Broadening of the Divertor Heat Flux Profile in High Confinement Tokamak Fusion Plasmas with Edge Pedestals Limited by Turbulence in DIII-D.

Multimachine empirical scaling predicts an extremely narrow heat exhaust layer in future high magnetic field tokamaks, producing high power densities that require mitigation. In the experiments presented, the width of this exhaust layer is nearly doubled using actuators to increase turbulent transport in the plasma edge. This is achieved in low collisionality, high confinement edge pedestals with their gradients limited by turbulent transport instead of large-scale, coherent instabilities. The exhaust heat flux profile width and divertor leg diffusive spreading both double as a high frequency band of turbulent fluctuations propagating in the electron diamagnetic direction doubles in amplitude. The results are quantitatively reproduced in electromagnetic XGC particle-in-cell simulations which show the heat flux carried by electrons emerges to broaden the heat flux profile, directly supported by Langmuir probe measurements.

Airway management in children with COVID-19.

The novel coronavirus disease (COVID-19) may result in acute respiratory distress syndrome and respiratory failure, necessitating mechanical respiratory support. Healthcare professionals are exposed to a particularly high risk of contracting the virus while providing resuscitation and respiratory support, which may in turn result in grave consequences and even death. Although COVID-19 has been shown to cause milder disease in children, paediatricians and intensivists who provide care for children must be prepared to provide optimal respiratory support without putting themselves or other medical, nursing, and paramedical staff at undue risk. We propose an airway management approach that is especially relevant in the current COVID-19 pandemic and provides instructions for: (1) Elective intubation for respiratory failure; and (2) Emergency intubation during cardiopulmonary resuscitation. To minimise risk, intubation methods must be kept as straightforward as possible and should include the provision of appropriate personal protection and equipment to healthcare workers. We identify two key considerations: that bag-mask ventilation should be avoided if possible and that bacterial and viral filters should be placed in the respiratory circuit. Our novel approach provides a framework for airway management that could benefit paediatric critical care practitioners who provide care for any children with a novel viral illness, with a focus on infection prevention during high-risk airway management procedures.

When to transfuse your acute care patient? A narrative review of the risk of anemia and red blood cell transfusion based on clinical trial outcomes.

This narrative review critically evaluates the evidence for risk of anemia and red blood cell (RBC) transfusion. For this purpose, it assesses large prospective randomized-controlled trials (RCTs) in medical, surgical, and critical care patient populations in which the impact of specific hemoglobin transfusion thresholds are compared. In these trials, the risks of anemia relative to those of RBC transfusion are assessed. The results of published systematic reviews and meta-analyses are also discussed. Lastly, recommendations for patient blood management and treatment of anemia are explored. The main conclusion of this review emphasizes that the decision to transfuse RBCs is complex and depends on the interaction between multiple factors including the balance between the risk of anemia and the risk of RBC transfusion, existing patient comorbidities, and medical and surgical exposures. The transfusion thresholds recommended by current guidelines vary for medical and surgical patient populations. Guidelines suggesting specific transfusion thresholds for different patient populations should be viewed as a starting point for making an informed decision about RBC transfusion. Alternatives to transfusion (i.e., patient blood management), biomarkers of anemia-induced tissue hypoxia, and transfusion alternatives should continue to be evaluated in large RCTs, with the goal of improving event-free survival in critically ill and perioperative patients.

