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Chih-Weim Hsiang,1 Wen-Yen Huang,2,3 Jen-Fu Yang,2 Po-Chien Shen,2 Yang-Hong Dai,2 Ying-Fu Wang,2 Chun-Shu Lin,2 Wei-Chou Chang,1 Cheng-Hsiang Lo2 1Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 3Institute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanCorrespondence: Cheng-Hsiang LoDepartment of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec 2, Cheng-Gong Road, Neihu, Taipei, 114, TaiwanTel +886-2-87927122Fax +886-2-66002357Email lsir183@yahoo.com.twPurpose: Immune response to antitumor therapies has been correlated with oncologic outcomes. This study aimed to determine whether dynamic changes in immune parameters could predict survival outcomes and assess their relationship with liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT).Methods: Data on pre- and post-SBRT (within 3 months) peripheral blood cell counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were retrospectively collected. Kinetic changes in these immune parameters and delta-NLR (dNLR) and delta-PLR (dPLR) in response to SBRT were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared based on baseline NLR/PLR and dNLR/dPLR. Additionally, the association of these dynamic measures with liver toxicity was determined.Results: The study included 93 patients with a median 10.7-month follow-up. Significant increases in NLR (p< 0.001) and PLR (p=0.003) were observed after SBRT. In the multivariable analysis, elevated pre-SBRT NLR (p< 0.001) and dNLR (p=0.011) were predictive of worse OS. dNLR was not associated with PFS. Neither PLR nor dPLR was predictive of survival outcomes. Patients with Child–Turcotte–Pugh class B had higher dNLR and greater risk of liver toxicity than class A counterparts. Receiver operating characteristic curve analysis found that dNLR ≥ 1.9 was an optimal cut-off value for determining liver toxicity risk (35.1% vs 7.5%, p=0.002).Conclusion: Baseline NLR and dNLR can complementarily predict OS in HCC patients treated with SBRT. Elevated dNLR is associated with worse OS and development of liver toxicity, possibly through their relationship with baseline liver function. Dynamic changes in NLR should be monitored in HCC care.Keywords: hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, stereotactic body radiotherapy, liver toxicity

We study the spin-exotic J(PC)=1(-+) amplitude in single-diffractive dissociation of 190 GeV/c pions into pi(-)pi(-)pi(+) using a hydrogen target and confirm the pi(1)(1600) -> rho(770)pi amplitude, which interferes with a nonresonant 1(-+) amplitude. We demonstrate that conflicting conclusions from previous studies on these amplitudes can be attributed to different analysis models and different treatment of the dependence of the amplitudes on the squared four-momentum transfer and we thus reconcile these experimental findings. We study the nonresonant contributions to the pi(-)pi(-)pi(+) final state using pseudodata generated on the basis of a Deck model. Subjecting pseudodata and real data to the same partial-wave analysis, we find good agreement concerning the spectral shape and its dependence on the squared four-momentum transfer for the J(PC)=1(-+) amplitude and also for amplitudes with other J(PC) quantum numbers. We investigate for the first time the amplitude of the pi(-)pi(+) subsystem with J(PC)=1(--) in the 3 pi amplitude with J(PC)=1(-+) employing the novel freed-isobar analysis scheme. We reveal this pi(-)pi(+) amplitude to be dominated by the rho(770) for both the pi(1)(1600) and the nonresonant contribution. These findings largely confirm the underlying assumptions for the isobar model used in all previous partial-wave analyses addressing the J(PC)=1(-+) amplitude.

Wei-Chou Chang,1 Hsian-He Hsu,1 Sung-Hua Chiu,1 Wen-Yen Huang,2 Cheng-Hsiang Lo,2 Hsuan-Hwai Lin,3 Pei-Ching Huang,4 Yu-Lueng Shih,3 Yung-Liang Wan4 1Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 2Department of Radiation Oncology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 3Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 4Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, TaiwanCorrespondence: Yung-Liang WanDepartment of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, TaiwanEmail ylw0518@cgmh.org.twAbstract: Drug-eluting beads transarterial chemoembolization (DEB-TACE) is an alternative to conventional lipiodol-based TACE (cTACE) to treat hepatocellular carcinoma (HCC). With the advancement in pharmacology, small-caliber DEB-TACE (< 100 μm) has been introduced since 2016. For the treatment of hepatic neoplasms or HCC, there is a tendency to use smaller beads by DEB-TACE to achieve more extensive tumor necrosis and a significant reduction in liver toxicity in comparison with that caused by cTACE. However, the indications and potential complications of small-caliber DEB-TACE remain uncertain and have not been well established, due to lack of randomized phase III clinical trials. Instead of systematic or meta-analysis review, this narrative review article describes the suggested indications and contraindications of DEB-TACE with small DEBs, benefit of super-selective embolization of the feeding arteries and the recommended selection of small-caliber DEB. This review was approved by the institutional review board (File Number: 1-105-05-158).Keywords: chemoembolization, HCC, TACE, DEB-TACE, liver, review

