Highest fusion performance without harmful edge energy bursts in tokamak.

The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.

Potential overestimation of cognitive impairment because of hearing loss: impact of test modalities on cognitive test scores.

OBJECTIVE: Hearing impairment in older adults may affect cognitive function and increase the risk of dementia. Most cognitive tests are delivered auditorily, and individuals with hearing loss may fail to hear verbal instructions. Greater listening difficulty and fatigue in acoustic conditions may impact test performance. This study aimed to examine the effect of decreased audibility on cognitive screening test performance in older adults. METHOD: Older adults (n = 63) with different levels of hearing loss completed a standard auditory Mini-Mental State Examination test and a written version of the test. RESULTS: Individuals with moderate to moderately severe hearing loss (41-70 dB) performed significantly better on the written (24.34 ± 4.90) than on the standard test (22.55 ± 6.25), whereas scores were not impacted for mild hearing loss (less than 40 dB). CONCLUSION: Hearing evaluations should be included in cognitive assessment, and test performance should be carefully interpreted in individuals with hearing loss to avoid overestimating cognitive decline.

A survey of enteric organisms detected by real-time PCR assay in faeces of dogs in Western Australia.

This retrospective observational study reports the enteric organisms detected in dogs in Western Australia that had a faecal PCR (fPCR) submitted to a commercial veterinary laboratory. Of 2025 fPCR results, Clostridium perfringens alpha toxin gene was most frequently detected (87.2%), followed by Campylobacter spp. (37.8%), canine parvovirus (10.5%), Giardia spp. (9.7%), Salmonella spp. (7.0%), canine enteric coronavirus (2.3%), and canine distemper virus (0.3%). C.perfringens alpha toxin gene and Campylobacter spp. were the most common organisms co-detected. There was no statistically significant seasonal variation. Further studies are required to elucidate the role these organisms play in gastrointestinal disease in dogs.

Faecal PCR panel results and clinical findings in Western Australian dogs with diarrhoea.

AIM: To describe faecal PCR (fPCR) results and clinical findings of dogs seen at a university teaching hospital for diarrhoea. DESIGN: Retrospective case series (April 2015 to July 2018). PROCEDURE: Data were collected from the hospital electronic medical records. Data extracted included signalment, history, clinical signs, treatment, fPCR panel results, other faecal diagnostic test results and antimicrobial use. RESULTS: One hundred and sixty-eight dogs with diarrhoea had a fPCR panel submitted. Most dogs (115, 68.5%) had diarrhoea of 3 days or less duration. Clostridium perfringens alpha toxin gene was most frequently detected (156, 92.9%) by fPCR, followed by Campylobacter spp. (55, 32.7%), canine parvovirus (CPV) (29, 17.3%), Salmonella spp. (14, 8.3%) and Giardia spp. (9, 5.4%). For the 45 dogs that had a negative point-of-care CPV test, 13 were CPV fPCR positive; some of which were adult dogs with current vaccination status. A total of 94/168 (56%) dogs received antimicrobials at some time during the treatment of diarrhoea. CONCLUSION: Faecal PCR panels can identify dogs with enteric organisms in their faeces that traditional faecal diagnostics may miss, thus contributing additional information to the diagnostic process. Nonetheless, fPCR results should be interpreted in light of the clinical findings, and particular consideration given to avoiding inappropriate use of antimicrobials. This study highlights that testing for C. perfringens alpha toxin gene is not likely to be diagnostically helpful, and that adult dogs with diarrhoea might be identified as CPV positive with PCR testing, despite a negative point-of-care CPV test result and a current vaccination status.

Lipid profile in patients with androgenetic alopecia: a meta-analysis.

BACKGROUND: Many studies have reported that androgenetic alopecia (AGA) might be a risk factor for cardiovascular disorders, and the association of AGA with dyslipidaemia has been studied. However, the results were controversial and previous meta-analyses had several critical limitations. OBJECTIVE: We performed a meta-analysis to clarify whether AGA patients have abnormal lipid profiles. METHODS: A literature search was performed using the MEDLINE, EMBASE, The Cochrane Library and KOREA MED databases. RESULTS: We pooled 19 observational studies and performed a meta-analysis to compare serum total cholesterol, serum triglyceride (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) and the cholesterol levels between AGA and control groups. The serum total cholesterol, TG and LDL cholesterol levels were significantly higher in the AGA group than in the control group, and the standardized mean differences were 0.377 (95% confidence interval [CI]: 0.182-0.572, P < 0.001), 0.426 (95% CI: 0.164-0.688, P = 0.001) and 0.450 (95% CI: 0.171-0.728, P = 0.002) respectively. In addition, HDL cholesterol level was significantly lower in the AGA group than in the control group, and the standardized mean difference was -0.248 (95% CI: -0.472 to -0.023, P = 0.030). CONCLUSIONS: AGA patients showed statistically significant abnormal lipid profiles, and this might partly explain the association between AGA and cardiovascular diseases.