RéSUMé: Ce compte rendu narratif évalue de façon critique les données probantes concernant le risque de l'anémie et de la transfusion d'érythrocytes. Pour ce faire, nous avons évalué des études randomisées contrôlées (ERC) prospectives de grande envergure réalisées auprès de populations de patients médicaux, chirurgicaux et de soins intensifs dans lesquelles l'impact de seuils spécifiques de transfusion d'hémoglobine est comparé. Dans ces études, les risques de l'anémie sont comparés aux risques de la transfusion d'érythrocytes. Les résultats des comptes rendus systématiques et méta-analyses publiés sont également présentés. Enfin, les recommandations concernant la gestion du sang des patients et le traitement de l'anémie sont explorées. La conclusion principale de ce compte rendu souligne que la décision de transfuser des érythrocytes est complexe et dépend de l'interaction de plusieurs facteurs, notamment de l'équilibre entre le risque de l'anémie et le risque de la transfusion d'érythrocytes, les comorbidités existantes du patient, et les risques médicaux et chirurgicaux. Les seuils de transfusion recommandés par les directives actuelles sont différents pour les populations de patients médicaux et chirurgicaux. Les directives proposant des seuils de transfusion spécifiques en fonction des différentes populations de patients devraient être considérées comme point de départ pour prendre une décision informée concernant la transfusion d'érythrocytes. Les alternatives à la transfusion (c.-à-d. la gestion du sang des patients), les biomarqueurs d'une hypoxie tissulaire induite par l'anémie et les alternatives à la transfusion devraient continuer à être évalués dans des ERC d'envergure, avec pour but l'amélioration de la survie sans complication des patients en état critique et périopératoires.

Low temperature magnetic properties of Nd2Ru2O7.

We present magnetic susceptibility, heat capacity, and neutron diffraction measurements of polycrystalline Nd2Ru2O7 down to 0.4 K. Three anomalies in the magnetic susceptibility measurements at 146, 21 and 1.8 K are associated with an antiferromagnetic ordering of the Ru4+ moments, a weak ferromagnetic signal attributed to a canting of the Ru4+ and Nd3+ moments, and a long-range-ordering of the Nd3+ moments, respectively. The long-range order of the Nd3+ moments was observed in all the measurements, indicating that the ground state of the compound is not a spin glass. The magnetic entropy of Rln2 accumulated up to 5 K, suggests the Nd3+ has a doublet ground state. Lattice distortions accompany the transitions, as revealed by neutron diffraction measurements, and in agreement with earlier synchrotron x-ray studies. The magnetic moment of the Nd3+ ion at 0.4 K is estimated to be 1.54(2)µ B and the magnetic structure is all-in all-out as determined by our neutron diffraction measurements.

Characteristics of CA1 place fields in a complex maze with multiple choice points.

For the sake of rigorous control of task variables, hippocampal place cells have been usually studied in relatively simple environments. To approach the situation of real-life navigation in an urban-like environment, we recorded CA1 place cells while rats performance a memory task in a "Townmaze" with two start locations, three alternate paths in the maze midsection, followed by a two-way choice that determined the trial outcome, access to a goal compartment. Further, to test the ability of place cells to update their spatial representation upon local changes in the environment while maintaining the integrity of the overall spatial map to allow effective navigation, we occasionally introduced barriers in the maze mid-section to force the rat to select a nonpreferred route. The "Townmaze" revealed many new interesting features of CA1 neurons. First, we found neurons with 3-5 fields that appear to represent segments on a single common route through the maze. Second, we found neurons with 3-5 fields similarly aligned along the longitudinal or transverse maze axis. Responses to the barriers were assessed separately near and far from the barriers. Appearance of new fields in response to the barriers took place almost exclusively only locally near the barrier, whereas in-field firing rate changes occurred throughout the maze. Further, field location changes did not correlate with the task performance, whereas firing rate changes did. These findings suggest that in a complex environment with blocked distal views, CA1 neurons code for the environment as sequences of significant nodes but are also capable of extracting and associating common elements across these sequences.

Verification of long wavelength electromagnetic modes with a gyrokinetic-fluid hybrid model in the XGC code.

As an alternative option to kinetic electrons, the gyrokinetic total-f particle-in-cell (PIC) code XGC1 has been extended to the MHD/fluid type electromagnetic regime by combining gyrokinetic PIC ions with massless drift-fluid electrons analogous to Chen and Parker [Phys. Plasmas 8, 441 (2001)]. Two representative long wavelength modes, shear Alfvén waves and resistive tearing modes, are verified in cylindrical and toroidal magnetic field geometries.