BACKGROUND: Haloperidol remains a frequently prescribed first-generation antipsychotic. However, haloperidol-associated mortality risk by all causes, cardiovascular disease (CVD), and pneumonia compared with other antipsychotics is unknown. OBJECTIVE: This study investigated the mortality risk associated with long-term haloperidol treatment versus that with other antipsychotics. METHODS: We identified incident antipsychotic users from 2004 to 2014 in the Clinical Data Analysis and Reporting System (CDARS), a population-based clinical database managed by the Hong Kong Hospital Authority. We included patients who were aged ≥ 18 and received antipsychotics for any indication apart from terminal illnesses or management of acute behavioural disturbance. Patients on haloperidol and other antipsychotic agents (risperidone, quetiapine, olanzapine, chlorpromazine, aripiprazole, sulpiride, amisulpride, or trifluoperazine) were matched by propensity score. Hazard ratios (HRs) for all-cause mortality and death due to CVD and pneumonia were estimated with 95% confidence intervals (CIs) using a Cox proportional hazards model. RESULTS: In total, 136,593 users of antipsychotics were included. During a mean follow-up of 3.2 years, the incidence of all-cause mortality ranged from 186.8/1000 person-years for haloperidol to 10.4/1000 person-years for trifluoperazine. The risk of all-cause mortality was lower with non-haloperidol antipsychotics than with haloperidol, with HRs ranging from 0.68 (95% CI 0.64-0.72 [chlorpromazine]) to 0.43 (95% CI 0.36-0.53 [trifluoperazine]). Risperidone, quetiapine, sulpiride, chlorpromazine, aripiprazole, and trifluoperazine were associated with a significantly lower risk of pneumonia-related mortality. A significantly lower risk of CVD mortality was observed for risperidone, sulpiride, chlorpromazine, and quetiapine. CONCLUSION: Haloperidol was associated with increased overall mortality when compared with other antipsychotics in long-term follow-up. Treatment with haloperidol should be carefully considered, especially in older patients and patients at risk of CVD or pneumonia, since the risk of death appears to be lower with non-haloperidol agents.

Chun-Bing Chen,1–6 Ming-Ying Wu,1–4 Chau Yee Ng,1–5 Chun-Wei Lu,1–6 Jennifer Wu,1–4,6 Pei-Han Kao,1–4,6 Chan-Keng Yang,4–7 Meng-Ting Peng,4,6–7 Chen-Yang Huang,4,6–7 Wen-Cheng Chang,4,6–7 Rosaline Chung-Yee Hui,1–4 Chih-Hsun Yang,1–4 Shun-Fa Yang,8,9 Wen-Hung Chung,1–4,6,10,11 Shih-Chi Su1–4,10 1Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; 2Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan; 3Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan; 4College of Medicine, Chang Gung University, Taoyuan, Taiwan; 5Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 6Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; 7Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 8Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 9Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; 10Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; 11Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China Abstract: With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5–91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management. Keywords: acute generalized exanthematous pustulosis, drug rash, eosinophilia, Stevens–Johnson syndrome, toxic epidermal necrolysis, targeted therapy, immunotherapy

Chih-Jen Yang,1 Wen-I Liao,1 Zun-Cheng Tang,2 Jen-Chun Wang,1 Chien-Hsing Lee,3 Wei-Chou Chang,4 Chin-Wang Hsu,5,6 Shih-En Tang,7 Shih-Hung Tsai1 1Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, 2Department of Biological Imaging and Radiological Science, National Yang-Ming University, 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, 4Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, 5Department of Emergency Medicine, School of Medicine, College of Medicine, 6Department of Emergency and Critical Medicine, Wan Fang Hospital, Taipei Medical University, 7Division of Pulmonary and Critical Care, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Abstract: Acute hyperglycemia is a common finding in patients presenting to emergency departments (EDs) with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Several studies have argued against the association between hyperglycemia at admission and adverse outcomes in patients with diabetes and an acute illness. Recent studies have shown that glucose-related variables (eg, glycemic gaps and stress hyperglycemia ratios) that are adjusted for glycated hemoglobin levels can indicate the severity of a variety of diseases. The objective of this study was to assess whether these hemoglobin A1c (HbA1c)-based adjusted average glycemic variables were associated with unfavorable outcomes in patients admitted to a hospital with AECOPD. We found that 1) pulmonary infection is a major risk factor for AECOPD; 2) a higher glycemic gap and modified stress hyperglycemia ratio were associated with the development of acute respiratory failure (ARF) in patients with diabetes admitted to an ED because of AECOPD; and 3) the glycemic gap and modified stress hyperglycemia ratio had superior discriminative power over acute hyperglycemia and HbA1c for predicting the development of ARF, although the HbA1c-adjusted glycemic variables alone were not independent risk factors for ARF. Keywords: chronic obstructive pulmonary disease, diabetes mellitus, acute respiratory failure, glycated hemoglobin, hyperglycemia, glycemic gap, stress hyperglycemia ratio

