathyroid tumor. Resection of the right parathyroid tumor was performed and the pathological diagnosis was parathyroid adenoma. To date, both 99mTc-MIBI and FDG-PET are useful to localize parathyroid tumors. In this case, however, neither modality detected the tumor. Although recent studies state that expression of P-glycoprotein (P-gp) in parathyroid tumors plays an important role in the false-negative results of both 99mTc-MIBI scans and FDG-PET, immunohistological study detected no P-gp expression in the parathyroid tumor in the current case.

Docetaxel has shown remarkable radiosensitizing propertiesin vitro. In this study we investigated whether the addition of docetaxel to radiotherapy enhanced tumor response in patients with advanced or recurrent breast cancer. A total of 35 patients were enrolled in this study. Docetaxel was administered concurrently during radiotherapy. Radiation doses were 54 to 69 Gy (median 60 Gy). In those enrolled through January 2000, docetaxel 40 mg/m2 was administered biweekly (once every two weeks), with subsequent dose adjustments based on tolerance and bone marrow and liver function. Beginning in February 2000, a weekly docetaxel schedule was used instead. This new regimen was based on data suggesting reduced myelosuppression with this regimen. The weekly dose rate was 20 mg/m2, with dose reductions for impaired organ function. All patients were evaluated for toxicity and response and a total of 40 irradiated sites were evaluated for local response. The overall response rate of irradiated sites was 95% and the CR rate was 68%. CR and PR were achieved in 40%, 37% of patients, respectively. Acute toxicities were tolerated by most patients: 17% had Grade 3-4 neutropenia, 6% had Grade 3-4 radiation dermatitis, and 3% had Grade 3-4 pneumonitis. The combination of docetaxel with radiotherapy is an active and safe regimen in patients with inoperable advanced or recurrent breast cancer. We determined the recommended dose of docetaxel with concomitant radiotherpy to be 20 mg/m2 weekly for a Phase II study. Further study is necessary to assess the impact of this treatment on long-term outcome.

Radiotherapy plays an important role in the management of cancer patients, and half of the patients with malignant tumors are treated with radiotherapy in the United States. In Japan, the necessity of radiation therapy has come to be widely acknowledged in cancer treatment, and more and more cancer patients are being treated with radiation. External beam radiation is the most-used radiotherapy at the present time. The advantage is that this treatment modality can be used in a short time, although the problem is that not only the cancer lesion but also the surrounding normal tissue is irradiated,causing an adverse effect on normal tissue. In order to solve this problem,treatments such as 3D-Conformal Radiation Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT), Stereotactic Radiation Surgery (SRS) and Stereotactic Radiation Therapy (SRT) are clinically used as an extremely precise radiotherapy, thanks to the advances in computer technology in recent years. Therefore, the purpose of these extremely precise radiation therapies is to administer a high dose to the tumor intensively, and to suppress quantities of magnetism to normal tissues. IMRT treatment results for prostate cancer patients and head and neck cancer patients are reportedly better than with other irradiation methods. In this chapter,we explain the external irradiation method with the focus on IMRT and the extremely precise radiotherapy preformed in the Tokyo Women's Medical University Hospital.

Radiotherapy is considered to be associated with psychological distress. We assessed the mental status, anxiety, and the factors associated with these in cancer patients about to receive radiotherapy.Hospitalized patients about to receive radiotherapy participated. Psychological status was assessed by a psychiatrist, based on interview about the type of anxiety related to cancer or radiotherapy as well as self-rating questionnaires.Eligible data were collected from 94 patients. The incidence of mental disorders was 20%. The total mood disturbance scores were significantly higher in patients with poor performance status. The most common type of anxiety regarding radiotherapy was acute adverse effect, and the predictors were palliative treatment and living alone.Mental disorders, mood disturbance, and anxiety in patients cannot be neglected in radiation oncology practice. Especially careful attention should be paid to patients with these predictive factors.

