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We fabricated terahertz (THz) wave emitters from high-temperature superconductor Bi2Sr2CaCu2O8+δ (Bi2212) single crystals annealed under oxygen gas (O2) flow and nitrogen gas (N2) flow conditions. To better understand the annealing effects of the crystal for the device, we evaluated both device properties and a c-axis lattice constant using x-ray diffraction. Compared to the N2-annealed sample, the O2-annealed sample shows higher critical current in the current–voltage characteristics and no clear emission. In addition, multiple hysteresis loops were observed above 75 K. Based on the x-ray diffraction measurements, it is suggested that the presence of multiple hysteresis loops observed in the I–V characteristics of the O2-annealed sample is caused by the existence of layers that have varying levels of oxygen content along the c-axis direction of the crystal. The formation of these layers is attributed to the deposition process of metallic thin films during the device fabrication procedure. This result indicates that the Bi2212 crystal surface of the O2-annealed sample is more sensitive than that of the N2-annealed one. The information is useful for preparing the Bi2212 crystals for THz-wave emitting devices.

Epimerization/C-alkylation of a seven-membered iminosugar with a broad hexosaminidase inhibition spectrum leads to low micromolar HexAB and NagZ inhibitors.

Introduction Cervical spine (c-spine) injury has a high morbidity and mortality in patients over the age of 65; more than 60% result from falls from standing height (Beedham et al., 2019). The Canadian Cervical Spine Rule (Stiell et al., 2001) deems that there is a high risk of c-spine fracture if any of the following apply: The c-spine cannot be cleared clinically if the patient fits any of the above criteria. Imaging should be considered. As a result of recent clinical experiences Trust Guidelines at Stoke Mandeville Hospital now reflect this evidence (Hadley et al., 2019). Methods Fifty patients over the age of 65 who had a computerised tomography (CT) head scan in the Emergency Department (ED) following a traumatic head injury were randomly selected over a 1 month period. Cases were checked for examination of c-spine and/or CT c-spine. Results of the first cycle of the audit were presented at an ED Education Meeting. Indications for CT c-spine were displayed in poster format around the ED. Following these interventions, a re-audit was carried out using the same methodology. Results In fifty patients aged over 65 attending ED during one month, 16% had a CT c-spine in addition to a CT head. There was documented c-spine examination of 16% of those without CT c-spine on admission. In the re-audit 38% of the fifty patients who had a CT head underwent CT c-spine. In the group that did not have imaging of the c-spine, the proportion with documented cervical spine examination on admission remained the same (16%). Conclusion There was a 137.5% increase in the number of patients aged over 65 who appropriately underwent a CT c-spine as per Trust and National guidelines. Simple interventions (staff education and posters within the ED) were sufficient to significantly alter practice. Current trauma triage is not optimal for older patients who are reviewed by more junior doctors, less likely to be transferred to Major Trauma Centres and more likely to die than younger patients with similar injuries (Major Trauma In Older People 2017 Report). An older person’s trauma team in ED with age-appropriate triage would lead to appropriate imaging in a timely fashion, potentially improving the morbidity and mortality of these vulnerable patients.

ABSTRACT: Thermally induced stress changes in rock lead to creation and reactivation of microcracks with accompanying acoustic emissions (AEs). Therefore, monitoring AEs during cooling (or heating) of rock potentially allows us to determine the rock’s original stress state. This approach would require predicting time-dependent changes in the thermally induced stress and applying an appropriate AE-based failure criterion, so that the in situ stress can be determined by subtracting the induced stress from the failure stress. The goal of this research is to develop a technology to determine the stress state in geothermal reservoirs by cooling the borehole circumference and detecting the onset of microscale rock failure. As the first step to achieve this goal, we examined spatio-temporal evolution of AEs which were thermally induced in Westerly Granite blocks by abrupt local cooling. Four sets of experiments were conducted with different sample and cooling geometry, stress state, and preexisting damage (cracks). The preliminary results indicate that the onset of AE activity can be correlated best to the thermal front propagation in rock samples and to the applied stress. Interestingly, pre-existing microcrack damage in rock had little impact on the AE onset behavior. The conditions that lead to the onset of AE activity and its relation to the ultimate tensile strength of rocks – a parameter which is determined from conventional rock testing – are still poorly understood, which requires further investigation. 1 INTRODUCTION Sustainable development of geothermal energy resources requires detailed knowledge about the in situ stress state in the target rocks. In deep boreholes, stress estimation commonly relies on analysis of wellbore wall failures, break-outs and drilling induced tensile fractures, which develop spontaneously after the well is drilled (e.g. Zoback et al., 2003). Active methods of stress measurement are usually limited to hydraulic methods for estimation of the least principal stress (De Bree and Walters, 1989). Several methods of active stress measurement, capable of constraining the entire stress tensor have been proposed, e.g. overcoring (Worotnicki, 1993), hydraulic tests on preexisting fractures (HTPF) (Cornet, 1983), or sleeve fracturing (Stephansson, 1983). However, each of these methods has their associated technical difficulties or deficiencies which make them unpopular in practical application in deep environments.