The SeaQuest spectrometer at Fermilab was designed to detect oppositely-charged pairs of muons (dimuons) produced by interactions between a 120 GeV proton beam and liquid hydrogen, liquid deuterium and solid nuclear targets. The primary physics program uses the Drell–Yan process to probe antiquark distributions in the target nucleon. The spectrometer consists of a target system, two dipole magnets and four detector stations. The upstream magnet is a closed-aperture solid iron magnet which also serves as the beam dump, while the second magnet is an open aperture magnet. Each of the detector stations consists of scintillator hodoscopes and a high-resolution tracking device. The FPGA-based trigger compares the hodoscope signals to a set of pre-programmed roads to determine if the event contains oppositely-signed, high-mass muon pairs.

This write-up document is a summary of International workshop on the project for the extended hadron experimental facility which was held from March 26 to 28, 2018 at KEK Tokai Campus. This document is a collection of Letter Of Intents (LOIs) related to the proposed beam lines in the extended hadron experimental facility at J-PARC.

Abnormal risky decision making may represent an important factor contributing to functional impairment in psychotic disorders. Previous research revealed impaired decision making under risk in patients with chronic schizophrenia. However, risky decision making is under-studied in the early course of illness. We examined risky decision making in 33 patients with early non-affective psychosis and 32 demographically matched controls, using two well-validated experimental paradigms, balloon analogue risk task (BART) and Risky-Gains task (RGT), which modeled and assessed actual risk-taking behaviors in deliberative and time-pressured decision-making situations, respectively. Our results showed that patients exhibited suboptimal decision making on the BART and were more risk averse than controls by having fewer average balloon pumps in non-burst trials, lower explosion rate and lower total points gained. On the RGT, patients also behaved more conservatively than controls, with lower overall rate in choosing the risky option. Intriguingly, patients performed comparably to controls in adjusting risk-taking pattern following punished trials, suggesting relatively preserved sensitivity to punishment in early psychosis. Risk-taking measures showed no significant correlations with any symptom dimensions, impulsivity traits, cognitive functions or antipsychotic treatment after correcting for multiple comparisons. This study is the first to investigate risk-taking propensity in early psychosis based on BART/RGT performance, and consistently indicate that patients with early psychosis displayed altered risky decision making with increased risk aversion relative to healthy participants. Further investigation is warranted to clarify the longitudinal course of aberrant risky decision making and its relationship with functional outcome in early psychosis.

Chien-Shu Wang,1 Jo Yung-Wei Wu,2 Wei-Chung Chang,3 Shu-Ping Chuang1 1Department of Psychiatry, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; 2Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Hsin-Jia Psychotherapy Clinic, Taitung County, Taiwan Aim: The study aimed to investigate the relationship among sociodemographic factors, neurocognitive factors, self-esteem, and health locus of control in patients diagnosed with schizophrenia. We examined the self-esteem, internal health locus of control, and external health locus of control through sociodemographic and neurocognitive factors. Methods: Forty-six schizophrenic patients and 31 healthy residents from the community or hospital were recruited as the control group. All subjects participated in the self-esteem questionnaire, health locus of control questionnaire, and a series of neuropychological measures. Results: Multiple regression analysis revealed that inhibition of attention and external health locus of control were predictors for self-esteem (r=−0.30, P

Pei-Chun Hsieh,1 Shu-Min Chen,1–3 Yao-Hong Guo,1 Ta-Shen Kuan,1,2 Wei-Jang Yen,1 Wen-Chen Chang,1 Yu-Ching Lin1–3 1Department of Physical Medicine and Rehabilitation, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; 2Department of Physical Medicine and Rehabilitation, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; 3Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan, Republic of China Abstract: Dystonia is a rare manifestation of multiple sclerosis (MS), but it always interferes with the functional performance and quality of life. We report a rare case of long-lasting paroxysmal dystonia associated with MS. The patient was a 40-year-old woman with relapsing- remitting MS for 6 years. During the latest attack of MS, she suffered from long-lasting paroxysmal dystonia in her left hand. Despite treatment with pulse high-dose intravenous methylprednisolone, interferon, and baclofen, along with occupational therapy, the dystonia persisted and significantly bothered her daily activities. Finally, she was treated with oral acetazolamide (250 mg, three times a day for 4 days), which was very effective for the control of her dystonia. The dystonic movement subsided without recurrence in a follow-up of 17 months. We advocate this effective and safe treatment for patients with paroxysmal dystonia associated with MS. Keywords: multiple sclerosis, dystonia, acetazolamide, movement disorders, rehabilitation