The aim of this study was to improve tumor control, the survival rate and organ preservation for locally advanced head and neck cancer by using induction chemotherapy followed by hyperfractionated radiotherapy and concurrent chemotherapy.Thirty-five patients with stage III-IVB head and neck cancer were treated with this protocol. Induction chemotherapy consisted of cisplatin and fluorouracil and concurrent chemotherapy consisted of carboplatin and doxifluridin. Radiotherapy was administered twice a day until a dose of 72 Gy was reached.Twenty-two (63%) and 13 patients (37%) achieved complete responses and partial responses, respectively. In terms of non-hematological toxicities, grade 3 mucositis was observed in 49% of the patients. The overall 5-year survival was 53.5% and the progression-free survival was 40.6%.Response to induction chemotherapy was useful as a predictive factor for ultimate outcome and organ conservation. More intensive regimen or other combination chemotherapy is needed to improve treatment outcome with hyperfractionated radiotherapy.

We report a case of recurrent breast cancer with chronic renal failure in a 58-year-old female. She could be treated on an outpatient basis under good general condition for most of her remaining life by chemoradiotherapy in combination with hemodialysis. Modification of the chemoradiotherapy procedures and collaboration of medical staff including the doctor in charge of home medical care and her family was indispensable in keeping her hospital stay as short as possible.

Tamotsu Ishizuka,1,2 Takeshi Hisada,2 Yosuke Kamide,2 Haruka Aoki,2 Kaori Seki,2 Chisato Honjo,1 Hiroyuki Sakai,1 Maiko Kadowaki,1 Yukihiro Umeda,1 Miwa Morikawa,1 Masaki Anzai,1 Shingo Ameshima,1 Takeshi Ishizaki,1 Kunio Dobashi,2 Masanobu Yamada,2 Motoyasu Kusano3 1Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Japan Background: Losing the sense of smell, which suggests eosinophilic rhinosinusitis, is a subjective symptom, sometimes reported in asthmatic patients taking controller medication. Upper abdominal symptoms, suggesting gastroesophageal reflux disease (GERD) or functional dyspepsia, occur also in these patients. However, the relationship between these symptoms, concomitant with asthma, and the intensity of eosinophilic airway inflammation remains obscure. Objective: To assess the symptoms of asthma and rhinosinusitis, and to examine the relationship between the symptoms and bronchial inflammation, a new questionnaire, the G scale, was developed. To investigate the effects of GERD, dyspepsia, and rhinosinusitis on asthma symptoms and bronchial inflammation, the symptoms of asthma and rhinosinusitis obtained by the G scale, upper abdominal symptoms obtained by the modified F scale, a questionnaire for GERD and dyspepsia, and fractional exhaled nitric oxide (FeNO) were analyzed. Methods: A prospective, observational study was performed in four hospitals in Gunma prefecture, and a retrospective analysis was done using data obtained from five hospitals in Gunma prefecture and Fukui prefecture, Japan. A total of 252 patients diagnosed as having asthma participated in the prospective study. Results: The frequency of daytime phlegm or losing the sense of smell had a positive correlation with FeNO levels in asthmatic patients taking controller medication. Upper abdominal symptoms, as well as symptoms suggesting rhinitis, were well correlated with asthma symptoms. However, neither upper abdominal symptoms nor rhinitis symptoms increased FeNO levels, which reflect eosinophilic airway inflammation during treatment for asthma. On the other hand, the degree of upper abdominal symptoms or dyspepsia symptoms had a weak but significant negative correlation with FeNO levels. Conclusion: Daytime phlegm and losing the sense of smell suggest that eosinophilic airway inflammation persists, despite anti-inflammatory therapy, in patients with asthma. Although rhinitis and GERD made the subjective symptoms of asthma worse, they did not seem to enhance eosinophilic airway inflammation. Keywords: asthma symptoms, FeNO, rhinosinusitis, GERD, dyspepsia&nbsp