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Objective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES.Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided.Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity.Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials. (C) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. Device appraisal showed moderate digitalization readiness, with high safety and the possibility of trial implementation, but low connectivity. Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; although they reached no consensus about aspects regarding methodological biases. We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.Graphical Abstract. Consensus Roadmap(A) Recruitment process. The study procedure started with defining the components of the research problem by the core research team. After defining the problems, two different sets of participants (the steering committee (SC) including key leaders of the field identified by the core team and the expert panel (EP) as a more diverse group of experts identified based on the number of publications based on a systematic review) were identified and were invited to participate in a Delphi study. The study facilitators (first and last authors) led the communications with the SC to design the initial questionnaire through an iterative approach. (B) Evidence synthesis: To collect the available evidence, companies producing portable tES (ptES) devices were contacted, based on the companies suggested by the SC and EP to provide details about the available devices. For mapping methodological processes of digitizing tES trials, two distinct strategies were performed and embedded into the questionnaire, namely SIPOC (Suppliers, Inputs, Process, Outputs, and Customer) and SWOT (Strengths, Weaknesses, Opportunities, and Threats) assessment were performed and embedded into the questionnaire. (C) Consensus development: In the next phase, the questionnaire was validated and finalized via collecting and summarizing opinions. Afterward, the SC and EP responded to the final questionnaire, and results were analyzed providing a list of recommendations for running tES digital trials based on a pre-registered consensus threshold.

The aim of this study was to investigate whether carbohydrate mouth rinse (CMR) improves physical performance of cyclists during a 30-km time trial test and its influence on water balance compared to other strategies of fluid intake. Eleven recreationally trained male cyclists completed a 30 km time trial cycle ergometer under three experimental interventions: (a) CMR, (b) drinking to replace all weight loss (DWL), and (c) drinking “ad libitum” (DAL). Time to complete the 30 km time trial, heart rate, average power, velocity, weight loss, urine color, urine density and pH were evaluated. Statistical analysis was performed using repeated measures analysis of variance (RM-ANOVA) and generalized estimating equations (GEE) with Bonferroni adjustment (p < 0.05). Time to complete the 30 km time trial was similar among CMR 54.5 ± 2.9 min, DWL 53.6 ± 3.9 min and DAL 54.5 ± 2.5 min (p = 0.13). CMR (1.7 ± 0.4%) elicited similar water loss compared to the DAL (1.4 ± 0.6%) intervention, but it was higher than the DWL intervention (0.6 ± 0.6%) (p < 0.01). CMR did not improve the performance of recreationally trained cyclists in a 30 km time trial test compared to other fluid intake strategies. Furthermore, CMR causes higher water loss compared to DWL intervention.

Fatigue failure of steel occurs when small cracks form in a component and then continue to grow to a size large enough to cause failure. In order to understand the strength of steel components, it is important to find the cracks, which eventually grow to cause failures. However, at present, it is not easy to distinguish, in the early stages of growth, the cracks that will grow fast and cause failure. We hypothesized that it may be possible to distinguish them by comparing changes in the magnetic flux density around the tips of those cracks that grew to failure. In order to measure these changes in magnetic flux density, we developed a scanning Hall probe microscope and observed the fatigue cracks growing from artificial slits in soft bearing steels. Note that we did not magnetize the specimens artificially but succeeded to measure the changes in magnetic flux density during the fatigue tests. We also compared the changes in magnetic flux density around crack tips, which grew under different loads, and found that there is a strong correlation between the magnetic flux density, crack growth and stress intensity factors. In order to understand this, we looked into the relation between stress field, residual strain and magnetic flux density, and concluded that the changes in magnetic flux density are caused not only by the residual strain occurring around the crack tips but also by the increase in the elastic stress.

There are many complications of severe acute pancreatitis (SAP), but infected pancreatic necrosis and pancreatic abscess are very serious and relate to the mortality and morbidity. Recently there have been many studies about the utility of procalcitonin (PCT) as a factor of prediction for infective complications in SAP.