IMPORTANCE: There is a concern that Helicobacter pylori therapy containing clarithromycin might be associated with acute neuropsychiatric events. OBJECTIVE: To examine the association between H pylori therapy containing clarithromycin and acute neuropsychiatric events. DESIGN, SETTING, AND PARTICIPANTS: A self-controlled case series study was conducted using the Clinical Data Analysis and Reporting System database in Hong Kong to explore any association. The exposure of interest was H pylori therapy containing clarithromycin in the outpatient setting. Study patients, 18 years or older at cohort entry, must have had both exposure to H pylori therapy containing clarithromycin and their first recorded neuropsychiatric events between January 1, 2003, and December 31, 2012. A post hoc nested case-control analysis was also performed in patients receiving H pylori therapy containing clarithromycin. MAIN OUTCOMES AND MEASURES: The primary outcome was composite neuropsychiatric events, while secondary outcomes were psychotic events and cognitive impairment. Risk periods in the self-controlled case series analysis were defined as 14-day preexposure period, current use (days 1-14 since prescription start date) and recent use (days 15-30). Age-adjusted incidence rate ratios (IRR) were estimated using the conditional Poisson regression. RESULTS: Of 66 559 patients who had at least 1 outpatient prescription of H pylori therapy containing clarithromycin. Their mean (SD) age at cohort entry was 50.8 (14.8 years); their mean age at first exposure was 55.4 (14.8) years, and 30 910 were male (46.4%). A total of 1824 patients had their first recorded composite neuropsychiatric events during the study period. An increased IRR of 4.12 (35 composite neuropsychiatric events during 72 person-years; 95% CI, 2.94-5.76) during current use was observed but not in recent use (9 events during 82 person-years; IRR, 0.95; 95% CI, 0.49-1.83) and 14-day preexposure period (14 events during 72 person-years; IRR, 1.63; 95% CI, 0.96-2.77) vs baseline (1766 events during 16 665 person-years). Similarly, both the risk of psychotic events and cognitive impairment increased during current use vs baseline, although this subsequently returned to baseline incidence levels during recent use. The crude absolute risks of composite neuropsychiatric events, psychotic events, and cognitive impairment during current use were 0.45, 0.12, and 0.12 per 1000 prescriptions, respectively. The nested case-control analysis also gave similar results to that of the self-controlled case series analysis. CONCLUSIONS AND RELEVANCE: This study shows evidence of a short-term increased risk of neuropsychiatric events associated with H pylori therapy containing clarithromycin.

M-J. Lee, C. J. Chen, W-C. Huang, M-C. Huang, W-C. Chang, H-S. Kuo, M-J. Tsai, Y-L. Lin and H. Cheng (2011) Neuropathology and Applied Neurobiology37, 585–599 Regulation of chondroitin sulphate proteoglycan and reactive gliosis after spinal cord transection: effects of peripheral nerve graft and fibroblast growth factor 1 Aims: The combined treatment of peripheral nerve (PN) graft and fibroblast growth factor (FGF)-1 for spinal cord injury produces functional recovery, but how it affects injury events is still unknown. This project studied the effect of PN graft and FGF-1 on white matter degeneration following spinal cord injury. Methods: Rats were divided into four groups: (i) complete spinal cord transection and T8 segment removed; the remaining three groups underwent transection followed by (ii) PN grafting; (iii) supply of exogenous FGF-1; and (iv) PN grafting plus FGF-1 treatment. Chondroitin sulphate proteoglycan (CSPG) deposition, astrocytes and macrophage activation, cavity size, and calcitonin gene-related peptide and synaptophysin immunoreactivity were compared. Results: Peripheral nerve grafting increased CSPG levels compared to transection surgery alone. This CSPG was associated with the proximity to the PN graft. FGF-1 reduced CSPG deposition in grafted animals regardless of the proximity to the graft. The CSPG reduction was accompanied by reduced GFAP expression and macrophage activation. The amount of CSPG with dissociated glycosaminoglycan did not differ between groups. FGF-1 in Schwann cell–astrocyte coculture did not reduce CSPG deposition. Furthermore, the PN graft increased the calcitonin gene-related peptide immunoreactivity and altered the distribution of synaptophysin-positive axons. Conclusion: Peripheral nerve graft supported sensory re-innervation and partial protection of the grey matter, but up-regulated CSPG in the graft–stump junction compared to non-grafted rats. The reduction of CSPG was caused by FGF-1–PN synergy, and did not involve dissociation of CSPG or the suppression of a general immune response.