ABSTRACT: The ultimate aim of hydraulic fracturing is to have a long and conductive flow path that extends from the wellbore into the formation. The effective fracture length is part of a hydraulically propped fracture which contributes to production. The difficulty in achieving economical production targets from shale reservoirs is at the forefront in many exploration companies. Fracture conductivity loss is related to; proppant embedment under depletion, proppant crushing, damage as a result of fracturing fluid, fines migration and proppant-pack permeability-damage are some of the factors that contribute to production decline after hydraulic fracturing in shale reservoirs. The Caney Shale is a calcareous organic-rich mudrock. Various studies have investigated the effect that clay on shale well productivity, however, there is currently no literature on the Caney shale in relation to horizontal wells; all available literature exists in vertical wells as well as on formations of the Caney that are shallow in comparison to an emerging play which is twice the depth. In this paper we investigate stress-dependent fracture conductivity of proppant-filled fractures and proppant embedment in Caney shale through laboratory and modeling studies. API fracture conductivity tests were conducted using 2% KCl on five locations within the Caney shale that consisted of selecting three brittle(reservoir) zones and two ductile zones. Confining pressures range from 1,000 psi to 12,000 psi at 210°F. Conductivity, permeability as well as embedment were measured during the test. Our experimental results have confirmed that improved fracture conductivity is attributed to; proppant size, the increase in porosity of the proppant pack, closure pressure changes and the reduction in fracture conductivity are a function of many factors such as fracture closure stress. The findings from this study could help the stimulation design by providing new insights into the critical factors that are to be determined to facilitate the choice of proppants as well as fracturing fluids for long term production and recovery from shale reservoirs. 1 INTRODUCTION The development of low permeability formations, like shales, has been aided by hydraulic fracturing of horizontal wells (Radonjic et al., 2020). Hydraulic fracturing fluid is injected at a high pressure to induce tensile fractures that can link to and stimulate natural fractures (Katende et al., 2021a,b). Preserving adequate conductivity in hydraulic fractures over the life of the wells is required for economic production; nevertheless, conserving such conductivity can be difficult in some circumstances, particularly in soft, clay-rich formations (Wang et al., 2021). Proppant particles help to keep the fractures open when the pumping stops and the fracturing fluid returns to the wellbore, producing one or more propped hydraulic fractures of varying length, breadth, and height (Katende et al., 2021a). The proppant pack within the hydraulic fracture boosts well output by providing a greater permeability flowpath for hydrocarbons (Duenckel et al., 2016). Proppant in the fracture is under complicated stress conditions, and the interplay between the rock formation and the proppant pack has a significant impact on proppant-pack permeability (Karazincir et al., 2019). Proppant may be embedded (Katende et al., 2021a) in the rock or crushed into small pieces if the proppant size and strength characteristics are not specified appropriately, resulting in a loss in proppant-pack permeability and fracture aperture, and consequently a fall in well output.

