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Purpose: We investigated whether twice-daily administration of a bilayer tablet formulation of tramadol (35% immediate-release [IR] and 65% sustained-release) is as effective as four-times-daily IR tramadol capsules for managing cancer pain. Methods: This randomized, double-blind, double-dummy, active-comparator, non-inferiority study enrolled opioid-naïve patients using non-steroidal anti-inflammatory drugs or acetaminophen (paracetamol) to manage cancer pain and self-reported pain (mean value over 3 days ≥ 25 mm on a 100-mm visual analog scale [VAS]). Patients were randomized to either bilayer tablets or IR capsules for 14 days. The starting dose was 100 mg/day and could be escalated to 300 mg/day. The primary endpoint was the change in VAS (averaged over 3 days) for pain at rest from baseline to end of treatment/discontinuation. Results: Overall, 251 patients were randomized. The baseline mean VAS at rest was 47.67 mm (range: 25.6–82.7 mm). In the full analysis set, the adjusted mean change in VAS was − 22.07 and − 19.08 mm in the bilayer tablet (n = 124) and IR capsule (n = 120) groups, respectively. The adjusted mean difference was − 2.99 mm (95% confidence interval [CI] − 7.96 to 1.99 mm). The upper 95% CI was less than the predefined non-inferiority margin of 7.5 mm. Other efficacy outcomes were similar in both groups. Adverse events were reported for 97/126 (77.0%) and 101/125 (80.8%) patients in the bilayer tablet and IR capsule groups, respectively. Conclusion: Twice-daily administration of bilayer tramadol tablets was as effective as four-times-daily administration of IR capsules regarding the improvement in pain VAS, with comparable safety outcomes. Clinical trial registration: JapicCTI-184143/jRCT2080224082 (October 5, 2018). [ABSTRACT FROM AUTHOR]

Poor hand hygiene practice has been linked to an increase in the number of infections among children in urban slums. Hands are considered an intersection for bacterial transmission, but it is unclear whether the handwashing technique affects bacteria elimination. This study inves- tigated the effect of handwashing on the concentration of Escherichia coli (E. coli) and factors related to its reduction among children in an urban slum in Bandung, Indonesia. We observed handwashing and conducted repeated hand swabs before and after handwashing among 137 participants. The mean E. coli concentration on the hands decreased after handwashing, with a higher reduction in E. coli count among students who used soap and had soap contact for more than 10 s during handwashing. Cleaning in-between fingers, using soap, soap con- tact for more than 10 s, and drying hands with a single-use towel were effective factors for reducing E. coli concentration after handwashing (p, 0.05). More than half of the swab samples (59%) tested positive for E. coli after handwashing, indicating that the children’s handwashing technique was not effective in completely removing E. coli from the hands. Moreover, sustained and consistent handwashing practice as a daily behavior in children would maximize the effect. [ABSTRACT FROM AUTHOR]

Objective: Globally, the challenge of handwashing with soap (HWWS) still exists despite the importance of HWWS being shown previously. This study aimed to evaluate faecal contamination on the hands of children and to find factors related to faecal contamination from handwashing techniques, HWWS, knowledge and awareness of water, sanitation, and hygiene (WASH), and a comprehensive WASH index.Methods: The study was conducted at two elementary schools with 169 children in a densely populated area of Bandung, Indonesia. The survey involved handwashing observation using a checklist, hand bacteria sampling and questionnaires.Results: Most children (98.7%) had faecal contamination. Girls had significantly fewer Escherichia coli than boys (P < 0.05). Ability in handwashing techniques, HWWS, and knowledge and awareness of WASH were poor in the lower grades. Escherichia coli counts were negatively correlated with handwashing technique (r = -0.171, P < 0.05), HWWS (r = -0.225, P < 0.01) and the WASH index (r = -0.205, P < 0.05).Conclusions: Proper handwashing technique and HWWS at appropriate times can reduce faecal contamination. Moreover, it is important that both grade-based and gender-based handwashing education be considered in elementary school education. [ABSTRACT FROM AUTHOR]