Aims: To investigate the in situ expression profile of glucocorticoid receptor (GR) in normal and carcinomatous tissues of the human digestive system. Methods and results: Specimens from 306 carcinomas of the human digestive tract were assayed for the expression of GR by immunohistochemistry. GR expression was strong in oesophageal squamous epithelia, pancreatic islet cells and hepatocytes, but generally weak or negative in non-squamous epithelia. Consistently, GR expression was found in a high percentage of oesophageal squamous cell carcinomas (SCC) (98.1%) and hepatocellular carcinomas (HCC) (92.9%), but rarely in gastric adenocarcinomas (7.4%) and not at all in colorectal adenocarcinomas (0%). Dexamethasone (DEX) was found to confer chemoresistance in oesophageal SCC and HCC cells, suggesting that GR expression may be biologically important in some GR-expressing carcinomas. Conclusions: Distribution of GR expression is markedly diverse among tissues of the human digestive system. The general lack of GR in adenocarcinomas contrasts with the high percentage of SCCs and HCCs expressing GR, and, along with the generation of chemoresistance by DEX, warrants prospective study of the effects of steroids on these cancers.

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This study investigated the feasibility of improving the removal of anions from a secondary effluent by coagulation/flocculation (Coag/Floc) and dissolved air flotation (DAF) using a pilot-scale wastewater reclamation plant in a high-tech industrial park. The pilot plant was equipped with units of Coag/Floc, DAF, activated carbon beds (AC), microfiltration modules (MF) and a reverse-osmosis membrane (RO). It was operated in-situ continuously for around one year to evaluate the performance of anion removal in two processes - the AC-RO process and the DAF-AC-RO process. Long-term experimental results indicated that combining Coag/Floc, DAF and AC units increased the potential of pretreatment to remove anions. The removal efficiencies in Coag/Floc-DAF units were in the order phosphatefluoridechloridesulfatesilicate. The charged complex of PACl flocs revealed a higher affinity for adsorption onto phosphate and fluoride than on chloride, sulfate and silicate. Comparison of the performance of Coag/Floc-DAF-AC units in the DAF-AC-RO process with that of a single AC unit in the AC-RO process demonstrated that adding Coag/Floc-DAF units increased the removal efficiencies of phosphate, fluoride and silicate by approximately 70.0%, 42.7% and 70.1%, respectively. Most of the phosphate and fluoride were removed in Coag/Floc-DAF units, while most of the silicate escaped from the Coag/Floc-DAF units, and was adsorbed and/or trapped in the AC unit. The quality of reclaimed water in the DAF-AC-RO process complied with the requirements of high-tech industries in cleaning processes. Combined units of Coag/Floc-DAF-AC were therefore recommended for use in pretreatment in wastewater reclamation in high-tech industrial parks.

Glucocorticoid receptor (GR) is a steroid hormone receptor that has been shown to play important roles in mammary development and differentiation, and has been implicated in breast tumourigenesis, but its precise biological significance in mammary pathophysiology remains unclear. In order to generate a comprehensive expression profile for GR in normal versus neoplastic breast tissues, GR expression was investigated in situ in 400 human breast tissue samples, comprising normal tissue and a range of benign, pre-invasive, and invasive lesions, using immunohistochemical assays. The novel expression of GR in myoepithelium, not observed in luminal epithelium, not only demonstrates expression patterns exclusive to the alpha form of oestrogen receptor and progesterone receptor and suggests distinctive functions between GR and these two important steroid hormone receptors in the breast, but may also indicate unique physiological and perhaps pathological roles for the myoepithelium in mediating the effects of glucocorticoid hormones in the breast. The strong expression of GR in metaplastic carcinomas (94.4%) and malignant phyllodes tumours (92.3%) suggests a pathogenetic role for GR, and implies that targeting GR in these tumours may have potential therapeutic application. However, studies on the roles of GR in mammary carcinogenesis should be interpreted with great caution, based on the lack of GR expression in cancer cells in the great majority (98.2%) of non-metaplastic carcinomas, which has gone unnoticed in previous studies. This marked discrepancy warrants a re-examination of the biological roles of GR in the pathophysiology of breast malignancy. The lack of methylation in the promoter region of the GR gene in all 118 non-metaplastic carcinomas, as demonstrated by methylation-specific PCR and bisulphite DNA sequencing analysis, indicates that methylation is less likely to play a role in the reduction of GR expression in non-metaplastic carcinoma of the breast.