Direct correlation of structural and electrical properties of electron-doped individual VO2 nanowires on devised TEM grids.

Nano-scale VO2 wires with controlled parameters such as electron-doping have attracted intense interest due to their capability of suppressing the temperature of the metal-insulator transition (MIT). However, because their diameters are smaller than the spatial resolutions of the conventional measuring equipment, the ability to perform a thorough examination of the wires has been hindered. Here, we report the fabrication of a transmission electron microscopy (TEM) grid with an optimum design of Si3N4 windows on which the photolithography for individual electron-doped VO2 nanowire devices can be safely accomplished, allowing the cross-examination of the structural and electrical properties. TEM dark-field imaging was used to quantitatively investigate the fractions of rutile and M1 phases, and their lattice alignments were observed using high-resolution TEM (HRTEM) with small area diffraction. Moreover, electron energy loss spectroscopy (EELS) revealed that the rutile domain would be created by the strain induced by oxygen vacancies. Importantly, we successfully tuned the transition temperature by changing the rutile fraction while maintaining a high level of resistivity change. The resistivity at room temperature linearly decreased with the rutile fraction, following a simple model. Furthermore, the T dependence of the threshold voltage can be attributed to the Joule heating, exhibiting an identical thermal dependence, irrespective of the rutile fraction.

Inhibition of pulmonary cancer progression by epidermal growth factor receptor-targeted transfection with Bcl-2 and survivin siRNAs.

Clinical application of small interfering RNA (siRNA) in cancer therapy has been limited by the lack of an efficient systemic siRNA delivery system. In this report we describe an efficient siRNA delivery system directed to metastasized tumors, especially in the lungs. Anticancer siRNA was condensed in the presence of 9-arginine peptides (9Arg) and then complexed with cationic O,O'-dimyristyl-N-lysyl glutamate liposomes conjugated to antibodies against the epidermal growth factor receptor (EGFR). The ternary complex of optimized anti-EGFR-9Arg-lipoplexes exhibited efficient siRNA transfection of LS174T-Luc cancer cells grown in culture or orthotopically in mouse lungs. Anti-tumor Bcl-2/survivin siRNAs loaded in the anti-EGFR-9Arg-lipoplexes effectively suppressed transcription of their target genes, resulting in an efficient cancer cell death. Repeated intravenous administrations of the anti-EGFR-9Arg-lipoplexes effectively inhibited tumor growth in the mouse lungs and prolonged survival of the mice compared with nontargeted lipoplexes. These results suggest that the ternary complexes of anti-EGFR-9Arg-lipoplexes might have clinical applications in RNA interference cancer therapy.

Compensatory fronto-parietal hyperactivation during set-shifting in unmedicated patients with Parkinson's disease.

Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as mental rigidity, which can be measured as impaired set-shifting. Previous studies have shown that set-shifting deficits in patients with PD result from hypo-excitation of the caudate nucleus and lateral prefrontal cortices. The results of these studies may have been influenced by the inclusion of patients on dopaminergic medication, and by choosing set-shifting paradigms in which performance also depends on other cognitive mechanisms, such as matching-to-sample. To circumvent these potential confounding factors, we tested patients with PD that were not on dopamine replacement therapy, and we developed a new feedback-based paradigm to measure the cognitive construct set-shifting more accurately. In this case-control study, 18 patients with PD and 35 well-matched healthy controls performed the set-shifting task, while task-related neural activation was recorded using functional magnetic resonance imaging. Behaviourally, PD patients, compared with healthy controls, made more errors during repeat trials, but not set-shift trials. The patients, compared with controls, showed increased task-related activation of the bilateral inferior parietal cortex, and the right superior frontal gyrus, and decreased activation of the right ventrolateral prefrontal cortex during set-shift trials. Our findings suggest that, despite decreased task-related activation of the right ventrolateral prefrontal cortex, these early-stage unmedicated patients with PD do not yet suffer from set-shifting deficits due to compensatory hyperactivation in the inferior parietal cortex and the superior frontal gyrus.

