Non-invasive transcriptomic analysis using mRNAs in skin surface lipids obtained from children with mild-to-moderate atopic dermatitis.

BACKGROUND: Specimens for analysing the molecular pathology of skin disease are generally obtained through invasive methods, such as biopsy. However, less burdensome methods are desirable for paediatric patients. We recently established a method that comprehensively analyses RNA present in sebum (skin surface lipid-RNAs: SSL-RNAs) using a next-generation sequencer. Using this method, biological information can be obtained from the skin in a completely non-invasive manner. OBJECTIVES: To verify the applicability of the SSL-RNA method for analysis of paediatric skin and analyse the molecular pathology of mild-to-moderate atopic dermatitis (AD) in children. METHODS: We collected sebum specimens from the whole faces of 23 healthy children and 16 children with mild-to-moderate AD (eczema area and severity index (EASI) score: 5.9 ± 2.6) ranging in age from 6 months to 5 years, using an oil-blotting film. We then extracted SSL-RNAs from the samples and performed an AmpliSeq transcriptomic analysis. RESULTS: The expressions of genes related to keratinization (LCE, PSORS1C2, IVL and KRT17), triglyceride synthesis and storage (PLIN2, DGAT2 and CIDEA), wax synthesis (FAR2), ceramide synthesis (GBA2, SMPD3 and SPTLC3), antimicrobial peptides (DEFB1) and intercellular adhesion (CDSN), all of which are related to the skin barrier, are lower in children with AD than in healthy children. The children with AD also have higher expression of CCL17, a Th2-cytokine and an increased Th2-immune response as demonstrated by a gene set variation analysis. Moreover, KRT17 and CCL17 expression levels are significantly correlated with the EASI score. CONCLUSIONS: Molecular changes associated with abnormal immune responses and the epidermal barrier in children with mild-to-moderate AD can be determined using the SSL-RNA method. This non-invasive method could therefore be a useful means for understanding the molecular pathology of paediatric AD.

Evaluation of flexible ureteroscope with an omni-directional bending tip, using a JOYSTICK unit (URF-Y0016): an ex-vivo study.

PURPOSE: To compare the range of reach of our newly designed omni-directional ureteroscope (URF-Y0016), compared to the commonly used URF-P6, FlexX2s, and LithoVue™ scopes, in the upper, middle, and lower calyces in an ex-vivo pyelocaliceal model. METHODS: We fabricated a three-dimensional pyelocaliceal model of the upper, middle, and lower pole calyces using urethane and acrylic resin. The inner surface of the dome of each calyx was engraved with reference lines along eight directions, set at 10° of latitude from the top to the base of the dome, and at angles of 0-90°, to precisely determine the range of reach of each scope. The main feature of the URF-Y0016 scope is the omni-directional bending of the tip of the flexible ureteroscope, with the control of these four directions integrated into a handgun-type control unit with a joystick. The range of reach within each calyx was measured by four expert surgeons. RESULTS: The URF-Y0016 scope provided a greater range of reach along all directions in the lower pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p < 0.001), particularly along the anterior-posterior direction in the lower lobe calyx. However, the URF-Y0016 scope did not influence the improvement of reach range in the upper and middle pole calyx compared to URF-P6, FlexX2s, and LithoVue™ scopes (p = 0.08, p = 0.296). CONCLUSION: The novel design of the URF-Y0016 could improve treatment outcomes for calyceal stones in the lower pole in practice.

Heat-killed Lactobacillus brevis KB290 attenuates visceral fat accumulation induced by high-fat diet in mice.

