Phosphorus recovery from the sludge generated from a continuous bipolar mode electrocoagulation (CBME) system.

Phosphorus is known to be a limited non-renewable resource. Phosphorus is obtained from phosphate rock, which is likely to be depleted in the next few decades. Therefore, it is very important to find alternate sources of phosphorus from which phosphorus can be recycled and recovered. This study focuses on the recovery of phosphorus from the sludge generated from a continuous bipolar mode electrocoagulation (CBME) system, used for treating a palm oil mill effluent (POME). The sludge generated from the CBME system is leached with oxalic acid and sulphuric acid for phosphorus recovery with and without thermal treatment. Acid leaching was carried out at various time intervals using various liquid/solid (L/S) ratios of acids and sludge. The CBME system caused a 73% removal of phosphorus from POME, where phosphorus is precipitated in sludge as iron phosphates or adsorbed as phosphates depending on the pH in the system. Acid leaching resulted in nearly 85% recovery of phosphorus with both sulphuric acid and oxalic acid for sludge combusted at 900 °C. Statistical analysis was carried out to find the significance of the operational conditions on the phosphorus yield. Acid leaching results in the formation of orthophosphates, which can be used as a raw material for synthesis of chemical fertilizers.

Chapter Seven - When Phosphorylation Encounters Ubiquitination: A Balanced Perspective on IGF-1R Signaling.

Cell-surface receptors govern the critical information passage from outside to inside the cell and hence control important cellular decisions such as survival, growth, and differentiation. These receptors, structurally grouped into different families, utilize common intracellular signaling-proteins and pathways, yet promote divergent biological consequences. In rapid processing of extracellular signals to biological outcomes, posttranslational modifications offer a repertoire of protein processing options. Protein ubiquitination was originally identified as a signal for protein degradation through the proteasome system. It is now becoming increasingly recognized that both ubiquitin and ubiquitin-like proteins, all evolved from a common ubiquitin structural superfold, are used extensively by the cell and encompass signal tags for many different cellular fates. In this chapter we examine the current understanding of the ubiquitin regulation surrounding the insulin-like growth factor and insulin signaling systems, major members of the larger family of receptor tyrosine kinases (RTKs) and key regulators of fundamental physiological and pathological states.

The real impact of telaprevir dosage on the antiviral and side effects of telaprevir, pegylated interferon and ribavirin therapy for chronic hepatitis C patients with HCV genotype 1.

Triple therapy with telaprevir, pegylated interferon and ribavirin has been reported to improve antiviral efficacy but have potentially severe adverse effects in patients with chronic hepatitis C. To avoid the severe effects of telaprevir, lowering the dose has been suggested. However, impact of dosage changes on antiviral and adverse effects remains unclear. One hundred and sixty-six Japanese patients with HCV genotype 1 were treated with triple therapy. The drug exposure of each medication was calculated by averaging the dose actually taken. The overall SVR rate was 82%. The telaprevir discontinuation rate was 26%. The factors associated with discontinuation were an older age (≥65 y.o.) and a higher average dose during treatment. The telaprevir discontinuation rates were 42%, 25% and 14% in patients at ≥35, 25-35 and <25 mg/kg/day of telaprevir and 58% in older patients at ≥35 mg/kg/day of TVR. The factors associated with SVR were treatment-naïve, relapse to previous treatment, higher average telaprevir dose during treatment and completion of treatment. The SVR rate was higher, at 91%, in patients at 25-35 mg/kg/day of telaprevir than the 71% and 78% observed in those at <25 and ≥35 mg/kg/day of drug. In Japanese patients, a mean telaprevir dose of 25-35 mg/kg/day during treatment can augment its efficacy in triple therapy for patients with HCV genotype 1.

Risk factors for hepatocellular carcinoma in hepatitis C patients with normal alanine aminotransferase treated with pegylated interferon and ribavirin.