The increase of intracellular Ca2+ concentration is an important mechanism that regulates a variety of physiological processes ranging from exocytosis to gene regulation and cell proliferation [1]. Calcium release from intracellular stores (mainly endoplasmic reticulum, ER) or calcium entry through calcium channels can be used by cells to evoke a higher level of cytosolic Ca2+ concentration. In non-excitable cells, a major pathway for Ca2+ influx is via store-operated Ca2+ channels (also known as capacitative calcium entry) [2]. The concept of Store-operated calcium (SOC) channel was first proposed by James Putney in 1986 [3]. In this model, the depletion of intracellular calcium stores triggers calcium entry across the plasma membrane. In 1992, Hoth & Penner identified the presence of this a Ca2+ release-activated Ca2+ current (CRAC) [4]. Using RNA interference (RNAi)-based approaches, STIM1, an intracellular calcium sensor, was found in 2005 [5, 6]. One year later, Orai1 (CRACM1) was discovered as an essential component of store-operated calcium channel in T cells and mast cells [7, 8]. The role of Ca2+ in cell motility has been known for a long time. There is evicence that Ca2+ influx is more important than Ca2+ release in the migration of fibroblast and breast cancer cells

Introduction. The controlled expression of many genes, including G-protein coupled receptors (GPCRs), is important for delineating gene functions in complex model systems. Binary systems for inducible regulation of transgene expression are widely used in mice. One system is the tTA/TRE expression system, composed of a tetracycline-dependent DNA binding factor and a separate tetracycline operon. However, the requirement for two separate transgenes (one for each tTA or TRE component) makes this system less amenable to models requiring directed cell targeting, increases the risk of multiple transgene integration sites, and requires extensive screening for appropriately- functioning clones. Methods. We developed a single, polycistronic tetracycline-inducible expression platform to control the expression of multiple cistrons in mammalian cells. This platform has three basic constructs: regulator, responder, and destination vectors. The modular platform is compatible with both the TetOff (tTA) and TetOn (rtTA) systems. The modular Gateway recombineering-compatible components facilitate rapidly generating vectors to genetically modify mammalian cells. We apply this system to use the elongation factor 1 (EF1) promoter to drive doxycycline-regulated expression of both the fluorescent marker mCherry and an engineered G s-coupled GPCR "Rs1" separated by a 2A ribosomal skip site. Results: We show that our combined expression construct drives expression of both the mCherry and Rs1 transgenes in a doxycycline-dependent manner. We successfully target the expression construct into the Rosa26 locus of mouse embryonic stem (ES) cells. Rs1 expression in mouse ES cells increases cAMP accumulation via both basal and ligand-induced G smechanisms and is associated with increased embryoid body size. Heterozygous mice carrying the Rs1 expression construct showed normal growth and weight, and developed small increases in bone formation that could be observed in the calvaria. Conclusions: Our results demonstrate the feasibility of a single-vector strategy that combines both the tTA and TRE tetracycline-regulated components for use in cells and mouse models. Although the EF1 promoter is useful for driving expression in pluripotent cells, a single copy of the EF1 promoter did not drive high levels of mCherry and Rs1 expression in the differentiated tissues of adult mice. These findings indicate that promoter selection is an important factor when developing transgene expression models. © 2011Hsiao et al.; licensee BioMed Central Ltd.

Session 15. Neuroimaging, Structural, This journal suppl. is abstracts for the 13th International Congress, ICOSR 2011, BACKGROUND: Both physical exercise and Yoga have been shown significant benefits in symptoms and cognitions in some mental disorders. The present study compared the effectiveness of a 12-week yoga therapy and physical exercise on neuro-cognitive function in female psychosis patients, aimed to develop a complementary treatment to improve cognitive function in patients with psychosis. METHODS: A total of 60 female psychosis patients were recruited, and randomized into three groups: a) 1 12-week yoga therapy group (n = 20), b) a 12-week physical exercise group (n = 20), and c) a waitlisted group which acted as the control group (n = 20) for 12 weeks. All participants were assessed in structural and functional brain (sMRI and fMRI), clinical symptom, neurocognition, physical fitness and quality of life both at baseline and after 12 weeks intervention. RESULTS: Out preliminary data showed significant improvements in the general health (P = .001), physical functioning (P = .001), energy (P = .034) and emotional well-being (P = .036) with the measure of SF-36 in normal female subjects after a basic level of Hatha Yoga course, each session lasted for 60 minutes, twice weekly for 6 weeks. The preliminary finding indicated that yoga therapy have a positive effect both physically and psychologically. CONCLUSION: The study results would not only facilitate our understanding of the relative effectiveness of yoga and physical exercise, but may also shed light on the future development of adjunct non-pharmacological therapy in improving neuro-cognitive functions in patients with psychosis., link_to_OA_fulltext, The 13th International Congress on Schizophrenia Research (ICOSR), Colorado Springs, CO., 2-6 April 2011. In Schizophrenia Bulletin, 2011, v. 37 suppl. 1, p. 171