Fast Low-to-High Confinement Mode Bifurcation Dynamics in a Tokamak Edge Plasma Gyrokinetic Simulation.

Transport barrier formation and its relation to sheared flows in fluids and plasmas are of fundamental interest in various natural and laboratory observations and of critical importance in achieving an economical energy production in a magnetic fusion device. Here we report the first observation of an edge transport barrier formation event in an electrostatic gyrokinetic simulation carried out in a realistic diverted tokamak edge geometry under strong forcing by a high rate of heat deposition. The results show that turbulent Reynolds-stress-driven sheared E×B flows act in concert with neoclassical orbit loss to quench turbulent transport and form a transport barrier just inside the last closed magnetic flux surface.

Polycystic ovary syndrome with hyperandrogenism as a risk factor for non-obese non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is known to be associated with polycystic ovary syndrome (PCOS). However, most studies investigated the prevalence of NAFLD in obese PCOS patients. AIM: To compare the prevalence of non-obese NAFLD in women with or without PCOS, and to assess an independent association between PCOS and NAFLD in a non-obese Asian cohort. METHODS: This was a case-control study using a prospective PCOS cohort. After subjects with other potential causes of chronic liver disease were excluded, 275 non-obese women with PCOS and 892 non-obese controls were enrolled. NAFLD was determined by hepatic ultrasonography. Main outcomes were the prevalence of NAFLD on hepatic ultrasonography between non-obese women with or without PCOS, and an independent association between non-obese NAFLD and PCOS. RESULTS: Non-obese women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (5.5% vs. 2.8%, P = 0.027). PCOS was associated with non-obese NAFLD (odds ratio: 2.62, 95% confidence intervals: 1.25-5.48) after adjustment for age and body mass index (BMI). In women with PCOS, the level of androgenicity represented by free testosterone or free androgen index was associated with NAFLD after adjustment for age, BMI, lipid profile, insulin resistance or glycaemic status. CONCLUSIONS: Non-obese NAFLD is more prevalent in women with polycystic ovary syndrome than in those without. In non-obese patients with polycystic ovary syndrome, hyperandrogenemia may be an independent risk factor for non-obese NAFLD.

MicroRNA Profile of Granulosa Cells after Ovarian Stimulation Differs According to Maturity of Retrieved Oocytes.

Background: Recent animal studies demonstrated that regulating the microRNA (miRNA) in granulosa cells (GCs) modulates the meiotic competence of oocytes. However, the difference in expression profiles of miRNAs in human GCs according to the maturity of the oocyte still remains to be elucidated. Objective: This observational study investigated whether the miRNA profile of human GCs differs according to the maturity of the retrieved oocyte after controlled ovarian stimulation for in vitro fertilization (IVF). Methods: Ten women who underwent ovarian stimulation cycles with GnRH agonist long protocols were recruited. The follicular fluid (FF) from dominant follicles was individually aspirated at oocyte retrieval. Oocytes were divided into two groups according to oocyte maturity ("mature group" vs. "immature group"). GCs were collected from the FF and miRNA was analyzed using real-time PCR. Results: Mean number of MII oocytes in the mature group was 1.6 ± 0.9 with none in the immature group (p = 0.008). Mean number of MI oocytes was 5.6 ± 2.1 in the mature group and 1.0 ± 0.0 in the immature group (p = 0.008). The total number of retrieved oocytes was 8.8 ± 1.9 in the mature group and 2.0 ± 1.2 in the immature group (p = 0.008). The GCs of the mature group showed a significantly lower expression of hsa-let-7b compared to the GCs of the immature group (p < 0.001). Conclusion: Taken together, the miRNA expression profiles of human GCs obtained from dominant follicles are associated with maturity of the adjacent oocyte and may be useful as a prognosticator of IVF outcome.