When combined with a nonlinear waveguide crystal, Cherenkov phase matching allows for highly effective generation of high power and broadband terahertz (THz) waves. Using a ridged Lithium Niobate (LiNbO3) waveguide coupled with a specially designed silicon lens, we successfully generated THz waves with intensity of approximately three orders of magnitude stronger than those from conventional photoconductive antenna. The broadband spectrum was from 0.1 THz to 7 THz with a maximum dynamic range of 80 dB. The temporal shape of time domain pulse is a regular single cycle which could be used for high depth resolution time of flight tomography. The generated THz wave can also be easily monitored by compact room-temperature THz camera, enabling us to determine the spatial characteristics of the THz propagation.

Patients with constipation may have various pelvic complaints of difficult evacuation coexisting with infrequent evacuation and other abdominal complaints, and the overlapping of symptoms makes it difficult to select appropriate therapy based on clinical history and routine office examination alone. Cinedefecography is an objective method for examining patients who have complex subjective symptoms. This study assessed the value of cinedefecography for evaluating patients with constipation with multiple complaints. We divided 185 patients with constipation into two those with (group 1) or without (group 2) cinedefecographic evidence of difficult evacuation. These groups were compared relative to complaints, manometric results, cinedefecography findings, and the success of biofeedback treatment. Group 1 patients were further evaluated according to the type of abnormal findings: sigmoidocele, rectocele, intussusception, and perineal descent. We found no significant differences in patient complaints between the groups. However, there were more patients in group 2 with intussusception than in group 1; there were also significant differences between the groups in mean resting pressure, maximum resting pressure, and maximum squeeze pressure. In group 1 patients with rectocele complained more frequently of excessive straining, and those with intussusception complained more frequently of incomplete evacuation. Sensory threshold and maximal tolerable capacity were significantly higher in patients with intussusception. Rectocele was predominant in women, and biofeedback treatment was extremely advantageous (86%) for patients in group 1 with a rectocele in association with other pathology. Whether the intussusception or the descent causes decreased mean resting and mean and maximum squeeze pressures is unknown but is an additional and potentially important finding which needs further elucidation for it to have therapeutic significance.

Remotely Operated Vehicles (ROV) are currently in use for visual inspections within reactor pressure vessels (RPV). In boiling water reactors (BWR), there is a complex RPV consisting of structures which are not disassembled during outages. To inspect the large volume of the RPV and associated components, the inspection vehicle must be compact and easily maneuverable. Toshiba has developed an ROV for the purpose of visual inspections in BWRS. This paper describes this ROV, the most compact visual inspection submersible yet manufactured and used in a BWR.

Recently, the electromagnetic damper, which is composed of an electric motor, a ball screw, and a nut, was proposed. The electromagnetic damper has high responsiveness, controllability, and energy saving performance. It has been reported that it improved ride comfort and drivability. In addition, the authors have proposed a coupling method of two electromagnetic dampers. The method enables the characteristics of bouncing and rolling or pitching motion of a vehicle to be tuned independently. In this study, the authors increase the number of coupling of electromagnetic dampers from two to four, and propose a method to couple four electromagnetic dampers. The proposed method enables the characteristics of bouncing, rolling and pitching motion of a vehicle to be tuned independently. Basic experiments using proposed circuit and motors and numerical simulations of an automobile equipped with the proposed coupling electromagnetic damper are carried out. The results indicate the proposed method is effective.

UT-7 is a human leukemic cell line capable of growing in interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), or erythropoietin (Epo) (Komatsu et al, Cancer Res 51:341, 1991). To study the effect of Epo on proliferation and differentiation of UT-7, we maintained the UT-7 cell culture for more than 6 months in the presence of Epo. As a result, a subline, UT-7/Epo, was established. The growth of UT-7/Epo could be supported by Epo but not by GM-CSF or IL-3. UT- 7/Epo showed a greater level of heme content and ratio of benzidine- positive staining cells than did UT-7. Butyric acid promoted the synthesis of hemoglobin in UT-7/Epo, but not UT-7. Further, the mRNA concentrations of the c-myb oncogene and GM-CSF receptor beta-subunit were decreased substantially in UT-7/Epo cells. These findings showed that UT-7/Epo cells had progressed further in erythroid development than UT-7 cells, and suggested that long-term culture in Epo had promoted this differentiation. Whereas availability of the Epo receptor (Epo-R) for binding of Epo was reduced in UT-7/Epo cells compared with UT-7 cells, the Epo-R showed a similar affinity for Epo. This observation suggested that change(s) in postreceptor signaling step might be involved in the establishment and maintenance of the UT-7/Epo phenotype.