AIMS: This study aimed to evaluate the anti-adiposity effect of heat-killed Lactobacillus brevis KB290 originating from traditional Japanese fermented pickles in mice fed a high-fat diet (HFD). METHODS AND RESULTS: C57BL/6J mice were fed a normal-fat diet, HFD or HFD supplemented with heat-killed KB290 for 8 weeks. Epididymal and renal adipose tissue weights, as well as areas of epididymal adipocytes, were significantly lower in the mice fed a HFD supplemented with KB290 than in those fed an unsupplemented HFD. Mice whose diets were supplemented with KB290 had elevated adiponectin and ß3-adrenergic receptor expression in epididymal adipose tissue and an accompanying higher serum free fatty acid level. Furthermore, the HFD-induced elevations in serum glucose, insulin and HOMA-IR were significantly suppressed by dietary supplementation with KB290. Amplicon sequencing of 16S rRNA genes revealed that KB290 ingestion altered the composition of the intestinal microbiota. CONCLUSIONS: Heat-killed L. brevis KB290 suppressed diet-induced visceral fat accumulation and ameliorated diet-induced metabolic symptoms and intestinal gut microbiota modifications, suggesting possibility of novel paraprobiotic. SIGNIFICANCE AND IMPACT OF THE STUDY: Heat-killed L. brevis KB290 is useable as a material to develop functional foods that attenuate visceral fat accumulation.

Sodium and salt content of Portuguese rolls produced in a city of southern Brazil: a comparison of laboratory analysis, food labelling and nutrition standards.

OBJECTIVE: To analyse the Na content of bread by comparing the amount of salt and Na among the label, laboratory analysis and international guidelines. DESIGN: Ten selected bakeries provided 3239 randomly selected samples of bread, which were weighed on-site. Triplicate samples were retrieved from each bakery (thirty samples) for analysis. Bread production was observed, and ingredient labels were queried to determine salt weights, which were used for comparison with the laboratory analysis. Flame photometry and the method for chlorides were utilised for analysing Na. Laboratory findings were compared to nine different international nutritional guidelines for Na consumption. SETTING: Florianopolis, south of Brazil. PARTICIPANTS: Ninety independent bakeries locally producing Portuguese rolls were queried; rolls from ten conveniently selected bakeries were retrieved for further analysis. RESULTS: The average weight of the rolls was 50·2 ± 5·3 g. The average amount of salt (g) per roll, by laboratory and label analyses, was 0·69 ± 0·0 and 0·62 ± 0·1 g, respectively. The mean level of Na (mg) reported on nutrient labels (478·2 ± 93·4/100 g) was significantly lower than by laboratory analysis (618·2 ± 73·8/100 g), P < 0·001. There was a difference for Na in rolls produced in the bakeries considering the unit weight of rolls (P ≤ 0·001) per 100 g (P = 0·026) and the mode of production. The consumption of two averaged units of rolls was equivalent to 51·7 % of the Brazilian guideline daily amount for Na for children and 31 % for adults. CONCLUSIONS: The nutrient labels underreported Na values. This study strengthens the importance of monitoring Na of breads in Brazil.

Design of photonic-crystal surface-emitting lasers with enhanced in-plane optical feedback for high-speed operation.

Photonic-crystal surface-emitting lasers (PCSELs) use the two-dimensional (2D) resonance at the band-edge of a photonic crystal for lasing, and they feature various outstanding functionalities such as high-brightness lasing, arbitrary shaping of beam patterns and on-chip 2D beam steering. In this paper, to investigate the applicability of PCSELs for high-speed operation, we design PCSELs with enhanced in-plane optical feedback, which enable single-mode lasing inside a circular region the diameter of which is less than 10 µm. To realize a strong in-plane confinement of the lasing mode, we increase the one-dimensional coupling coefficients between counter-propagating waves through the careful design of the lattice points. We also introduce an in-plane heterostructure composed of two photonic crystals with different photonic bandgaps and utilize reflection at the boundary of the two photonic crystals in addition to the optical feedback at the band-edge of each photonic crystal. By using three-dimensional finite-difference time-domain method (3D-FDTD), we confirm that the proposed hetero-PCSELs can achieve single-mode lasing operation inside a 9-µm-diameter and possibly realize a 3-dB modulation bandwidth larger than 40 GHz.

Validation of the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities.

