Distal hereditary motor neuropathy (dHMN) comprises a heterogeneous group of inherited disorders associated with neurodegeneration of motor nerves and neurons, mainly charac-terized by progressive ...atrophy and weakness of distal muscle without clinical or electrophysiological sensory abnormalities. To improve the recognition and diagnosis of the disease, we summarized the clinical manifestations, electrophysiological, pathological, and genetic characteristics in eight patients with dHMN.
Eight probands from different families diagnosed with dHMN were recruited in this study between June 2018 and April 2019 at Peking University People's Hospital. Eight patients underwent complete neurological examination and standard electrophysiological examinations. The clinical criteria were consistent with the patients presenting with a pure motor neuropathy with no sensory changes on electrophysiology. The detailed clinical symptoms, neurophysiological examinations, pathological features and gene mutations were analyzed re
Background
Postoperative nausea and vomiting (PONV) are common complications following surgery and anaesthesia. Antiemetic drugs are only partially effective in preventing PONV. An alternative ...approach is to stimulate the PC6 acupoint on the wrist. This is an update of a Cochrane review first published in 2004, updated in 2009 and now in 2015.
Objectives
To determine the effectiveness and safety of PC6 acupoint stimulation with or without antiemetic drug versus sham or antiemetic drug for the prevention of PONV in people undergoing surgery.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 12, 2014), MEDLINE (January 2008 to December 2014), EMBASE (January 2008 to December 2014), ISI Web of Science (January 2008 to December 2014), World Health Organization Clinical Trials Registry, ClinicalTrials.gov, and reference lists of articles to identify additional studies. We applied no language restrictions.
Selection criteria
All randomized trials of techniques that stimulated the PC6 acupoint compared with sham treatment or drug therapy, or combined PC6 acupoint and drug therapy compared to drug therapy, for the prevention of PONV. Interventions used in these trials included acupuncture, electro‐acupuncture, transcutaneous electrical acupoint stimulation, transcutaneous nerve stimulation, laser stimulation, capsicum plaster, acu‐stimulation device, and acupressure in people undergoing surgery. Primary outcomes were the incidences of nausea and vomiting after surgery. Secondary outcomes were the need for rescue antiemetic therapy and adverse effects.
Data collection and analysis
Two review authors independently extracted the data and assessed the risk of bias domains for each trial. We used a random‐effects model and reported risk ratio (RR) with associated 95% confidence interval (95% CI). We used trial sequential analyses to help provide information on when we had reached firm evidence in cumulative meta‐analyses of the primary outcomes, based on a 30% risk ratio reduction in PONV.
Main results
We included 59 trials involving 7667 participants. We rated two trials at low risk of bias in all domains (selection, attrition, reporting, blinding and other). We rated 25 trials at high risk in one or more risk‐of‐bias domains. Compared with sham treatment, PC6 acupoint stimulation significantly reduced the incidence of nausea (RR 0.68, 95% CI 0.60 to 0.77; 40 trials, 4742 participants), vomiting (RR 0.60, 95% CI 0.51 to 0.71; 45 trials, 5147 participants) and the need for rescue antiemetics (RR 0.64, 95% CI 0.55 to 0.73; 39 trials, 4622 participants). As heterogeneity among trials was substantial and there were study limitations, we rated the quality of evidence as low. Using trial sequential analysis, the required information size and boundary for benefit were reached for both primary outcomes.
PC6 acupoint stimulation was compared with six different types of antiemetic drugs (metoclopramide, cyclizine, prochlorperazine, droperidol. ondansetron and dexamethasone). There was no difference between PC6 acupoint stimulation and antiemetic drugs in the incidence of nausea (RR 0.91, 95% CI 0.75 to 1.10; 14 trials, 1332 participants), vomiting (RR 0.93, 95% CI 0.74 to 1.17; 19 trials, 1708 participants), or the need for rescue antiemetics (RR 0.87, 95% CI 0.65 to 1.16; 9 trials, 895 participants). We rated the quality of evidence as moderate, due to the study limitations. Using trial sequential analyses, the futility boundary was crossed before the required information size was surpassed for both primary outcomes.
Compared to antiemetic drugs, the combination of PC6 acupoint stimulation and antiemetic therapy reduced the incidence of vomiting (RR 0.56, 95% CI 0.35 to 0.91; 9 trials, 687 participants) but not nausea (RR 0.79, 95% CI 0.55 to 1.13; 8 trials, 642 participants). We rated the quality of evidence as very low, due to substantial heterogeneity among trials, study limitations and imprecision. Using trial sequential analysis, none of the boundaries for benefit, harm or futility were crossed for PONV. The need for rescue antiemetic was lower in the combination PC6 acupoint stimulation and antiemetic group than the antiemetic group (RR 0.61, 95% CI 0.44 to 0.86; 5 trials, 419 participants).