Real time observation of ZnO nanostructure formation via the solid-vapor and solid-solid-vapor mechanisms.

We report in situ transmission electron microscopy studies of the formation of ZnO nanostructures--nanoscale depressions, nanoholes, nanoribbons, and nanosheets--and the phase stability and kinetics of Au catalysts on ZnO. During annealing, the ZnO layer produces hexagonally shaped, vertical nanoscale depressions, which increase in size along the 〈 0001 〉 growth direction through preferential dissociation from the {101[combining macron]0} facet and which subsequently form hexagonal islands at their six-fold junctions. Real time observations of the annealing of Au deposited on ZnO show that the catalysts remain solid up to 900 °C, an observation that has implications regarding ZnO nanowire growth via the vapor-solid-solid mechanism (VSS). The Au also creates hexagonal nanoscale holes only at the location of solid Au catalysts, via the solid-solid-vapor (SSV) mechanism. Importantly, coarsening of the Au particles is negligible due to limited Au diffusion on the side facets of the nanoscale depressions, suggesting an approach to the growth of uniform hybrid nanowires with control over both diameter and location. Furthermore, we directly monitor the evolution of the transformation of a nanoribbon into a nanosheet with {101[combining macron]0} facets. This process takes place through a periodic, kinetic roughening transition of the surface, which is controlled by the kinetic competition between surface growth and the transfer of evaporated gases. In total, these observations give new insights into multiple growth processes occurring in this important materials system.

Homocysteine, folate and pregnancy outcomes.

The purpose of this study is to evaluate the relationship between maternal and/or cord blood folate/homocysteine concentrations and adverse pregnancy outcomes. The study population included a random sample of singleton pregnant women in whom we measured total homocysteine and folic acid in maternal or cord blood at deliveries. A total of 227 pregnant women were enrolled. The concentration of folate in maternal blood tended to be significantly lower in pre-term birth than in full-term delivery group (median (95% CI), 14.4 (3.6-73) vs 25 (7.3-105.5) p < 0.01). The total homocysteine in maternal and cord blood was significantly higher in the pre-eclampsia than in the normotensive group (7.9 (1.7-28.2) vs 5.9 (1.8-14.6) µmol/ml, p < 0.05; and 5.8 (2.6-14.4) vs 4.2 (0.7-7.9) ng/ml, p < 0.05, respectively). Lower maternal serum folate concentration is associated with pre-term delivery and higher maternal plasma homocysteine concentration with pre-eclampsia.

Can migraine prophylaxis prevent acute mountain sickness at high altitude?

Acute mountain sickness (AMS) develops in people trekking at high altitude. The underlying mechanism is vasodilation due to low pressure of oxygen. However, individual susceptibility for AMS is unknown, thus, one cannot predict when or to whom it happens. Because AMS usually begins with headache, and because migraineurs are more vulnerable to AMS, we studied by the literatures review on the mechanism and clinical features in common, and assessed the treatment modalities for both disorders. This led to us the following hypothesis that, migraine prophylaxis may prevent or delay the onset of AMS at high altitude. Clinical features of AMS include nausea or vomiting when it progresses. Hypobaric hypoxia, dehydration or increased physical exertion trigger or aggravate both disorders. In migraine, cerebral vasodilation can happen following alteration of neuronal activity, whereas the AMS is associated with peripheral vessel dilation. Medications that dilate the vessels worsen both conditions. Acute treatment strategies for migraine overlap with to those of AMS, including drugs such as vasoconstrictors, or other analgesics. To prevent AMS, adaptation to high altitude or pharmacological prophylaxis, i.e., acetazolamide has been recommended. This carbonic anhydrase inhibitor lowers serum potassium level, and thus stabilizes membrane excitability. Acetazolamide is also effective on specific forms of migraine. Taken together, these evidences implicate that migraine prophylaxis may prevent or delay the onset of AMS by elevating the threshold for high altitude.

Monte carlo simulations of tau proteins: effect of phosphorylation.