Effects of Anesthetic Agent Propofol on Postoperative Sex Hormone Levels.

Introduction: Several studies have found anesthetic agents including propofol in ovarian follicular fluid. However, little is known about the effect of anesthetic agents on ovarian function. We aimed to investigate whether there were differences in the postoperative levels of sex hormones when propofol was used as the anesthetic agent. Methods: A retrospective review was done of 80 patients who underwent ovarian surgery, with 72 infertile women serving as controls. Patients were included in the study if their serum estradiol (E2) and follicle stimulating hormone (FSH) levels were measured during their first postoperative menstrual cycle. Results: Patients were grouped according to the use or non-use of propofol as follows: propofol group (n = 39) and non-propofol group (n = 41). The control group did not undergo surgery. Postoperative E2 levels did not differ between the three groups, but FSH levels were significantly higher in the patients who had undergone surgery compared to controls (p < 0.05). Post-hoc analysis of E2 and FSH levels in the propofol and non-propofol groups did not show any significant differences. Conclusions: The use of propofol did not result in any differences compared to other anesthetic agents in terms of postoperative sex hormone levels after gynecologic surgery. The type of anesthetic agent does not seem to affect the postoperative levels of female sex hormones.

The TGF-ß/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia.

Natural killer (NK) cells are key components of the innate immune system, providing potent antitumor immunity. Here, we show that the tumor growth factor-ß (TGF-ß)/SMAD signaling pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia (ALL). We characterized NK cells in 50 consecutive children with B-ALL at diagnosis, end induction and during maintenance therapy compared with age-matched controls. ALL-NK cells at diagnosis had an inhibitory phenotype associated with impaired function, most notably interferon-γ production and cytotoxicity. By maintenance therapy, these phenotypic and functional abnormalities partially normalized; however, cytotoxicity against autologous blasts remained impaired. We identified ALL-derived TGF-ß1 to be an important mediator of leukemia-induced NK cell dysfunction. The TGF-ß/SMAD signaling pathway was constitutively activated in ALL-NK cells at diagnosis and end induction when compared with healthy controls and patients during maintenance therapy. Culture of ALL blasts with healthy NK cells induced NK dysfunction and an inhibitory phenotype, mediated by activation of the TGF-ß/SMAD signaling pathway, and abrogated by blocking TGF-ß. These data indicate that by regulating the TGF-ß/SMAD pathway, ALL blasts induce changes in NK cells to evade innate immune surveillance, thus highlighting the importance of developing novel therapies to target this inhibitory pathway and restore antileukemic cytotoxicity.

Polymorphisms in period genes and bone response to hormone therapy in postmenopausal Korean women.

OBJECTIVE: In this study, we aimed to explore the association between polymorphisms in the period (PER) gene and bone response to hormone therapy (HT) in postmenopausal Korean women. METHODS: The PER1 c.2284C > G, c.2247C > T, PER2 c.3731G > A, PER3 c.2592G > A, c.3083T > C polymorphisms, and PER3 54bp variable number of tandem repeats (VNTR) were analyzed in 509 postmenopausal Korean women who received HT. Bone mineral density (BMD) at the lumbar spine and femoral neck before and after 1 year of HT and serum levels of osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-κB ligand (sRANKL) and bone turnover markers were measured after 6 months of HT. RESULTS: The PER1 c.2884 C > G polymorphism and PER3 54bp VNTR were associated with annual percent changes in BMD of the femoral neck after 1 year of HT (p < 0.05). Changes in BMD at the femoral neck in the non-CC genotype of the PER1 c.2884C > G polymorphism and in the 4-repeat homozygote of PER3 54bp VNTR were significantly lower than those in CC genotype and non-4-repeat homozygote, respectively. The PER1 c.2884C > G polymorphism was associated with the non-response (>3% BMD loss/year after HT) of HT. The non-CC genotype of the PER1 c.2884C > G polymorphism showed a 1.92-times higher risk of non-response at the lumbar spine and/or femoral neck (p = 0.01) compared with the CC genotype. No significant changes in bone markers after 6 months of HT were noted according to the PER1 c.2884C > G polymorphism. CONCLUSIONS: The PER1 c.2884C > G polymorphism may be associated with risk of non-response to HT in postmenopausal Korean women.