BACKGROUND: Dementia in people with intellectual disabilities (IDs) is difficult to detect because of preexisting cognitive deficits. An effective screening method is required. The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) was developed as an observer rating tool to screen dementia in people with ID. The aim of this study was to verify the screening accuracy of the DSQIID for Japanese people with ID. METHODS: Four-hundred ninety-three subjects with ID participated in this study. Caregivers who had observed the participants for more than 2 years scored the Japanese version of the DSQIID (DSQIID-J) of the participants. Three doctors examined participants directly and diagnosed dementia using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. To identify the key screening items that predict dementia, the specificities of a single and pairs of items with 100% sensitivity were evaluated relative to the dementia diagnosis. RESULTS: Of 493 participants, 34 were people with Down syndrome (DS), and 459 were people without DS. Seventeen participants were diagnosed with dementia. The suitable cut-off score of the DSQIID-J was 10/11 (sensitivity 100% and specificity 96.8%) for screening dementia. The inter-rater reliability, test-retest reliability and internal consistency of the DSQIID-J were excellent. Regarding key items, there was no single item with 100% sensitivity, and the best two-item combination was the pair of 'Cannot dress without help' and 'Walks slower' (sensitivity 100% and specificity 93.5%). CONCLUSIONS: We identified several important question items of the DSQIID-J related to the diagnosis of dementia in people with ID. The DSQIID-J is a useful screening tool for dementia in adults with ID.

Laser-Beam-Patterned Topological Insulating States on Thin Semiconducting MoS_{2}.

Identifying the two-dimensional (2D) topological insulating (TI) state in new materials and its control are crucial aspects towards the development of voltage-controlled spintronic devices with low-power dissipation. Members of the 2D transition metal dichalcogenides have been recently predicted and experimentally reported as a new class of 2D TI materials, but in most cases edge conduction seems fragile and limited to the monolayer phase fabricated on specified substrates. Here, we realize the controlled patterning of the 1T^{'} phase embedded into the 2H phase of thin semiconducting molybdenum-disulfide by laser beam irradiation. Integer fractions of the quantum of resistance, the dependence on laser-irradiation conditions, magnetic field, and temperature, as well as the bulk gap observation by scanning tunneling spectroscopy and theoretical calculations indicate the presence of the quantum spin Hall phase in our patterned 1T^{'} phases.

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

Thermal behavior, structure, dynamic properties of aqueous glycine solutions confined in mesoporous silica MCM-41 investigated by x-ray diffraction and quasi-elastic neutron scattering.

Differential scanning calorimetry, X-ray diffraction, and quasi-elastic neutron scattering (QENS) measurements of aqueous glycine solutions confined in mesoporous silica (MCM-41) were performed at different glycine concentrations, pH, and loading ratio (=mass of glycine solution/mass of dry MCM-41) in the temperature range from 305 to 180 K to discuss the confinement effect on the thermal behavior, the structure, and the dynamic properties of the solutions. The freezing points of the confined glycine solutions decreased, compared with those of the bulk solutions. The corresponding exothermic peak due to ice formation became broader with an increase in the glycine concentration. By subtracting X-ray diffraction patterns of dry MCM-41 from those of glycine solution-loaded MCM-41, information about the structure of the confined glycine solutions was obtained. The radial distribution functions of the confined glycine solutions showed that the peaks assigned to the interaction between glycine molecules and the surface silanol (Si-OH) groups of MCM-41 at pH = 5 were observed, in contrast to the case at pH = 2. The QENS data on H/D substituted aqueous glycine solutions gave the translational diffusion coefficients and the residence time of glycine and water molecules confined in MCM-41 individually. The activation energy of the diffusion coefficient of a glycine molecule at pH = 5 was larger than that at pH = 2. These results imply that glycine molecules locate near the pore surface of MCM-41 due to the formation of hydrogen bonding between glycine molecules and the silanol group of the MCM-41 wall at pH = 5.

Response of epithelial cells infected by Treponema denticola.

OBJECTIVE: In the gingival crevice, the interaction between epithelial cells and periodontopathic bacteria is important for the development of periodontitis. Treponema denticola is a major pathogen of chronic periodontitis and possesses several virulence factors, such as major surface protein (Msp) and prolyl-phenylalanine-specific protease (dentilisin). Here, we investigated the behaviours of epithelial cells infected with T. denticola by measuring the expression of interleukin (IL)-1ß, IL-6, ß defensin 2 (BD-2) and heat-shock protein 70 (HSP70). METHODS: Epithelial cells were infected with T. denticola wild-type strain, Msp-deficient mutant or dentilisin-deficient mutant, and the expression levels of the above targets were analysed by polymerase chain reaction. RESULTS: Infection with T. denticola wild-type strain and mutants induced the production of IL-6 and HSP70. The level of BD-2 induced by T. denticola wild-type strain at 24 hr was significantly higher than that of the dentilisin-deficient mutant. The level of IL-1ß mRNA in the wild-type strain and dentilisin-deficient mutant was slightly lower than that in the uninfected control. CONCLUSION: These results suggest that the levels of BD-2 were affected by Msp and dentilisin. This effect may contribute to the disruption of the response of epithelial cells to eradicate T. denticola.