We perform Monte Carlo simulations of tau proteins bound to a cylinder that mimics a microtubule (MT), and then study them in solution. Tau protein binds to a highly anionic MT surface to stabilize the cylindrical structure of MT. The negatively charged tail domain floats away from the anionic MT surface while positively charged tau segments localize near the MT surface. Monte Carlo simulations demonstrate that, in 3RS tau isoform (which has three imperfect repeats (R) short (S) isoform), amino acids are more condensed near a highly charged interface compared to 4RL isoform (which has four imperfect repeats (R) long (L) isoform). In 4RL isoform, amino acids in tail domain stay mostly apart from the MT surface. In the bulk solution, dephosphorylated taus are separated due to Coulomb repulsion between similarly charged isoforms. Moderate phosphorylation of 3RS isoform decreases average intermolecular distance between dephosphorylated and phosphorylated taus and lead to their overlap. Further phosphorylation does not change noticeably the intermolecular distances.

Lamellar phase coexistence induced by electrostatic interactions.

Membranes containing highly charged biomolecules can have a minimal free-energy state at small separations that originates in the strongly correlated electrostatic interactions mediated by counterions. This phenomenon can lead to a condensed, lamellar phase of charged membranes that coexists in thermodynamic equilibrium with a very dilute membrane phase. Although the dilute phase is mostly water, entropy dictates that this phase must contain some membranes and counterions. Thus, electrostatics alone can give rise to the coexistence of a condensed and an unbound lamellar phase. We use numerical simulations to predict the nature of this coexistence when the charge density of the membrane is large, for the case of multivalent counterions and for a membrane charge that is characteristic of biomolecules. We also investigate the effects of counterion size and salt on the two coexisting phases. With increasing salt concentration, we predict that electrostatic screening by salt can destroy the phase separation.

Electrophysiological evidence for endogenous control of attention in switching between languages in overt picture naming.

Language switching in bilingual speakers requires attentional control to select the appropriate language, for example, in picture naming. Previous language-switch studies used the color of pictures to indicate the required language thereby confounding endogenous and exogenous control. To investigate endogenous language control, our language cues preceded picture stimuli by 750 msec. Cue-locked event-related potentials (ERPs) were measured while Dutch-English bilingual speakers overtly named pictures. The response language on consecutive trials could be the same (repeat trials) or different (switch trials). Naming latencies were longer on switch than on repeat trials, independent of the response language. Cue-locked ERPs showed an early posterior negativity for switch compared to repeat trials for L2 but not for L1, and a late anterior negativity for switch compared to repeat trials for both languages. The early switch-repeat effect might reflect disengaging from the nontarget native language, whereas the late switch-repeat effect reflects engaging in the target language. Implications for models of bilingual word production are discussed.

Frontal-striatal abnormalities underlying behaviours in the compulsive-impulsive spectrum.

In this paper, we tentatively bring together the psychiatric, neurological and addiction perspectives on the impulsive-compulsive spectrum of neuropsychiatric disorders, in order to understand the pathophysiology of impulse control disorders (ICDs) in Parkinson's disease. In an attempt to try to pool the various levels of information we will therefore focus on three disorders within the impulse-compulsive spectrum, i.e., obsessive-compulsive disorder (OCD), ICDs in Parkinson's disease, and cocaine seeking behaviour. Whereas there are large differences between these three domains, each with their own nomenclature, hypotheses and study results, they share the focus on an imbalance within and between the frontal-striatal circuits as underlying substrate for the behaviours. For each disorder, we summarize the results from recent studies in order to describe in which way alterations in the frontal-striatal circuits contribute to the phenotype. The phenomenological overlap between ICDs in Parkinson's disease, addiction and OCD needs further investigation, since better understanding of the overlapping and differentiating characteristics will contribute to our understanding of the pathophysiology of the disturbances and treatment alternatives.

Human microtubule-associated-protein tau regulates the number of protofilaments in microtubules: a synchrotron x-ray scattering study.