Launched in 2014, Japan-France collaboration on the ASTRID (Advanced Sodium Technological Reactor for Industrial Demonstration) project is active both in reactor design and in R&D fields. CEA, Framatome, JAEA, MHI and MFBR are in charge of this collaboration. In the design field, Japan-France evaluates core assemblies with interferences on seismic events. The objectives of this collaboration are to determine the core assembly lattice displacements under seismic load in order to demonstrate the safe behavior of the core regarding control rod insertion, structural integrity, and reactivity variation, etc. From this point of view, the object of this study is to verify the seismic evaluation method on core assemblies between Japan and France by comparing the results. Using their evaluation method applied to common the ASTRID core input data, Japan and France will calculate a collision load, a horizontal displacement, and a vertical displacement for core assemblies. As the first step of this work, the comparison of each evaluation (modelling and calculation results) is carried out considering the horizontal seismic excitation and without including the vertical component. The analysis of this benchmark calculation shows a satisfactory agreement between the Japanese and French tools and the figures show a good behavior of the core in horizontal direction under French seismic condition. This paper describes the summary of horizontal seismic analysis comparison and the future analysis plan. [ABSTRACT FROM AUTHOR]

• Genomes of AMR E. coli in fecal sludge and sewage were analyzed. • Clonal complex 10 was prevalent among the isolates. • High-risk clones ST1193 and ST131 were detected. • Combining fecal sludge/sewage surveillance and WGS can be effective in AMR surveillance. The global increase of antimicrobial resistance (AMR) is a major public health concern. An effective AMR surveillance tool is needed to track the emergence and spread of AMR. Wastewater surveillance has been proposed as a resource-efficient tool for monitoring AMR carriage in the community. Here, we performed genomic surveillance of antimicrobial-resistant Escherichia coli obtained from fecal sludge and sewage in Uganda to gain insights into E. coli epidemiology and AMR burden in the underlying population. Selective media containing different antibiotic combinations (cefotaxime, ciprofloxacin, cefotaxime + ciprofloxacin + gentamicin) were used to obtain antimicrobial-resistant E. coli from fecal sludge and sewage. Short-read sequencing was performed for the obtained isolates, and a subset of isolates (selected from predominant sequence types (STs)) was also subjected to long-read sequencing. Genomic analysis of the obtained E. coli isolates (n = 181) revealed the prevalence of clonal complex 10, including ST167 (n = 43), ST10 (n = 28), ST1284 (n = 17), and ST617 (n = 4), in both fecal sludge and sewage, irrespective of antibiotics used for selection. We also detected global high-risk clones ST1193 (n = 10) and ST131 (n = 2 clade A, n = 3 subclade C1-M27, and n = 1 subclade C2). Diverse AMR determinants, including extended-spectrum β-lactamase genes (mostly bla CTX-M-15) and mutations in gyrA and parC , were identified. Analysis of the completed genomes revealed that diverse IncF plasmids and chromosomal integration were the major contributors to the spread of AMR genes in the predominant STs. This study showed that a combination of sewage surveillance (or fecal sludge surveillance) and whole-genome sequencing can be a powerful tool for monitoring AMR carriage in the underlying population. [Display omitted] [ABSTRACT FROM AUTHOR]