The side effects associated with PC6 acupoint stimulation were minor, transient and self‐limiting (e.g. skin irritation, blistering, redness and pain) in 14 trials. Publication bias was not apparent in the contour‐enhanced funnel plots.
Authors' conclusions
There is low‐quality evidence supporting the use of PC6 acupoint stimulation over sham. Compared to the last update in 2009, no further sham comparison trials are needed. We found that there is moderate‐quality evidence showing no difference between PC6 acupoint stimulation and antiemetic drugs to prevent PONV. Further PC6 acupoint stimulation versus antiemetic trials are futile in showing a significant difference, which is a new finding in this update. There is inconclusive evidence supporting the use of a combined strategy of PC6 acupoint stimulation and antiemetic drug over drug prophylaxis, and further high‐quality trials are needed.
The effects of recovery on the subsequent recrystallization of tantalum were investigated via two-step annealing at two temperatures. Transmission electron microscopy, electron back-scattered ...diffraction, and X-ray diffraction were employed to determine the respective microstructures and textures after various annealing regimes. The results show that many large grains with {111} orientations are developed when heating at 1573 K without pre-recovery, while pre-recovery can introduce a homogeneous fine microstructure and weaken the texture. This difference can be attributed to the recovery-induced change in nucleation mechanisms. Elongated grains stretch along grain boundaries or locate in the interior of deformed grains, mainly due to the heterogeneous distribution of stored energy. Dislocations characterized by submicron bands in the deformed state evolve into sub-grains during pre-recovery and grow continuously, indicating a homogeneous distribution of dislocation or stored energy after pre-recovery, which can significantly influence subsequent nucleation and grain growth.
Neuroblastoma (NB) is the most common extracranial neoplasm in children. In NB, loss of p53 function is largely due to cytoplasmic sequestration rather than mutation. Ubiquitin-conjugating enzyme E2 ...N (UBE2N), also known as Ubc13, is an E2 ubiquitin-conjugating enzyme that promotes formation of monomeric p53 that results in its cytoplasmic translocation and subsequent loss of function. Therefore, inhibition of UBE2N may reactivate p53 by promoting its nuclear accumulation. Here, we show that NSC697923, a novel UBE2N inhibitor, exhibits potent cytotoxicity in a panel of NB cell lines evidenced by its ability to induce apoptosis. In p53 wild-type NB cells, NSC697923 induced nuclear accumulation of p53, which led to its increased transcriptional activity and tumor suppressor function. Interestingly, in p53 mutant NB cells, NSC697923 induced cell death by activating JNK pathway. This effect was reversible by blocking JNK activity with its selective inhibitor, SP600125. More importantly, NSC697923 impeded cell growth of chemoresistant LA-N-6 NB cell line in a manner greater than conventional chemotherapy drugs doxorubicin and etoposide. NSC697923 also revealed in vivo antitumor efficacy in NB orthotopic xenografts. Taken together, our results suggest that UBE2N is a potential therapeutic target in NB and provide a basis for the rational use of UBE2N inhibitors like NSC697923 as a novel treatment option for NB patients.
This paper was attempted to investigate the microstructure degradation and low cycle fatigue (LCF) performance of a serviced K465 Ni‐based superalloy turbine blade. LCF tests were carried out with ...small‐scale plate specimens sampled from the blades. Relationship between residual LCF life and microstructure state was estimated. The results indicate that the coarsening of γ/γ′ phases was the most significant microstructure degradation mode for the serviced blades. Both the γ matrix width and the γ′ precipitate diameter increased with the increase of service duration, while the γ′ precipitate volume fraction slightly decreased. The most severe microstructure degradation occurred at the leading edge along the chord direction, particularly at 50–70 % airfoil spans. The residual LCF life exhibited an accelerated decrease characteristic as increases of microstructure degradation degree. The coarsened microstructure diminished shear resistance of the superalloy, which resulted in additional accumulated inelastic deformation and a corresponding reduction in LCF life.
Highlights
Service induced microstructure evolution and LCF life decay of a blade were investigated.
Coarsening was identified as the main degradation form of γ/γ' phases in serviced blade.
Accelerated decrease of residual LCF life was identified as increases of coarsening.
Reduced plastic deformation resistance owing to coarsening is crucial to decay LCF life.