Pegylated interferon (Peg-IFN) plus ribavirin combination therapy is effective in patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase levels (NALT). However, it remains unclear whether the risk of hepatocellular carcinoma (HCC) incidence is actually reduced in virological responders. In this study, HCC incidence was examined for 809 patients with NALT (ALT ≤ 40 IU/mL) treated with Peg-IFN alpha-2b and ribavirin for a mean observation period of 36.2 ± 16.5 months. The risk factors for HCC incidence were analysed by Kaplan-Meier method and Cox proportional hazards model. On multivariate analysis among NALT patients, the risk of HCC incidence was significantly reduced in patients with sustained virological response (SVR) or relapse compared with those showing nonresponse (NR) (SVR vs NR, hazard ratio (HR): 0.16, P = 0.009, relapse vs NR, HR: 0.11, P = 0.037). Other risk factors were older age (≥65 years vs <60 years, HR: 6.0, P = 0.032, 60-64 vs <60 years, HR: 3.2, P = 0.212) and male gender (HR: 3.9, P = 0.031). Among 176 patients with PNALT (ALT ≤ 30 IU/mL), only one patient developed HCC and no significant risk factors associated with HCC development were found. In conclusion, antiviral therapy for NALT patients with HCV infection can lower the HCC incidence in responders, particularly for aged and male patients. The indication of antiviral therapy for PNALT (ALT ≤ 30 IU/mL) patients should be carefully determined.

Prototyping sensor network system for automatic vital signs collection. Evaluation of a location based automated assignment of measured vital signs to patients.

OBJECTIVE: Development of a clinical sensor network system that automatically collects vital sign and its supplemental data, and evaluation the effect of automatic vital sensor value assignment to patients based on locations of sensors. METHODS: The sensor network estimates the data-source, a target patient, from the position of a vital sign sensor obtained from a newly developed proximity sensing system. The proximity sensing system estimates the positions of the devices using a Bluetooth inquiry process. Using Bluetooth access points and the positioning system newly developed in this project, the sensor network collects vital sign and its 4W (who, where, what, and when) supplemental data from any Bluetooth ready vital sign sensors such as Continua-ready devices. The prototype was evaluated in a pseudo clinical setting at Kyoto University Hospital using a cyclic paired comparison and statistical analysis. RESULTS: The result of the cyclic paired analysis shows the subjects evaluated the proposed system is more effective and safer than POCS as well as paper-based operation. It halves the times for vital signs input and eliminates input errors. On the other hand, the prototype failed in its position estimation for 12.6% of all attempts, and the nurses overlooked half of the errors. A detailed investigation clears that an advanced interface to show the system's "confidence", i.e. the probability of estimation error, must be effective to reduce the oversights. CONCLUSIONS: This paper proposed a clinical sensor network system that relieves nurses from vital signs input tasks. The result clearly shows that the proposed system increases the efficiency and safety of the nursing process both subjectively and objectively. It is a step toward new generation of point of nursing care systems where sensors take over the tasks of data input from the nurses.

The treatment of refractory atlanto-axial rotatory fixation using a halo vest: results of a case series involving seven children.

We reviewed seven children with torticollis due to refractory atlanto-axial rotatory fixation who were treated in a halo vest. Pre-operative three-dimensional CT and sagittal CT imaging showed deformity of the superior articular process of C2 in all patients. The mean duration of halo vest treatment was 67 days (46 to 91). The mean follow-up was 34 months (8 to 73); at the latest review six patients demonstrated remodelling of the deformed articular process. The other child, who had a more severe deformity, required C1-2 fusion. We suggest that patients with atlanto-axial rotatory fixation who do not respond to conservative treatment and who have deformity of the superior articular process of C2 should undergo manipulative reduction and halo-vest fixation for two to three months to induce remodelling of the deformed superior articular process before C1-2 fusion is considered.

A comparative analysis of incident reporting lag times in academic medical centres in Japan and the USA.