Background: Negative symptoms and neurocognitive deficits in schizophrenia are found to be correlated cross-sectionally but their longitudinal relationship remains unclear. Most studies focused on chronic illness and negative symptoms were examined as single construct instead of its subdomains. We aimed to investigate relationship between diminished expression and neurocognition in patients presenting with first-episode schizophrenia utilizing a prospective design. Methods: Ninety-three subjects (42 males, 51 females, mean age: 31.2) with first-episode schizophrenia, schizoaffective disorder or schizophreniform disorder were followed up for 3 years during which regular assessment in neurocognition and symptoms were conducted. Neurocognitive assessments included Wisconsin Card Sorting Test (WCST), digit span, verbal fluency, visual reproduction and logical memory. Cambridge Neurological Inventory (CNI)and PANSS were administered to evaluate neurological soft signs and clinical symptoms respectively. Severity of Diminished Expression (DE) was sum of item scores in Affect, Behaviour and Speech subscales of High Royds Evaluation of Negativity Scale (Mortimer et al. 1989). Results: Neurocognitive deficits were correlated with severity of DE on a cross-sectional basis. When sex, educational level, DUP, chlorpromazine equivalent, positive symptoms, drug-induced Parkinsonism and depression were controlled, regression analysis showed that at year 1, DE was significantly associated with verbal fluency (R square = .12, P < .01); at year 2, DE was predictive of WCST perseverative error (R square = .12, P < .001), WCST categories completed (R square = .10, P < .001), visual reproduction (R square = .16, P = .01) and CNI-motor coordination (R square = .18, P < .05); at year 3, DE was significantly associated with verbal fluency (R square = .09, P < .05) and forward digit span (R square = .05, P

We report the unusual MR appearance of focal extramedullary haematopoiesis (EMH) of the spleen in a 72-year-old man with thrombocytopenia. Variable MR signal characteristics of EMH, which depend upon the amount of fat and the level of haematopoietic activity, have been described previously. We believe, however, that the delayed central enhancement of EMH on MRI findings was exceptional and has not been reported previously. After pathological investigation and correlation, we believe that the central zone containing hypocellular collagenous bundles may account for this specific enhancement.

G protein-coupled receptors (GPCRs) signal through a limited number of G-protein pathways and play crucial roles in many biological processes. Studies of their in vivo functions have been hampered by the molecular and functional diversity of GPCRs and the paucity of ligands with specific signaling effects. To better compare the effects of activating different G-protein signaling pathways through ligand-induced or constitutive signaling, we developed a new series of RASSLs (receptors activated solely by synthetic ligands) that activate different G-protein signaling pathways. These RASSLs are based on the human 5-HT4b receptor, a GPCR with high constitutive Gs signaling and strong ligand-induced G-protein activation of the Gs and Gs/q pathways. The first receptor in this series, 5-HT4-D100A or Rs1 (RASSL serotonin 1), is not activated by its endogenous agonist, serotonin, but is selectively activated by the small synthetic molecules GR113808, GR125487, and RO110-0235. All agonists potently induced Gs signaling, but only a few (e.g., zacopride) also induced signaling via the Gq pathway. Zacoprideinduced Gq signaling was enhanced by replacing the C-terminus of Rs1 with the C-terminus of the human 5-HT2C receptor. Additional point mutations (D66A and D66N) blocked constitutive Gs signaling and lowered ligand-induced Gq signaling. Replacing the third intracellular loop of Rs1 with that of human 5-HT1A conferred ligand-mediated Gi signaling. This Gi-coupled RASSL, Rs1.3, exhibited no measurable signaling to the Gs or Gq pathway. These findings show that the signaling repertoire of Rs1 can be expanded and controlled by receptor engineering and drug selection. © 2007 Chang et al.

The inorganic crystal scintillator CsI(TI) has been used for low energy neutrino and Dark Matter experiments, where the intrinsic radiopurity is an issue of major importance. Low-background data were taken with a Csl(TI) crystal array at the Kuo-Sheng Reactor Neutrino Laboratory. The pulse shape discrimination capabilities of the crystal, as well as the temporal and spatial correlations of the events, provide powerful means of measuring the intrinsic radiopurity of Cs-137 as well as the U-215, U-238 and Th-232 series. The event selection algorithms are described, with which the decay half-lives of (218)po, (214)po, Rn-220, Po-216 and Po-212 were derived. The measurements of the contamination levels, their concentration gradients with the crystal growth axis, and the uniformity among different crystal samples, are reported. The radiopurity in the U-231 and Th-212 series are comparable to those of the best reported in other crystal scintillators. Significant improvements in measurement sensitivities were achieved, similar to those from dedicated massive liquid scintillator detector. This analysis also provides in situ measurements of the detector performance parameters, such as spatial resolution, quenching factors, and data acquisition dead time. (c) 2005 Elsevier B.V. All rights reserved.

