Proceedings of the Workshop on Geothermal Reservoir Engineering

A long term interference test was conducted under conditions of multiwell variable flow rate at Takigami for about ten months in 1987. The test data have been analyzed with an on-line analysis method on the basis of the linesource solution. This method employs Kalman filtering to process the data and then provides the best estimates of reservoir transmissivity and storativity when a new pressure data at an observation well becomes available. The pressure changes measured at seven observation wells have been analyzed with the present method using an infinite reservoir model. The data from one observation well have been further analyzed assuming a presence of a linear boundary. Performances of the parameters estimated for different reservoir models are compared. Fairly good estimates of reservoir parameters are obtained on the basis of an infinite reservoir model for two wells using the entire pressure data whereas for other five wells using a part of the pressure data

Biomechanical analysis of load distribution in porcine hip joints at different acetabular coverages

Abstract Background Developmental dysplasia of the hip causes secondary osteoarthritis. Finite element analysis suggests high hip joint contact pressure in patients with hip dysplasia and a reduction in contact pressure after periacetabular osteotomy. However, few biomechanical studies have examined the load distribution in the hip joint. This study aimed to investigate the biomechanical properties of load distribution in porcine hip joints at different acetabular coverages. Methods Six porcine hip joints were analyzed using three models: 1) neutral coverage, 2) 15° under-coverage (defined as dysplasia model), and 3) 15° over-coverage created by varying the acetabular coverage. The load distribution was assessed using a pressure-mapping sensor system after applying a loading force of 100 N to the hip joint. Results In the dysplasia model, the load was concentrated at the acetabular rim; in the neutral and over-coverage models, it was dispersed. The average contact pressure was significantly higher in the dysplasia model than in the neutral coverage model ([0.42 vs. 0.3 MPa]; p = 0.004). The contact area was significantly smaller in the dysplasia model than in the neutral coverage model ([250.7 vs. 345.0 mm2]; p = 0.004). No significant differences were observed in contact pressure or area between the neutral and over-coverage models. Conclusions Insufficient acetabular coverage in the dysplasia model demonstrated higher contact pressure and smaller contact area than the neutral model. Conversely, the contact pressure and area in the over-coverage model did not differ significantly from those in the normal model. Therefore, surgeons should note that acetabular coverage overcorrection has limited effect; normalization is crucial during periacetabular osteotomy

Phase II trial of eribulin mesylate as a first- or second-line treatment for locally advanced or metastatic breast cancer: a multicenter, single-arm trial

Abstract Background Eribulin mesylate is currently indicated as a sequential monotherapy to be administered after two chemotherapeutic regimens, including anthracycline and taxane treatments, for treatment of metastatic breast cancer. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of eribulin as a first- or second-line treatment for patients with metastatic breast cancer. Methods The primary objective was to determine the overall response rate. Secondary objectives were to evaluate progression-free survival and the safety profile. Patients were scheduled to receive eribulin mesylate 1.4 mg/m2 intravenously on days 1 and 8 of a 21-day cycle. Patients received the study treatment unless disease progression, unacceptable toxicity, or a request to discontinue from the patient and/or investigator eventuated. Results Between December 2012 and September 2015, 32 patients with metastatic breast cancer were enrolled at 10 participating clinical institutions in Japan, and toxicity and response rates were evaluated. The overall response rate was 43.8% (95% confidence interval [CI] 26.5–61.0). The clinical benefit and tumor control rates were 56.3% (95% CI 39.0–73.5) and 78.1% (95% CI 63.8–92.5), respectively. Median progression-free survival was 8.3 months (95% CI 7.1–9.4). A subgroup analysis did not identify any factors affecting the efficacy of eribulin. The most common adverse events were neutropenia (71.9%), alopecia (68.7%), and peripheral neuropathy (46.9%). As a first- or second-line therapy, eribulin showed sufficient efficacy for metastatic breast cancer compared with taxane and capecitabine treatment in previous clinical trials. The safety profile of eribulin was acceptable. Conclusions Eribulin may be another option for first-line chemotherapeutic regimens for metastatic breast cancer. Trial registrations This trial was retrospectively registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (ID number: UMIN000010334). Date of trial registration: April 1st, 2013

Efficacy of Mepolizumab for Long-term Treatment in Patients with Severe Asthma

Mepolizumab is a monoclonal antibody against interleukin-5 used for the treatment of severe asthma. The effect of long-term mepolizumab administration and its persistence in clinical practice is poorly understood. Thus, this study aimed to investigate the effect of long-term administration of mepolizumab in patients with severe asthma. Mepolizumab was administered to 20 patients with severe asthma. We then prospectively followed the patients for 104 weeks to investigate the efficacy of long-term mepolizumab administration in clinical practice. Eleven patients were evaluated for 104 weeks. Mepolizumab administration reduced asthma exacerbations in a year from 52 to 104 weeks and improved asthma control in every period as assessed by questionnaires. Also, blood eosinophil counts decreased at every point, and blood basophil counts decreased at 104 weeks. We compared various parameters among the 11 patients who continued administration for more than 104 weeks and 7 patients who discontinued treatment due to ineffectiveness. Significant differences were observed in disease duration, maximum expiratory flow at 50%, and blood basophil count. Long-term mepolizumab administration improved asthma symptoms in patients with severe asthma and reduced the frequency of exacerbations

Practical Liposomal Formulation for Taxanes with Polyethoxylated Castor Oil and Ethanol with Complete Encapsulation Efficiency and High Loading Efficiency

Taxanes including paclitaxel and docetaxel are effective anticancer agents preferably sufficient for liposomal drug delivery. However, the encapsulation of these drugs with effective amounts into conventional liposomes is difficult due to their high hydrophobicity. Therefore, an effective encapsulation strategy for liposomal taxanes has been eagerly anticipated. In this study, the mixture of polyethoxylated castor oil (Cremophor EL) and ethanol containing phosphate buffered saline termed as CEP was employed as a solvent of the inner hydrophilic core of liposomes where taxanes should be incorporated. Docetaxel-, paclitaxel-, or 7-oxacetylglycosylated paclitaxel-encapsulating liposomes were successfully prepared with almost 100% of encapsulation efficiency and 29.9, 15.4, or 29.1 mol% of loading efficiency, respectively. We then applied the docetaxel-encapsulating liposomes for targeted drug delivery. Docetaxel-encapsulating liposomes were successfully developed HER2-targeted drug delivery by coupling HER2-specific binding peptide on liposome surface. The HER2-targeting liposomes exhibited HER2-specific internalization and enhanced anticancer activity in vitro. Therefore, we propose the sophisticated preparation of liposomal taxanes using CEP as a promising formulation for effective cancer therapies