There is an unmet need for greater investment in preparedness against major epidemics and pandemics. The arguments in favour of such investment have been largely based on estimates of the losses in ...national incomes that might occur as the result of a major epidemic or pandemic. Recently, we extended the estimate to include the valuation of the lives lost as a result of pandemic-related increases in mortality. This produced markedly higher estimates of the full value of loss that might occur as the result of a future pandemic. We parametrized an exceedance probability function for a global influenza pandemic and estimated that the expected number of influenza-pandemic-related deaths is about 720 000 per year. We calculated that the expected annual losses from pandemic risk to be about 500 billion United States dollars - or 0.6% of global income - per year. This estimate falls within - but towards the lower end of - the Intergovernmental Panel on Climate Change's estimates of the value of the losses from global warming, which range from 0.2% to 2% of global income. The estimated percentage of annual national income represented by the expected value of losses varied by country income grouping: from a little over 0.3% in high-income countries to 1.6% in lower-middle-income countries. Most of the losses from influenza pandemics come from rare, severe events.
Accurate and quick acquisition of hydrogeological parameters is the critical issue for groundwater numerical simulation and sustainability of the water sources. A novel intelligent inversion method ...of hydrogeological parameter, based on the global optimization algorithm called the disturbance-inspired equilibrium optimizer (DIEO), is developed. Firstly, the mathematical model and the framework of DIEO are reported. Several types of mathematical benchmark functions are used to test the performance of the DIEO. Furthermore, the intelligent inversion of hydrogeological parameters of pumping tests is transformed into the global optimization problem, which can be solved by meta-heuristic algorithms. The objective function for hydrogeological parameter inversion is constructed, and the novel inversion method based on DIEO is finally proposed. To further validate the competitiveness and efficiency of the proposed intelligent inversion method, three types of case studies are carried out. The results show that the proposed intelligent inversion method is reliable for obtaining the hydrogeological parameters accurately and quickly, providing a reference for the inversion of parameters in other fields.
Coincident with an increasing national interest in equitable health care, a number of studies have described disparities in access to solid organ transplantation for minority patients. In contrast, ...relatively little is known about differences in posttransplant outcomes between patients of specific racial and ethnic populations. In this paper, we review trends in access to solid organ transplantation and posttransplant outcomes by organ type, race and ethnicity. In addition, we present an analysis of categories of factors that contribute to the racial/ethnic variation seen in kidney transplant outcomes. Disparities in minority access to transplantation among wait‐listed candidates are improving, but persist for those awaiting kidney, simultaneous kidney and pancreas and intestine transplantation. In general, graft and patient survival among recipients of solid organ transplants is highest for Asians and Hispanic/Latinos, intermediate for whites and lowest for African Americans. Although much of the difference in outcomes between racial/ethnic groups can be accounted for by adjusting for patient characteristics, important observed differences remain. Age and duration of pretransplant dialysis exposure emerge as the most important determinants of survival in an investigation of the relative impact of center‐related versus patient‐related variables on kidney graft outcomes.
Solid organ transplant outcomes vary among racial and ethnic groups in the United States; observed patient and center characteristics do not account fully for these differences among kidney transplant recipients.
A new non-classical theory of elastic dielectrics is developed using the couple stress and electric field gradient theories that incorporates the couple stress, quadrupole and curvature-based ...flexoelectric effects. The couple stress theory and an extended Gauss’s law for elastic dielectrics with quadrupole polarization are applied to derive the constitutive relations of this new theory through energy conservation. The governing equations and the complete boundary conditions are simultaneously obtained through a variational formulation based on the Gibbs-type variational principle. The constitutive relations of general anisotropic and isotropic materials with the corresponding independent material constants are also provided, respectively. To illustrate the newly proposed theory and to show the flexoelectric effect in isotropic materials, one pure bending problem of a simply supported beam is analytically solved by directly applying the formulas derived. The analytical results reveal that the flexoelectric effect is present in isotropic materials. In addition, the incorporation of both the couple stress and flexoelectric effects always leads to increased values of the beam bending stiffness.
A reduced size rat-race coupler, incorporating a bandpass frequency response characteristic, is presented and designed based on substrate-integrated waveguide (SIW) technology. By use of electric- ...and magnetic-coupling structures between adjacent SIW cavity resonators, a conventional rat-race coupler and a bandpass filter with a 200-MHz bandwidth at a centre frequency of 7.75 GHz can be integrated as one component resulting in miniaturisation. A design process based on the coupled-resonator network is introduced to synthesise such a bandpass coupler with desired bandwidth, return loss and coupling. A Butler matrix and a six-port junction with bandpass response are then developed based on the proposed rat-race coupler. They represent excellent candidates for miniaturised transceiver and direct conversion systems. The measured results are in good agreement with the simulated predictions.
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