We report the synthesis of seven-membered iminosugars derived from a 3

Objectives For early-stage endometrial cancer, laparoscopic surgery is well established in many countries. In Japan, the procedure is covered by insurance from 2014. Since then, laparoscopic surgeries for gynecological cancers have been performed by not only gynecolo-oncologists but also laparoscopic qualified gynecologists. To review the safety of our cases, this IRB-approved study was performed. Methods Operative cases of endometrial cancer were reviewed retrospectively. Results Out of 94 stage I endometrial cancer cases who underwent laparoscopic surgery, total laparoscopic modified radical hysterectomy + laparoscopic pelvic lymphadenectomy was performed for 22 patients. Median operative duration was 238 minutes, and median blood loss was 100mL. We experienced two cases of obturator nerve complete transection. Both of the surgeons were laparoscopic board certificated. In both cases, right obturator nerve was cut near to the branch of internal iliac vein. Surgical video can be revisited for one patient. The nerve covered with lymphatic tissue was dragged out medially under the internal iliac branch, and cut misinterpreted as a lymphatic trunk. For both, although nerve correction was done during surgery by suturing, rehabilitation was necessary. For open surgery, we have never experienced obturator nerve injury during the pelvic lymphadenectomy in the same period. Conclusions Obturator nerve injury during pelvic surgery is possibly frequent in laparoscopic surgery.

Introduction/Background* Uterine leiomyosarcoma (LMS) is notorious for its poor prognosis. New therapeutics strategy for LMS is mandatory. Kinesin family member4A (KIF4A) is a member of the kinesin4 subfamily and plays an important role in cell division. In recent years, KIF4A is revealed to plays significant roles in some cancers with tumor proliferation. The aim of this study is to investigate the role of KIF4A in LMS. Methodology To identify novel biomarkers of LMS, we performed shotgun proteomics of one normal human uterine smooth muscle cell line (UtSMC) and three LMS cell lines, SK-LMS, SKN and SK-UT1, using isobaric tags for relative and absolute quantitation (iTRAQ). Cell variability was evaluated by MST-8 assay in original LMS cells and KIF4A suppressed cells with siRNA in vitro. For evaluation of proliferation in vivo, we established KIF4A knockdown cell lines using shRNA and injected them subcutaneously to 6weeks ICR nude mice and evaluated changes in tumor size over time. To elucidate the mechanism, we performed cell cycle analysis by fluorescence-activated cell sorting (FACS) and western blotting. Result(s)* A total of 2084 proteins were identified using iTRAQ. KIF4A was identified as a protein with more than twice the expression level of normal smooth muscle cells. By western blotting, all three LMS cell line had expressed KIF4A. KIF4A downregulation significantly suppressed the growth of those cell lines in vitro (-37.2±4.73% in SK-LMS, -87.7±4.02% in SKN and -28.1±3.00% in SK-UT1, p Conclusion* We identified a novel expressed protein, KIF4A, which can be a therapeutic target for uterine leiomyosarcoma.

Introduction/Background* Since advanced endometrial cancer (EC) remains a disease with a poor prognosis, the development of novel therapeutic agents are warranted. Previously, we identified lipolysis-stimulated lipoprotein receptor (LSR) as a highly expressed molecule in ovarian cancer (OC) cells and developed an anti-LSR monoclonal antibody. The antibody significantly suppressed tumor growth in EC as well as OC, however the mechanism is largely unclear, and the function of LSR in cancer cells needs to be elucidated. In this study, we focused on apoptosis and ferroptosis in programmed cell deaths and investigated the function of LSR using in vitro and bioinformatic analysis. Methodology We evaluated LSR expression by immunohistochemistry and analyzed overall survival (OS) and clinicopathological features in 228 EC patients. To investigate the mechanism by which LSR affects the prognosis of EC patients, the pathway enrichment analysis was conducted using published proteomic data of EC. In vitro analyses were performed using two human EC cell lines (HEC1 and HEC116) and the activity of signaling pathways were examined by western blotting. Result(s)* Patients were divided into two groups based on LSR expression; High (strongly stained in ≥25% of the lesion, n=153) and Low (strongly stained in Conclusion* LSR contributes to tumor progression and poor prognosis by regulating apoptotic and ferroptotic signaling pathways in endometrial cancer. LSR may be a novel therapeutic target molecule in EC.