Neural RNA-binding proteins are thought to play important roles in neural development and the functional regulation of postmitotic neurones by mediating post-transcriptional gene regulation. RNA-binding proteins belonging to the Musashi family are highly expressed in the nervous system; however, their roles are poorly understood.We identified a Caenorhabditis elegans Musashi homologue, MSI-1, whose RNA-recognition motifs show extensive similarity to those of Drosophila and vertebrate Musashi proteins. We isolated a msi-1 mutant and found males with this mutation to have a mating defect. C. elegans male mating behaviour includes a distinct series of steps: response to contact, backing, turning, vulva location, spicule insertion, and sperm transfer. msi-1 is required for the turning and vulva location steps. Like other Musashi family members, MSI-1 is expressed specifically in neural cells, including male-specific neurones required for turning and vulva location. However, msi-1 was not expressed in proliferating neural progenitors in C. elegans, unlike the Musashi family genes in other systems.Our results suggest that msi-1 is expressed specifically in postmitotic neurones in C. elegans. msi-1 is required for full development of male mating behaviour, possibly through regulation of msi-1 expressing neurones.

We generated a series of knockin mouse lines, in which the cytokine receptor gp130-dependent STAT3 and/or SHP2 signals were disrupted, by replacing the mouse gp130 gene with human gp130 mutant cDNAs. The SHP2 signal-deficient mice (gp130F759/F759 were born normal but displayed splenomegaly and lymphadenopathy and an enhanced acute phase reaction. In contrast, the STAT3 signal-deficient mice (gp130FXQ/FXXQ) died perinatally, like the gp130-deficient mice (gp130D/D). The gp130F759/F759 mice showed prolonged gp130-induced STAT3 activation, indicating a negative regulatory role for SHP2. Th1-type cytokine production and IgG2a and IgG2b production were increased in the gp130F759/F759 mice, while they were decreased in the gp130FXXQ/FXXQ immune system. These results indicate that the balance of positive and negative signals generated through gp130 regulates the immune responses.

Saiko-ka-ryukotsu-borei-to (TJ-12) is a traditional Chinese-Japanese medicinal mixture clinically used for the treatment of hypertension and/or atherosclerosis concurrent with neurotic disorders. Study on the effect of TJ-12 on the vasoconstriction of cutaneous arterioles induced by nor-adrenaline (NA) was carried out using a rabbit ear chamber (REC) under conscious conditions. Before and after oral administration of TJ-12 everyday for 2 weeks, the same position of an arteriole within a REC was analyzed using an image shearing monitor every minute up to 15 min after varying doses (0.3, 1.0, 3.0 and 10.0 micrograms/kg i.v.) of NA. The changes of mean arteriolar diameter and vasomotion amplitude, before and after feeding of TJ-12 (1% w/w) supplemented diet were compared in the same position. Consequently, the pretreatment with TJ-12 significantly attenuated the changes of mean diameter of NA-induced vasoconstriction and also shortened its duration. In addition, concurrent with its cutaneous microcirculatory response, the pretreatment with TJ-12 systemically suppressed the increase of blood pressure under NA-induced vasoconstriction. These results suggest that the anti-pressor effect of TJ-12 might be apparently attributable to the inhibition of NA-induced vasoconstriction.

The subchronic effects of locally applied of static magnetic fields (SMF) on the cutaneous microcirculation within the rabbit ear chamber (REC) were evaluated under conscious conditions. The microcirculatory vasomotion within a REC was measured continuously and analyzed multilaterally by microphotoelectric plethysmography and an image shearing monitor. A SMF, a 180 mT (milli Tesla) cylindlical samarium-cobalt permanent magnet was attached on REC for 24 hours to 4 weeks Exposure to SMF for 1-3 weeks significantly induced long-lasting vasodilation with enhanced vasomotion as compared to control group. Thereafter the active vasomotion of SMF group was depressed and/or returned to initial values and there was no difference between SMF and control groups. The results suggest that the subchronic exposure of SMF can bidirectionally modulate microcirculatory vasomotion in cutaneous tissue.