BACKGROUND: Delays in reporting of medical errors may signal deficiencies in the performance of hospital-based incident reporting. We sought to understand the characteristics of hospitals, providers and patient injuries that affect such delays. SETTING AND METHODS: All incident reports filed between May 2004 and August 2005 at the Kyoto University Hospital (KUH) in Japan and the Brigham and Women's Hospital (BWH) in the USA were evaluated. Lag time between each event and the submission of an incident report were computed. Multivariable Poisson regression with overdispersion, to control for previously described confounding factors and identify independent predictors of delays, was used. RESULTS: Unadjusted lag times were significantly longer for physicians than other reporters (3.6 vs 1.8 days, p < 0.0001), longer for major than minor events (4.1 vs 1.9 days, p = 0.0006) and longer at KUH than at BWH (3.1 vs 1.0 days, p < 0.0001). In multivariable analysis, lag times at KUH remained nearly three times longer than at BWH (incidence-rate ratio 2.95, 95% CI 2.84 to 3.06, p < 0.0001). CONCLUSIONS: Lag time provides a novel and useful metric for evaluating the performance of hospital-based incident reporting systems. Across two very different health systems, physicians reported far fewer events, with significant delays compared with other providers. Even after controlling for important confounding factors, lag times at KUH were nearly triple those at BWH, suggesting significant differences in the performance of their reporting systems, potentially attributable to either the ease of online reporting at BWH or to the greater attention to patient safety reporting in that hospital.

Factors affecting efficacy in patients with genotype 2 chronic hepatitis C treated by pegylated interferon alpha-2b and ribavirin: reducing drug doses has no impact on rapid and sustained virological responses.

Reducing the dose of drug affects treatment efficacy in pegylated interferon (Peg-IFN) and ribavirin combination therapy for patients with hepatitis C virus (HCV) genotype 1. The aim of this study was to investigate the impact of drug exposure, as well as the baseline factors and the virological response on the treatment efficacy for genotype 2 patients. Two-hundred and fifty patients with genotype 2 HCV who were to undergo combination therapy for 24 weeks were included in the study, and 213 completed the treatment. Significantly more patients who achieved a rapid virological response (RVR), defined as HCV RNA negativity at week 4, achieved a sustained virological response (SVR) (92%, 122/133) compared with patients who failed to achieve RVR (48%, 38/80) (P < 0.0001). Multivariate logistic-regression analysis showed that only platelet counts [odds ratio (OR), 1.68; confidence interval (CI), 1.002-1.139] and RVR (OR, 11.251; CI, 5.184-24.419) were independently associated with SVR, with no correlation being found for the mean dose of Peg-IFN and ribavirin for RVR and SVR. Furthermore, in the stratification analysis of the timing of viral clearance, neither mean dose of Peg-IFN (P = 0.795) nor ribavirin (P = 0.649) affected SVR in each group. Among the patients with RVR, the lowest dose group of Peg-IFN (0.77 +/- 0.10 microg/kg/week) and ribavirin (6.9 +/- 0.90 mg/kg/day) showed 100% and 94% of SVR. Hence, RVR served as an important treatment predictor, and drug exposure had no impact on both SVR and RVR in combination therapy for genotype 2 patients.

Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin.

The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis (P = 0.002), the timing of HCV RNA negativiation (P < 0.001) and the mean doses of ribavirin (P < 0.001) were significantly associated with relapse, but those of Peg-IFN were not. Stepwise reduction of the ribavirin dose was associated with a stepwise increase in relapse rate from 11% to 60%. For patients with complete early virologic response (c-EVR) defined as HCV RNA negativity at week 12, only 4% relapse was found in patients given > or = 12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 microg/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (> or = 12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in c-EVR patients.

Pegylated interferon alpha-2b (Peg-IFN alpha-2b) affects early virologic response dose-dependently in patients with chronic hepatitis C genotype 1 during treatment with Peg-IFN alpha-2b plus ribavirin.

Chronic hepatitis C (CH-C) genotype 1 patients who achieved early virologic response have a high probability of sustained virologic response (SVR) following pegylated interferon (Peg-IFN) plus ribavirin therapy. This study was conducted to evaluate how reducing drug doses affects complete early virologic response (c-EVR) defined as hepatitis C virus (HCV) RNA negativity at week 12. Nine hundred eighty-four patients with CH-C genotype 1 were enrolled. Drug doses were evaluated independently on a body weight base from doses actually taken. From multivariate analysis, the mean dose of Peg-IFN alpha-2b during the first 12 weeks was the independent factor for c-EVR (P = 0.02), not ribavirin. The c-EVR rate was 55% in patients receiving > or = 1.2 microg/kg/week of Peg-IFN, and declined to 38% at 0.9-1.2 microg/kg/week, and 22% in patients given <0.9 microg/kg/week (P < 0.0001). Even with stratified analysis according to ribavirin dose, the dose-dependent effect of Peg-IFN on c-EVR was observed, and similar c-EVR rates were obtained if the dose categories of Peg-IFN were the same. Furthermore, the mean dose of Peg-IFN during the first 12 weeks affected HCV RNA negativity at week 24 (P < 0.0001) and SVR (P < 0.0001) in a dose-dependent manner. Our results suggest that Peg-IFN was dose-dependently correlated with c-EVR, independently of ribavirin dose. Thus, maintaining the Peg-IFN dose as high as possible during the first 12 weeks can yield HCV RNA negativity and higher c-EVR rates, leading to better SVR rates in patients with CH-C genotype 1.