The increase of intracellular Ca2+ concentration is an important mechanism that regulates a variety of physiological processes ranging from exocytosis to gene regulation and cell proliferation [1]. Calcium release from intracellular stores (mainly endoplasmic reticulum, ER) or calcium entry through calcium channels can be used by cells to evoke a higher level of cytosolic Ca2+ concentration. In non-excitable cells, a major pathway for Ca2+ influx is via store-operated Ca2+ channels (also known as capacitative calcium entry) [2]. The concept of Store-operated calcium (SOC) channel was first proposed by James Putney in 1986 [3]. In this model, the depletion of intracellular calcium stores triggers calcium entry across the plasma membrane. In 1992, Hoth & Penner identified the presence of this a Ca2+ release-activated Ca2+ current (CRAC) [4]. Using RNA interference (RNAi)-based approaches, STIM1, an intracellular calcium sensor, was found in 2005 [5, 6]. One year later, Orai1 (CRACM1) was discovered as an essential component of store-operated calcium channel in T cells and mast cells [7, 8]. The role of Ca2+ in cell motility has been known for a long time. There is evicence that Ca2+ influx is more important than Ca2+ release in the migration of fibroblast and breast cancer cells [9, 10].

Background Revascularization rates vary substantially between countries in patients with acute ST-elevation myocardial infarction (STEMI). The impact of early revascularization on clinical outcomes in such patients remains uncertain. The ASSENT-2 fibrinolytic trial provides the opportunity to compare revascularization rates following STEMI in patients across 29 countries, and to explore the relationship between revascularization and clinical outcome. Methods Countries participating in ASSENT-2 were grouped into tertiles according to their in-hospital revascularization rates (39%). Baseline characteristics, medication and procedure use, and clinical outcomes of the 16 949 patients enrolled were compared. Multiple Cox regressions were used to assess the relationship between the tertiles and 30-day mortality, the primary endpoint of the ASSENT-2 trial. Multilevel logistic regression models were developed to validate and further extend the findings from the single-level analyses. Results Patients in highest tertile countries were younger, heavier, and more often diabetic or hypertensive. They were more likely to have had a previous myocardial infarction or revascularization procedure. Time to treatment and hospital length of stay were shorter in the highest tertile, and beta-blocker use was more frequent. Stroke rates were low and similar across termites, with no statistically significant difference in rates of intracranial haemorrhage. Recurrent ischaemia and reinfarction were less common in the highest tertile. Mortality rates at 30 days were tower for countries with the highest revascularization rates (5.1% vs 6.9% vs 6.5% for the lower two tertiles, P < 0.001). At 1 year, mortality remained significantly lower in the highest tertile countries (8.4% vs 10.6% vs 9.9%, P = 0.001). Following adjustment for baseline patient characteristics, Cox regression analysis confirmed an excess of 30-day and 1-year mortality in the lowest and intermediate tertiles compared to the highest tertile. The multilevel analyses validated these findings, and demonstrated that a country’s life expectancy and the hospital volume were inversely related to both 30-day and 1-year mortality. Conclusions The highest rate of in-hospital revascularization following fibrinolytic therapy for acute myocardial infarction in this international study was associated with a reduction in recurrent ischaemia, reinfarction, and improved survival at both 30 days and at 1 year. The optimal rates of revascularization in this setting remain to be determined. (C) 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.

Particle production and correlation functions from Au+Au reactions have been measured as a function of both beam energy (2-10.7AGeV) and impact parameter. These results are used to probe the dynamics of heavy-ion reactions, confront hadronic models over a wide range of conditions and to search for the onset of new phenomena.

A 72-year-old woman presented because of cough with fresh blood for 3 days. She had a history of aortic dissection and underwent aortic arch reconstruction 12 years earlier. On arrival, her vital signs included blood pressure …

Based on the observation of sizeable target-transverse-spin asymmetries in single-hadron and hadron-pair production in Semi-Inclusive measurements of Deep Inelastic Scattering (SIDIS), the chiral-odd transversity quark distribution functions $h_1^q$ are nowadays well established. Several possible channels to access these functions were originally proposed. One candidate is the measurement of the polarisation of $\Lambda$ hyperons produced in SIDIS off transversely polarised nucleons, where the transverse polarisation of the struck quark might be transferred to the final-state hyperon. In this article, we present the COMPASS results on the transversity-induced polarisation of $\Lambda$ and $\bar{\Lambda}$ hyperons produced in SIDIS off transversely polarised protons. Within the experimental uncertainties, no significant deviation from zero was observed. The results are discussed in the context of different models taking into account previous experimental results on $h_1^u$ and $h_1^d$., Comment: 18 pages, 6 figures