Selective release of miRNAs via extracellular vesicles is associated with house-dust mite allergen-induced airway inflammation.

BACKGROUND: MicroRNAs (miRNAs) may facilitate cell-to-cell communication via extracellular vesicles (EVs). The biological roles of miRNAs in EVs on allergic airway inflammation are unclear. METHODS: Airway-secreted EVs (AEVs) were isolated from bronchoalveolar lavage fluid (BALF) of control and house-dust mite (HDM) allergen-exposed HDM-sensitized mice. The expression of miRNAs in AEVs or miRNAs and mRNAs in lung tissue was analysed using miRNA microarray. RESULTS: The amount of AEV increased 8.9-fold in BALF from HDM-exposed mice compared with that from sham-control mice. HDM exposure resulted in significant changes in the expression of 139 miRNAs in EVs and 175 miRNAs in lung tissues, with 54 miRNAs being common in both samples. Expression changes of these 54 miRNAs between miRNAs in AEVs and lung tissues after HDM exposure were inversely correlated. Computational analysis revealed that 31 genes, including IL-13 and IL-5Ra, are putative targets of the miRNAs up-regulated in AEVs but down-regulated in lung tissues after HDM exposure. The amount of AEV in BALF after HDM exposure was diminished by treatment with the sphingomyelinase inhibitor GW4869. The treatment with GW4869 also decreased Th2 cytokines and eosinophil counts in BALFs and reduced eosinophil accumulation in airway walls and mucosa. CONCLUSION: These results indicate that selective sorting of miRNA including Th2 inhibitory miRNAs into AEVs and increase release to the airway after HDM exposure would be involved in the pathogenesis of allergic airway inflammation.

Morphology dependence of the thermal transport properties of single-walled carbon nanotube thin films.

The thermal transport properties of random network, single-walled carbon nanotube (SWNT) films were assessed using Raman spectroscopy. Two types of SWNT films were investigated: single-layer and stacked. The single-layer films were fabricated by aerosol chemical vapour deposition and subsequent direct dry deposition, while the stacked films were prepared by placing the single-layer films on top of one another. The anisotropy of the network structures of each of these films was evaluated based on the angular dependence of the optical absorbance spectra. The results show that the anisotropy of the films decreases with increasing film thickness in the case of the single-layer films, and that the film anisotropy is preserved during the stacking process. The sheet thermal conductance is proportional to the SWNT area density in the case of stacked films, but is reduced with increasing thickness in the case of single-layer films. This effect is explained by a change in the network morphology from a two-dimensional anisotropic structure to the more isotropic structure. This work demonstrates the fabrication of low-density films with high sheet thermal conductance through the stacking of thin SWNT films.

Analysis of morphological changes after facial massage by a novel approach using three-dimensional computed tomography.

BACKGROUND/PURPOSE: Photograph-based visual scoring has been used for evaluation of facial morphological changes. Here, we describe a three-dimensional computed tomography (3D-CT) method for objective analysis of facial and intra-facial (subcutaneous) changes. The effects of facial massage were examined using both methods. METHODS: Subjects were 12 healthy female volunteers without facial scars or deformation (age 30-54 years, mean 39.4 years). Photograph-based scoring of massage-induced morphological changes was done at the nasolabial folds, upper, lower and lateral cheeks and lower eyelids. For 3D-CT evaluation, the virtual center axis (VCA) was set as the cranio-caudal longitudinal line, and the VCA-skin surface distances (VSDs) were measured. Massage-induced changes of VSD were calculated (facial massage-induced change rate, FMCR). Intra-facial (subcutaneous) changes were also evaluated. RESULTS: Photograph-based scoring revealed marked morphological changes of the nasolabial folds after facial massage, and changes of the lower, upper and lateral cheeks and lower eyelid were also observed in more than half of the subjects. FMCR values were significantly changed in the paranasal area, nasolabial fold area and cranial part of the mandibular area. Photograph-based scores at the lower cheek and lower eyelid were well correlated with FMCR in the inferior part of the nasolabial fold and the mandibular area, respectively. Massage-induced changes of subcutaneous fat tissues and facial expression muscles were also apparent on CT images. CONCLUSION: 3D-CT imaging is useful for objective evaluation of the effects of facial massage, including anatomical changes in subcutaneous structures.