Low back pain (LBP) is the most common cause of chronic pain. Numerous clinical scales are available for evaluating pain, but their objective criteria in the management of LBP patients remain unclear. This study aimed to determine an objective cutoff value for a change in the Pain Intensity Numerical Rating Scale (ΔPI-NRS) three months after LBP treatment. Its utility was compared with changes in six commonly used clinical scales in LBP patients: Pain Disability Assessment Scale (PDAS), Pain Self-Efficacy Questionnaire (PSEC), Pain Catastrophizing Scale (PCS), Athens Insomnia Scale (AIS), EuroQoL 5 Dimension (EQ5D), and Locomo 25. We included 161 LBP patients treated in two representative pain management centers. Patients were partitioned into two groups based on patient's global impression of change (PGIC) three months after treatment: satisfied (PGIC = 1, 2) and unsatisfied (3–7). Multivariate logistic regression analysis was performed to explore relevant scales in distinguishing the two groups. We found ΔPI-NRS to be most closely associated with PGIC status regardless of pre-treatment pain intensity, followed by ΔEQ5D, ΔPDAS, ΔPSEC, and ΔPCS. The ΔPI-NRS cutoff value for distinguishing the PGIC status was determined by ROC analysis to be 1.3–1.8 depending on pre-treatment PI-NRS, which was rounded up to ΔPI-NRS = 2 for general use. Spearman's correlation coefficient revealed close relationships between ΔPI-NRS and the six other clinical scales. Therefore, we determined cutoff values of these scales in distinguishing the status of ΔPI-NRS≥2 vs. ΔPI-NRS<2 to be as follows: ΔPDAS, 6.71; ΔPSEC, 6.48; ΔPCS, 6.48; ΔAIS, 1.91; ΔEQ5D, 0.08; and ΔLocomo 25, 9.31. These can be used as definitive indicator of therapeutic outcome in the management of chronic LBP patients. [ABSTRACT FROM AUTHOR]

Diversity and productivity of primary producers are known to be influenced simultaneously by resource availability and resource ratio, but the relative importance of these two factors differed among studies and so far only entire phytoplankton communities were investigated which might ignore specific nutrient requirements and stoichiometric plasticity of different functional groups. We measured nutrient availability (DIN, total N [TN], total P [TP]), nutrient imbalance (TN:TP, DIN:TP, N:Pseston), species richness, and abundance of the whole phytoplankton community, as well as those specific for cyanobacteria, diatoms, and dinoflagellates in Cau Hai lagoon in Vietnam. We determined the correlation among these variables, using structural equation modeling. The models applied to the whole phytoplankton community indicated that the nutrient availability (particularly TP and DIN) drove variation in phytoplankton abundance and richness, and that abundance also depended on species richness. The models applied to different functional groups differed considerably from the entire community and among each other, and only a part of the models was significant. The relationship between nutrient availability (mainly TP) and abundance was driven by cyanobacteria, and the relationship between nutrient imbalance (only with N:Pseston) and species richness was driven by diatoms. Remarkably, the positive relationship between species richness and abundance, as consistently observed for the whole phytoplankton community, was only observed for one of the three functional groups (diatoms), indicating that resource complementarity occurs particularly among species of different functional groups. Our results emphasized that nutrient availability (TP and to a lesser extent DIN) as well as nutrient imbalance (albeit only with N:Pseston as proxy) were driving factors for the phytoplankton community in the Cau Hai lagoon and hence alterations in both of these factors leading to a shift in phytoplankton species composition and productivity. [ABSTRACT FROM AUTHOR]

Infectious disease transmission is frequently mediated by the environment, where people's movements through and interactions with the environment dictate risks of infection and/or illness. Capturing these interactions, and quantifying their importance, offers important insights into effective interventions. In this study, we capture high time-resolution activity data for twenty-five Vietnamese farmers during collection and land application of human excreta for agriculture. Although human excreta use improves productivity, the use increases risks of enteric infections for both farmers and end users. In our study, the activity data are integrated with environmental microbial sampling data into a stochastic-mechanistic simulation of E . coli contamination on hands and E . coli ingested. Results from the study include frequent and variable contact rates for farmers' hands (from 34 to 1344 objects contacted per hour per hand), including highly variable hand-to-mouth contact rates (from 0 to 9 contacts per hour per hand). The frequency of hand-to-mouth contacts was substantially lower than the widely-used frequency previously reported for U.S. Office Workers. Environmental microbial contamination data highlighted ubiquitous E . coli contamination in the environment, including excreta, hands, toilet pit, handheld tools, soils, surfaces, and water. Results from the simulation suggest dynamic changes in E . coli contamination on hands, and wide variation in hand contamination and E . coli ingested amongst the farmers studied. Sensitivity analysis suggests that E . coli contamination on hands and ingested doses are most influenced by contamination of handheld tools, excreta, and the toilet pit as well as by frequency of hand-to-mouth contacts. The study findings are especially relevant given the context: no farmers reported adequate storage time of human excreta, and personal protective mask availability did not prevent hand-to-mouth contacts. Integrating high time-resolution activity data into exposure assessments highlights variation in exposures amongst farmers, and offers greater insight into effective interventions and their potential impacts. [ABSTRACT FROM AUTHOR]