A new cell line, designated BSMZ, was established from a malignant pleural effusion from a woman with breast cancer. This line has a doubling time of 27 h and has now been cultured for over 120 passages. The large, rounded BSMZ cells grow as both a monolayer and as aggregations in suspension. Intracytoplasmic lumen, a finding consistent with results from cells derived from mammary tissue, was detected on ultrastructural analysis. Injection of BSMZ cells into nude mice resulted in the growth of solid tumors 4 weeks after inoculation. The solid tumor was identical to the original BSMZ cells in microscopic and electron microscopic studies. These cells possess an average of 80 chromosomes. Expression of erbB-2 and c-myc genes was increased by 10-fold, while there was no detectable overexpression of the N-ras and c-myb genes. Southern analysis has revealed amplification of the erbB-2 and c-myc loci. The BSMZ cell line may therefore provide a useful model for the study of human breast cancer and overexpression of the erbB-2 gene.

We investigated the effects of nifedipine on left ventricular diastolic function in 17 asymptomatic or minimally symptomatic patients with hypertrophic cardiomyopathy by simultaneously measuring left ventricular pressure and volume with a catheter-tipped manometer and biplane cineangiography. Studies were performed before and 20 minutes after sublingual administration of nifedipine (20 mg). Heart rates were held constant (79 +/- 12 beats/min, mean +/- SD) by right atrial pacing. Left ventricular volumes and instantaneous rates of left ventricular volume were derived from frame-by-frame (20-msec) analyses of left ventricular biplane angiograms. Left ventricular peak systolic pressure (from 122 +/- 21 to 108 +/- 13 mm Hg, p less than 0.01 vs. control) and mean aortic pressure (from 96 +/- 15 to 87 +/- 11 mm Hg, p less than 0.01) decreased significantly with nifedipine. With afterload reduction, left ventricular ejection fraction (from 0.69 +/- 0.12 to 0.74 +/- 0.08, p less than 0.01) and cardiac output (from 6.4 +/- 2.0 to 7.2 +/- 2.2 l/mm, p less than 0.05) increased significantly. However, there was a slight but significant increase in left ventricular end-diastolic pressure (from 15 +/- 8 to 18 +/- 8 mm Hg, p less than 0.05). Nifedipine did not improve left ventricular relaxation as assessed by the time constants of isovolumic pressure decay (t1/2, from 39.8 +/- 6.6 to 39.4 +/- 7.7 msec, NS; t1/e, from 53.8 +/- 9.0 to 54.4 +/- 10.7 msec, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Toranomon Hospital, Tokyo, Japan.A75year-old male complained of left chest pain caused by left malignant pleurisy on admission. This initial symptoms followed gradually by the syndrome of inappropriate secreti on of ADH during 6 months.Postmortem examination proved the production of ADH like substance by the tissues of the primary tumor.

A simple method of evaluating buried-channel layers in BCCD's, using current-voltage measurement, is presented. This method is based on the assumption of uniform layer doping and depletion approximation. The validity of this evaluation method is demonstrated by agreement between calculated and experimental results.

Two types of virus particles, intracisternal type A and extracellular type C with budding, were detected in the same cells of BF osteosarcoma, its cultured cell lines, and their BFO tumors in CBA mice. The type C particles were approximately 100 microns in diameter. The buoyant density of the virions was 1.16g/ml in sucrose and 1.07 g/ml in Ficoll. A 72S RNA was demonstrated by gel electrophoresis, but no DNA was detected. Reverse transcriptase activity was also demonstrated in detergent-treated virions. Thus, the particles seem to be RNA virus. Cellular transformation and focus formation were observed after rat and mouse embryo cell monolayers were infected with the virus. The same kind of osteosarcoma was produced by inoculation of cloned transformed cells (BFOSV) of CBA embryo cells into CBA mice. Thus, the virus seems to be an oncornavirus.