Surgical strategy of esophageal resection and reconstruction for aortoesophageal fistula.

Aortoesophageal fistula is a critical and life-threatening disease. The cardiovascular strategy for graft replacement has been widely discussed. However, the surgical strategy of esophageal resection and reconstruction for aortoesophageal fistula has rarely been discussed. The objective of this study is to establish a surgical strategy and procedure of esophageal resection and reconstruction for aortoesophageal fistula. Eleven patients with aortoesophageal fistula who underwent aortic graft replacement and esophagectomy between 2008 and 2015 at Kobe University Hospital were enrolled in this study. Patient characteristics, operative methods, and clinical outcomes were obtained by retrospective chart review. All 11 patients underwent graft replacement, esophagectomy, and omental wrapping. Ten esophagectomies were simultaneously accomplished in the same operative field as aortic graft replacement. Seven patients underwent subtotal esophagectomy from a left thoracotomy, and three patients underwent upper hemiesophagectomy from a median sternotomy. The other patient underwent staged esophagectomy from a right thoracotomy. Seven of 11 patients (63.6%) successfully underwent staged esophageal reconstruction. Pedicled jejunal transfer with supercharge and superdrainage were performed in six patients, and ileocecal reconstruction was performed in one patient. Median survival time in the patients with esophageal reconstruction was 21 months while that in the patients without esophageal reconstruction was 10 months. Six of 7 patients (85.7%) who underwent esophageal reconstructions were alive. Our surgical strategy for aortoesophageal fistula, which includes simultaneous graft replacement and esophagectomy in the same operative field and staged reconstruction by pedicled jejunal transfer to ensure omental wrapping, is feasible and promising.

Bilateral effects of hospital patient-safety procedures on nurses' job satisfaction.

AIM: The aim of this study was to examine how hospital patient-safety procedures affect the job satisfaction of hospital nurses. Additionally, we investigated the association between perceived autonomy and hospital patient-safety procedures and job satisfaction. BACKGROUND: Recently, measures for patient safety have been recognized as an essential requirement in hospitals. Hospital patient-safety procedures may enhance the job satisfaction of nurses by improving the quality of their work. However, such procedures may also decrease their job satisfaction by imposing excessive stress on nurses because they cannot make mistakes. METHODS: The participants included 537 nurses at 10 private hospitals in Japan (The surveys were collected from March to July 2012). Factors related to hospital patient-safety procedures were demonstrated using factor analysis, and the associations between these factors and nurses' self-perceived autonomy and job satisfaction were examined using structural equation modelling. FINDINGS: Five factors regarding hospital patient-safety procedures were extracted. Additionally, structural equation modelling revealed statistically significant associations between these factors and the nurses' self-perceived autonomy and job satisfaction. The findings showed that nurses' perceived autonomy of the workplace enhanced their job satisfaction and that their perceptions of hospital patient-safety procedures promoted their job satisfaction. However, some styles of chief nurses' leadership regarding patient safety restrict nurses' independent and autonomous decision-making and actions, resulting in a lowering of job satisfaction. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study demonstrated that hospital patient-safety procedures have ambiguous effects on nurses' job satisfaction. In particular, chief nurses' leadership relating to patient safety can have a positive or negative effect on nurses' job satisfaction. The findings indicated that hospital managers should demonstrate positive attitudes to improve patient safety for nurses' job satisfaction. In addition, policymakers in the hospitals should consider that chief nurses' leadership styles may reduce autonomy and suppress nurses' job satisfaction.

Laser frequency locking with 46 GHz offset using an electro-optic modulator for magneto-optical trapping of francium atoms.