Microtubules (MTs), a major component of the eukaryotic cytoskeleton, are 25 nm protein nanotubes with walls comprised of assembled protofilaments built from alphabeta heterodimeric tubulin. In neural cells, different isoforms of the microtubule-associated-protein (MAP) tau regulate tubulin assembly and MT stability. Using synchrotron small angle x-ray scattering (SAXS), we have examined the effects of all six naturally occurring central nervous system tau isoforms on the assembly structure of taxol-stabilized MTs. Most notably, we found that tau regulates the distribution of protofilament numbers in MTs as reflected in the observed increase in the average radius R(MT) of MTs with increasing Phi, the tau/tubulin-dimer molar ratio. Within experimental scatter, the change in R(MT) seems to be isoform independent. Significantly, R(MT) was observed to rapidly increase for 0 < Phi < 0.2 and saturate for Phi between 0.2-0.5. Thus, a local shape distortion of the tubulin dimer on tau binding, at coverages much less than a monolayer, is spread collectively over many dimers on the scale of protofilaments. This implies that tau regulates the shape of protofilaments and thus the spontaneous curvature C(o)(MT) of MTs leading to changes in the curvature C(MT) (=1/R(MT)). An important biological implication of these findings is a possible allosteric role for tau where the tau-induced shape changes of the MT surface may effect the MT binding activity of other MAPs present in neurons. Furthermore, the results, which provide insight into the regulation of the elastic properties of MTs by tau, may also impact biomaterials applications requiring radial size-controlled nanotubes.

Hepatic resection for hepatocellular carcinoma meeting Milan criteria in Child-Turcotte-Pugh class a patients with cirrhosis.

This study evaluated whether hepatic resection is a reasonable strategy as an initial treatment for hepatocellular carcinoma (HCC) meeting Milan criteria in patients with compensated cirrhosis. From the database of 435 consecutive patients with resection of HCC between July 1994 and May 2007, 213 patients were found to have Child-Turcotte-Pugh class A cirrhosis and HCC meeting Milan criteria, as shown by preoperative image studies. We examined long-term survivals and patterns of recurrence after hepatic resection among those patients. Overall survival rates at 1, 3, 5, and 10 years were 92%, 78%, 69%, and 52%, respectively, and 1-, 3-, 5-, and 10-year disease-free survival rates were 79%, 57%, 44%, and 19%, respectively. Pathological review indicated that 36/213 patients (16.9%) had another nodule and/or gross vascular invasion. Microvascular invasion, tumor size, and histological grade of cirrhosis were independent risk factors for recurrence. Sixty percent of recurrent cases met the Milan criteria. The six patients who underwent living donor salvage liver transplantation (OLT) for intrahepatic recurrence were alive without recurrence at a median of 24 (range = 8-31) months. These favorable data suggest that hepatic resection is a good option for small HCCs in patients with compensated cirrhosis; and salvage OLT may be reserved for patients with recurrences.

Duct-to-duct biliary reconstructions and complications in 100 living donor liver transplantations.

OBJECTIVE: We evaluated the risk factors for biliary complications and surgical procedures for duct-to-duct reconstructions in adult living donor liver transplantation (LDLT). PATIENTS AND METHODS: From February 2005 to March 2008, we performed 100 cases of adult LDLT with duct-to-duct biliary reconstruction, using 64 right lobe grafts, 33 left lobe grafts, and 3 right lateral grafts. We employed 4 types of duct-to-duct procedures: all interrupted 6-0 Prolene suture (group 1, n = 9); continuous posterior and interrupted anterior wall 6-0 Prolene suture (group 2, n = 49); all continuous 7-0 Prolene suture (group 3, n = 26); and all continuous 7-0 Prolene suture with external stent (group 4, n = 16). Biliary complications were defined as an anastomosis stricture or a leakage. RESULTS: Thirty-four patients experienced biliary complications during the follow-up period (median, 27 months). The incidence of stricture was 27% and that of leakage, 8%. There were no perioperative, intraoperative, or anatomic risk factors for biliary complications, except the type of duct-to-duct procedure. Group 1 and 2 patients showed higher incidences of biliary strictures than groups 3 and 4 (43.1% vs 4.7%; P = .00). Group 3 patients experienced a higher incidence of bile leakage than the other groups (23.1% vs 2.7%; P = .004). CONCLUSIONS: The type of biliary reconstruction is a factor affecting biliary complications following duct-to-duct anastomosis in LDLT. Duct-to-duct biliary anastomosis with 7-0 monofilament suture and a small external stent is a feasible procedure in LDLT that significantly reduces the incidence of biliary complications.

A numerical study of the electrostatic properties of two finite-width charged dielectric slabs in water.

A numerical algorithm based on the image charge method is introduced to calculate the electrostatic potential, energy, and forces present in systems involving multiple point charges embedded in an inhomogeneous dielectric environment composed of five parallel dielectric slabs. The methodology is implemented within Monte Carlo simulations to calculate the thermal properties of two charged dielectric plates of finite thickness immersed in water.