Cost analysis of radiotherapy, carbon ion therapy, proton therapy and BNCT in Japan.

The purpose of this study was to estimate the financial costs to start BNCT as a clinical treatment in a hospital. To evaluate more accurate data on the precise costs of BNCT, we analyzed the costs of conventional radiotherapy, carbon ion and proton therapy and compare them to BNCT. An aggregate cost calculation of accelerator, buildings, equipments and staff requirements was performed.

Nipponium as a new element (Z=75) separated by the Japanese chemist, Masataka Ogawa: a scientific and science historical re-evaluation.

This review article deals with a new element 'nipponium' reported by Masataka Ogawa in 1908, and with its scientific and science historical background. Ogawa positioned nipponium between molybdenum and ruthenium in the periodic table. From a modern chemical viewpoint, however, nipponium is ascribable to the element with Z=75, namely rhenium, which was unknown in 1908. The reasons for this corrected assignment of nipponium are (1) its optical spectra, (2) its atomic weight when corrected, (3) its relative abundance in molybdenite, the same being true with rhenium. Recently some important evidence was found among the Ogawa's personal collection preserved by his family. Deciphering the X-ray spectra revealed that the measured spectra of the nipponium sample that Ogawa brought from University College, London clearly showed the presence of the element 75 (rhenium). Thus was resolved the mysterious story of nipponium, which had continued for almost a century. It is concluded that nipponium was identical to rhenium.

Three-dimensional images for surgical plan of giant sacral schwannoma.

OBJECTIVE: Documentation of three-dimensional (3D) images of a giant sacral schwannoma with intrapelvic expansion. SETTING: Nagoya University, Nagoya, Japan. RESULTS: 3D computed tomography (3D CT) showed a destructed bony region clearly. 3D CT angiography clarified the positional relationship between tumor and iliac arteries. Resection procedure was safely completed based on these 3D evaluations. CONCLUSION: 3D images were helpful to make a surgical plan and to complete this complicated resection combined with sacroiliac reconstruction.

FK506-associated limbic injury following umbilical cord blood transplantation.

A 5-year-old girl with Ph-positive chronic myelogenous leukemia, who underwent umbilical cord blood transplantation, developed two episodes of electrical status epilepticus while receiving tacrolimus (FK506) then cyclosporin A (CsA), as treatment against graft-versus-host disease. MRI including diffusion weighted MR imaging of the brain revealed abnormalities in the hippocampus and posterior white matter following FK506 and CsA treatment, respectively. While posterior white matter injury has been described with both FK506 and CsA, no previous report describes hippocampal injury from either drug. The MRI changes in the hippocampus in our case suggest possible increased susceptibility to hippocampal injury with FK506.

Significance of serum soluble Fas antigen level in chronic hepatitis C patients treated with interferon: relationship to the therapeutic response.