YAP activation protects urothelial cell carcinoma from treatment-induced DNA damage.

Current standard of care for muscle-invasive urothelial cell carcinoma (UCC) is surgery along with perioperative platinum-based chemotherapy. UCC is sensitive to cisplatin-based regimens, but acquired resistance eventually occurs, and a subset of tumors is intrinsically resistant. Thus, there is an unmet need for new therapeutic approaches to target chemotherapy-resistant UCC. Yes-associated protein (YAP) is a transcriptional co-activator that has been associated with bladder cancer progression and cisplatin resistance in ovarian cancer. In contrast, YAP has been shown to induce DNA damage associated apoptosis in non-small cell lung carcinoma. However, no data have been reported on the YAP role in UCC chemo-resistance. Thus, we have investigated the potential dichotomous role of YAP in UCC response to chemotherapy utilizing two patient-derived xenograft models recently established. Constitutive expression and activation of YAP inversely correlated with in vitro and in vivo cisplatin sensitivity. YAP overexpression protected while YAP knockdown sensitized UCC cells to chemotherapy and radiation effects via increased accumulation of DNA damage and apoptosis. Furthermore, pharmacological YAP inhibition with verteporfin inhibited tumor cell proliferation and restored sensitivity to cisplatin. In addition, nuclear YAP expression was associated with poor outcome in UCC patients who received perioperative chemotherapy. In conclusion, these results suggest that YAP activation exerts a protective role and represents a pharmacological target to enhance the anti-tumor effects of DNA damaging modalities in the treatment of UCC.

Engineering of a lipid-polymer nanoarchitectural platform for highly effective combination therapy of doxorubicin and irinotecan.

We developed a highly stable lipid-polymer nanoarchitectural platform for effective combination therapy of doxorubicin and irinotecan in the polyelectrolyte complex nanoparticle core, followed by incorporation of the whole assembly into a lecithin bilayer. It shows great potential for the treatment of a broad range of cancers.

The harmful effects of consumption of repeatedly heated edible oils: a short review.

It has been a regular practice to repeatedly heat the cooking oil and consume it without knowing the harmful effects of such. The procedure to use repeatedly heated cooking oil is aimed to curb the cost of expenses. Heating results is the formation of free reactive oxygen species (ROS) which is responsible for the oxidative stress and damage to various organs in the body. The present review article discusses the harmful events occurring due to consumption of repeated heating of edible oil. A strong message is aimed to generate public awareness of the deleterious effects of consumption of heated edible oil which may help in curbing hypertension and atherosclerosis.

Association between polymorphisms in period genes and bone density in postmenopausal Korean women.

OBJECTIVE: In the present study, we aimed to investigate the association between genetic polymorphisms in period (PER) genes and bone mineral density (BMD) in postmenopausal Korean women. METHODS: The PER1 c.2247C> T and c.2884C> G polymorphisms; the PER2 c.661G> A and c.3731G> A polymorphisms; the PER3 c.2592G> A, c.3029C> T, c.3035C> T, and c.3083T> C polymorphisms, and the 54 bp variable number tandem repeats polymorphism were analyzed in 551 postmenopausal Korean women. Serum leptin, soluble leptin receptor, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, and bone markers including bone alkaline phosphatase and carboxy-terminal telopeptide of type I collagen were measured, and the lumbar spine and femoral neck BMDs were also determined. RESULTS: The PER2 c.661G> A, PER3 c.3029C> T and c.3035C> T polymorphisms were not observed. The PER2 and PER3 polymorphisms evaluated were not related to BMD, whereas associations of the c.2247C> T and c.2884C> G polymorphisms in PER1 with the lumbar spine BMD were observed both singly and in combination. The CC haplotype homozygotes showed significantly lower lumbar spine BMD than participants with other genotypes. Additionally, 2.01-fold higher odds for osteoporosis of the lumbar spine were found in the CC haplotype homozygotes compared to women not carrying the haplotype CC allele. No significant differences in bone markers were detected according to the PER1 haplotype genotype. CONCLUSIONS: Our results suggest that both the PER1 c.2247C> T and c.2884C> G polymorphisms may be genetic factors affecting the lumbar spine BMD in postmenopausal Korean women.