• A novel co-current-flow RPB was developed for ammonia removal of waste leachate. • Gas-liquid film resistance was reduced by RPB to improve the ammonia removal rate. • The ammonia removal rate was improved obviously compared to the normal gravity field. • XGBoost model using small datasets was successfully used for mass transfer prediction. Stripping is widely applied for the removal of ammonia from fresh waste leachate. However, the development of air stripping technology is restricted by the requirements for large-scale equipment and long operation periods. This paper describes a high-gravity technology that improves ammonia stripping from actual fresh waste leachate and a machine learning approach that predicts the stripping performance under different operational parameters. The high-gravity field is implemented in a co-current-flow rotating packed bed in multi-stage cycle series mode. The eXtreme Gradient Boosting algorithm is applied to the experimental data to predict the liquid volumetric mass transfer coefficient (K L a) and removal efficiency (η) for various rotation speeds, numbers of stripping stages, gas flow rates, and liquid flow rates. Ammonia stripping under a high-gravity field achieves η = 82.73% and K L a = 5.551 × 10−4 s−1 at a pH value of 10 and ambient temperature. The results suggest that the eXtreme Gradient Boosting model provides good accuracy and predictive performance, with R2 values of 0.9923 and 0.9783 for K L a and η, respectively. The machine learning models developed in this study are combined with experimental results to provide more comprehensive information on rotating packed bed operations and more accurate predictions of K L a and η. The information mining behind the model is an important reference for the rational design of high-gravity-field-coupled ammonia stripping projects. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the relative potency of direct ischemic preconditioning (DIPC) and remote ischemic preconditioning (RIPC) for protection against ischemic spinal cord injury in rabbits and to explore the mechanisms involved.Methods: In experiment 1, we compared the neurological and histopathological outcomes of DIPC, kidney RIPC, and limb RIPC. The DIPC and kidney RIPC groups received two cycles of 5-min occlusion/15-min reperfusion of the abdominal aorta and left renal artery, respectively. The limb RIPC group received two cycles of 10-min occlusion/10-min reperfusion of the femoral arteries bilaterally. Thirty minutes after the conditioning ischemia, spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. In experiments 2 and 3, we investigated whether pretreatment using a free-radical scavenger, dimethylthiourea (DMTU), an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a mitochondrial ATP-sensitive potassium channel antagonist, 5-hydroxydecanoate (5HD), could attenuate the protective effects of DIPC. In experiment 4, comprehensive analysis of phosphorylated proteins in the spinal cord was performed using a Proteome Profiler Array followed by immunoblotting to elucidate the signal pathway activated by DIPC.Results: In experiment 1, DIPC improved the neurological and histopathological outcomes, whereas kidney and limb RIPC had no protective effects. In experiments 2 and 3, strong protective effects of DIPC were reconfirmed but were not attenuated by DMTU, DPCPX, or 5HD. In experiment 4, DIPC induced phosphorylation of Akt2.Conclusions: DIPC, but not kidney or limb RIPC, protected against ischemic spinal cord injury in rabbits. Akt2 might contribute to this protective effect. [ABSTRACT FROM AUTHOR]

Background: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. Methodology/Principal Findings: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. Conclusions/Significance: This method would enable identification of novel specific substrates for kinases such as Rhokinase with high sensitivity. [ABSTRACT FROM AUTHOR]