BACKGROUND AND AIM: Fas system-mediated cytotoxicity is thought to be involved in the development of liver injury in hepatitis C virus (HCV) infection. In this study, we investigated serum soluble Fas antigen levels in chronic hepatitis C patients treated with interferon and their correlation with the therapeutic response. METHODS: The subjects were 67 chronic hepatitis C patients who underwent a 24-week course of alpha-interferon therapy. Patients were categorized into three groups; sustained responders (n = 22), transient responders (n = 24), and non-responders (n = 21), according to changes in the serum alanine aminotransferase level during and after therapy. The viral genotype, viremic level and diversity in the hypervariable region were examined before therapy. Serum soluble Fas antigen levels were assayed by using serum samples taken at the beginning and the end of therapy. RESULTS: In the univariate analysis, serum soluble Fas antigen levels tended to be higher in non-responders (10.0 +/- 3.4 ng/mL) than in sustained responders (8.5 +/- 3.0 ng/mL) and transient responders (8.2 +/- 2.1 ng/mL; P = 0.13 and P < 0.05). The non-response to therapy was observed in eight of the 15 (53%) patients with serum soluble Fas antigen > or = 11 ng/mL, compared with 13 of the 52 (25%) patients with serum soluble Fas antigen < 11 ng/mL (P < 0.05). As for the multivariate analysis, the only significant factor contributing to the sustained response was a low HCV viremic level (P = 0.0046). Significant factors contributing to the non-response were a high serum alanine aminotransferase (P = 0.0407) and a high serum soluble Fas antigen level (P = 0.0483). CONCLUSIONS: High production levels of soluble Fas antigen may be associated with a poor response to interferon therapy in chronic hepatitis C patients.

A designed antagonist of the thyroid hormone receptor.

We synthesized an analogue of the thyromimetic GC-1 bearing the same hydrophobic appendage as the estrogen receptor antagonist ICI-164,384. While having reduced affinity for the thyroid hormone receptors compared to GC-1, it behaves in a manner consistent with a competitive antagonist in a transactivation assay.

Histologic analysis of the implanted cartilage in an exact-fit osteochondral transplantation model.

PURPOSE: Osteochondral transplantation is one of the useful treatments for articular cartilage defect. However, the histologic change of the implanted cartilage has not been reported in detail. We investigated the histology of exact-fit osteochondral transplants used to repair articular cartilage defects in an animal model. TYPE OF STUDY: This was a nonrandomized control study using an animal model. METHODS: Sixteen skeletally mature female Japanese white rabbits were used in the study. The region of the femoral groove was selected as the site for the osteochondral defect. A full-thickness cylindrical defect (7 mm in diameter and 7 mm in depth) through the articular cartilage and into the subchondral bone was made using the Osteochondral Autograft Transfer System (Arthrex, Naples, FL). The entire osteochondral fragment was removed and then returned to its original site in the femoral condyle precisely. Thus, the defect was repaired with an autogenous osteochondral transplantation of exactly the same size and configuration as the defect. Specimens were obtained 2, 4, 12, and 24 weeks postoperatively and were analyzed both macroscopically and histologically. RESULTS: Macroscopically, there was smooth continuity of the articular surface and the integration of the graft to the normal host cartilage. However, histologic examination showed that the layer of the grafted cartilage was thicker than that of the normal host cartilage and the extracellular matrix of the implanted cartilage exhibited a stronger staining pattern with safranin-O fast green than the normal cartilage. Cell density was higher in the grafted cartilage, particularly in the middle and the deep zones. Round and polygonal hypertrophic clusters of chondrocytes were observed in the middle and deep zones of the grafted cartilage. CONCLUSIONS: The histologic properties of the exact-fit implanted cartilage were different from that of normal articular cartilage. Further investigation of mechanical and structural properties of grafted cartilage is necessary to verify the long-term effects of osteochondral transplantation.

Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance.

The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-gamma prior to initiation of interferon-alpha treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-alpha treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-gamma (1 MIU/day) was administered daily for 14 days followed by natural IFN-alpha (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-alpha treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-gamma administration, and tended to return to the pretreatment level after the start of IFN-alpha administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN-gamma prior to the initiation of IFN-alpha treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.

De novo malignant transformation of giant cell tumor of bone.

Two cases of malignant lesions are reported, both of which arose secondary to an originally benign giant cell tumor (GCT) of bone. The first case was a typical benign GCT, which occurred in the left proximal tibia of a 31-year-old woman. The tumor was treated by curettage and bone grafting. However, it recurred twice during 15 years of follow-up. The second recurrence showed that the lesion histologically had turned into malignant fibrous histiocytoma. The second case also started as an initially benign GCT that arose in the left distal femur of a 41-year-old man. The patient underwent curettage and bone grafting. The lesion recurred 13 years postoperatively. The histological appearance of the recurrent tumor showed it to be an osteogenic sarcoma. In both patients, radiation and never been given. Malignant transformation has rarely been reported in patients with GCT of bone who have not received radiation treatment.