Andrographolide inhibits HMGB1-induced inflammatory responses in human umbilical vein endothelial cells and in murine polymicrobial sepsis.

AIM: Nuclear DNA-binding protein high-mobility group box 1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions, such as septic shock, upregulating pro-inflammatory cytokines. Andrographolide (AG) is isolated from the plant of Andrographis paniculata and used as a folk medicine for treatment of viral infection, diarrhoea, dysentery and fever. However, the effect of AG on HMGB1-induced inflammatory response has not been studied. METHODS: Firstly, we accessed this question by monitoring the effects of post-treatment AG on lipopolysaccharide (LPS) and caecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1-mediated regulation of pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice. RESULTS: Post-treatment AG was found to suppress LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangements. AG also inhibited HMGB1-mediated hyperpermeability and leucocyte migration in septic mice. In addition, AG inhibited production of tumour necrosis factor-α (TNF-α) and activation of AKT, nuclear factor-κB (NF-κB) and extracellular-regulated kinases (ERK) 1/2 by HMGB1 in HUVECs. AG also induced downregulation of CLP-induced release of HMGB1, production of interleukin (IL) 1ß/6/8 and mortality. CONCLUSION: Collectively, these results suggest that AG may be regarded as a candidate therapeutic agent for the treatment of vascular inflammatory diseases via inhibition of the HMGB1 signalling pathway.

Epidemiology and risk factors for severe respiratory syncytial virus infections requiring pediatric intensive care admission in Hong Kong children.

PURPOSE: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infection in young children. However, there are limited data on severe RSV infection requiring pediatric intensive care unit (PICU) admission. This retrospective study described features of RSV-associated PICU admissions in Hong Kong and investigated factors for mortality and duration of PICU stay. METHODS: Children with laboratory-confirmed RSV infection and admitted to the PICUs of all eight government hospitals in Hong Kong between January 2009 and June 2011 were identified from computerized auditing systems and PICU databases. RSV in respiratory samples was detected by direct immunofluorescence and/or viral culture. The relationships between mortality and PICU duration and demographic and clinical factors were analyzed. RESULTS: A total of 118 (2.4 %) PICU admissions were identified among 4,912 RSV-positive pediatric cases in all hospitals. Sixty-five (55.6 %) patients were infants. PICU admissions were higher between October and March. Eight (6.8 %) patients died, but only two were infants. RSV-associated mortality was related to prior sick contact, presence of older siblings, neurodevelopmental conditions, chromosomal and genetic diseases, and bacterial co-infections, but none was significant following logistic regression analyses (odds ratio 9.36, 95 % confidence interval 0.91-96.03 for prior sick contact, p = 0.060). Chronic lung disease was the only risk factor for the duration of PICU admission (ß = 0.218, p = 0.017). CONCLUSIONS: The majority of RSV-infected children do not require PICU support. There is winter seasonality for RSV-associated PICU admission in Hong Kong. Prior sick contact is the only risk factor for RSV-associated mortality, whereas the presence of chronic lung disease is associated with longer PICU stay. The current risk-based approach of RSV prophylaxis may not be effective in reducing severe RSV infections.