We demonstrate frequency offset locking between two laser sources using a waveguide-type electro-optic modulator (EOM) with 10th-order sidebands for magneto-optical trapping of Fr atoms. The frequency locking error signal was successfully obtained by performing delayed self-homodyne detection of the beat signal between the repumping frequency and the 10th-order sideband component of the trapping light. Sweeping the trapping-light and repumping-light frequencies with keeping its frequency difference of 46 GHz was confirmed over 1 GHz by monitoring the Doppler absorption profile of I2. This technique enables us to search for a resonance frequency of magneto-optical trapping of Fr.

Long-term nitrogen compound removal trends of a hybrid subsurface constructed wetland treating milking parlor wastewater throughout its 7 years of operation.

This study evaluated the nitrogen compound removal efficiency of a hybrid subsurface constructed wetland, which began treating milking parlor wastewater in Hokkaido, northern Japan, in 2006. The wetland's overall removal rates of total nitrogen (TN) and ammonium (NH4(+)-N) improved after the second year of operation, and its rate of organic nitrogen (Org-N) removal was stable at 90% efficiency. Only nitrate (NO3(-)-N) levels were increased following the treatment. Despite increased NO3(-)-N (maximum of 3 mg-N/L) levels, TN removal rates were only slightly affected. Removal rates of TN and Org-N were highest in the first vertical bed. NH4(+)-N removal rates were highest in the second vertical bed, presumably due to water recirculation and pH adjustment. Concentrations of NO3(-)-N appeared when total carbon (TC) levels were low, which suggests that low TC prevented complete denitrification in the second vertical bed and the final horizontal bed. In practice, the beds removed more nitrogen than the amount theoretically removed by denitrification, as calculated by the amount of carbon removed from the system. This carbon-nitrogen imbalance may be due to other nitrogen transformation mechanisms, which require less carbon.

Performance of hybrid subsurface constructed wetland system for piggery wastewater treatment.

The objective of this study was to evaluate performance of a hybrid constructed wetland (CW) built for high organic content piggery wastewater treatment in a cold region. The system consists of four vertical and one horizontal flow subsurface CWs. The wetland was built in 2009 and water quality was monitored from the outset. Average purification efficiency of this system was 95±5, 91±7, 89±8, 70±10, 84±15, 90±6, 99±2, and 93±16% for biochemical oxygen demand (BOD5), chemical oxygen demand (COD), total carbon (TC), total nitrogen (TN), ammonium-N (NH4-N), total phosphorus (TP), total coliform (T. Coliform), and suspended solids (SS), respectively during August 2010-December 2013. Pollutant removal rate was 15±18 g m(-2) d(-1), 49±52 g m(-2) d(-1), 6±4 g m(-2) d(-1), 7±5 g m(-2) d(-1), and 1±1 g m(-2) d(-1) for BOD5, COD, TN, NH4-N, and TP, respectively. The removal efficiency of BOD5, COD, NH4-N, and SS improved yearly since the start of operation. With respect to removal of TN and TP, efficiency improved in the first three years but slightly declined in the fourth year. The system performed well during both warm and cold periods, but was more efficient in the warm period. The nitrate increase may be attributed to a low C/N ratio, due to limited availability of carbon required for denitrification.

Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial.

BACKGROUND: Giant cell tumor of bone (GCTB) is a rare primary bone tumor, characterized by osteoclast-like giant cells that express receptor activator of nuclear factor-kappa B (RANK), and stromal cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. A RANKL-specific inhibitor, denosumab, was predicted to reduce osteolysis and control disease progression in patients with GCTB. PATIENTS AND METHODS: Seventeen patients with GCTB were enrolled. Patients were treated with denosumab at 120 mg every 4 weeks, with a loading dose of 120 mg on days 8 and 15. To evaluate efficacy, objective tumor response was evaluated prospectively by an independent imaging facility on the basis of prespecified criteria. RESULTS: The proportion of patients with an objective tumor response was 88% based on best response using any tumor response criteria. The proportion of patients with an objective tumor response using individual response criteria was 35% based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, 82% based on the modified European Organization for Research and Treatment of Cancer (EORTC) criteria, and 71% based on inverse Choi criteria. The median time of study treatment was 13.1 months. CONCLUSION: The findings demonstrate that denosumab has robust clinical efficacy in the treatment of GCTB.