An isolate originally obtained from pond water in Osaka in 1992 and identified as Pythium marsipium, was subsequently classified as Globisporangium marsipium. According to molecular phylogenetic analyses based on the internal transcribed spacer regions of the nuclear ribosomal RNA and mitochondrial cytochrome c oxidase subunit 1 genes, this isolate was shown to represent a new species, described here as G. lacustre sp. nov. In addition, two further new combinations are introduced in Globisporangium as G. camurandrum and G. takayamanum based on their DNA phylogeny.

This paper describes a new modeling framework for microscopic to reservoir-scale simulations of hydraulic fracturing and production. The approach builds upon a fusion of two existing high-performance simulators for reservoir-scale behavior: the GEOS code for hydromechanical evolution during stimulation and the TOUGH+ code for multi-phase flow during production. The reservoir-scale simulations are informed by experimental and modeling studies at the laboratory scale to incorporate important micro-scale mechanical processes and chemical reactions occurring within the fractures, the shale matrix, and at the fracture-fluid interfaces. These processes include, among others, changes in stimulated fracture permeability as a result of proppant behavior rearrangement or embedment, or mineral scale precipitation within pores and microfractures, at µm to cm scales. In our new modeling framework, such micro-scale testing and modeling provides upscaled hydromechanical parameters for the reservoir scale models. We are currently testing the new modeling framework using field data and core samples from the Hydraulic Fracturing Field Test (HFTS), a recent field-based joint research experiment with intense monitoring of hydraulic fracturing and shale production in the Wolfcamp Formation in the Permian Basin (USA). Below, we present our approach coupling the reservoir simulators GEOS and TOUGH+ informed by upscaled parameters from micro-scale experiments and modeling. We provide a brief overview of the HFTS and the available field data, and then discuss the ongoing application of our new workflow to the HFTS data set.

The world’s first quasi-axisymmetric stellarator, CFQS, is now under construction. The CFQS will be dedicated to studies on the interaction between flow and turbulence, and confinement improvement by suppression of turbulence in connection with proof-of-principle experiment of quasi-axisymmetry. In order to conduct this experimental research, a heavy ion beam probe (HIBP) system is planned to be installed and utilized to measure the radial electric field and its fluctuation in a CFQS plasma. In this paper, an orbit calculation for a probe beam is performed to verify feasibility of the HIBP in the CFQS. The required beam energy, possible ion species, and the observable region in a CFQS plasma are investigated. The beam attenuation by a CFQS plasma is also estimated for different beam ion species. If we use 133Cs+ as a primary probe beam, the required beam energy is expected to be 30∼50 keV, which is relatively easy to handle. In this case the beam attenuation, evaluated by the ratio between the injected and detected beam currents, is 10−3∼10−2 in a CFQS plasma with a line-averaged electron density of 19 m−3. For a higher density plasma, usage of 85Rb+ is better in terms of low-beam-attenuation, and a high signal-to-noise ratio. The HIBP in the CFQS will provide a great opportunity to study physics experimentally, related to the radial electric field, poloidal flow, and turbulence suppression.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. © 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

The Japan Atomic Energy Agency (JAEA) started the Research and Development (R&D) to improve nuclear prediction techniques for High Temperature Gas-cooled Reactors (HTGRs). The objectives are to introduce a generalized bias factor method to avoid full mock-up experiment for the first commercial HTGR and to introduce reactor noise analysis to High Temperature Engineering Test Reactor (HTTR) experiment to observe sub-criticality. To achieve the objectives, the reactor core of graphite-moderation system named B7/4”G2/8”p8EUNU+3/8”p38EU(1) was newly composed in the B-rack of Kyoto University Critical Assembly (KUCA). The core is composed of the fuel assembly, driver fuel assembly, graphite reflector, and polyethylene reflector. The fuel assembly is composed of enriched uranium plate, natural uranium plate and graphite plates to realize the average fuel enrichment of HTTR and it’s spectrum. However, driver fuel assembly is necessary to achieve the criticality with the small-sized core. The core plays a role of the reference core of the bias factor method, and the reactor noise was measured to develop the noise analysis scheme. In this study, the overview of the criticality experiments is reported. The reactor configuration with graphite moderation system is rare case in the KUCA experiments, and this experiment is expected to contribute not only for an HTGR development but also for other types of a reactor in the graphite moderation system such as a molten salt reactor development.