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Children are susceptible to allergic rhinitis (caused by external allergens) accompanied by functional gastrointestinal disease, which seriously affects physical and mental health. Antihistamines and nasal spray hormones are commonly used in clinical treatment, but these drugs often have unsatisfactory efficacy and result in high recurrence rates. Therefore, understanding the pathogenesis of allergic rhinitis with functional gastrointestinal disease and seeking safer treatment and prevention methods is essential. Herein, molecular ecology and immunoassays were used to analyze correlations between pediatric allergic rhinitis with functional gastrointestinal disease and both the intestinal microbiota and gastrointestinal peptide levels. Fifty healthy children (healthy group) and 80 children with allergic rhinitis with functional gastrointestinal disease (case group: evenly divided into a control group (conventional drug therapy) and an intervention group (conventional drug therapy + glutamine+probiotics)), were enrolled. Bifidobacterium and Lactobacillus counts and the gastrin and motilin levels were lower in the case group than in the healthy group, whereas Enterobacter, yeast, and Enterococcus counts and the somatostatin, serotonin, and vasoactive intestinal peptide levels were higher. Post treatment, intestinal microbiota indices, gastrointestinal peptide levels, and intestinal barrier function were better in the intervention group than in the control group ( p < 0.05). The intervention group had a significantly higher total therapeutic response rate (95.00%) than the control group (77.50%). The intestinal microbiota was closely associated with gastrointestinal peptide levels. Treatment with glutamine and probiotics regulated these levels, re-established balance in the intestinal microbiota, and restored intestinal barrier function.

Introduction and Objective Onasemnogene abeparvovec (formerly AVXS-101), is designed to address the genetic root cause of spinal muscular atrophy (SMA), survival motor neuron 1 gene (SMN1) deletion/mutation. Here, we evaluate final data from STR1VE-US (NCT03306277), a multicenter, open-label, single-arm, single-dose, Phase 3 study conducted in the United States, investigating efficacy and safety of one-time intravenous infusion of onasemnogene abeparvovec in patients with SMA1 (aged, Methods Co-primary endpoints: independent sitting for ≥30 seconds at the 18 months visit, survival (no death/permanent ventilation) at 14 months of age. Co-secondary endpoints: ability to thrive at 18 months (composite of: tolerates thin liquids, no mechanical nutrition support, maintains weight consistent with age), independence from ventilatory support at 18 months (based on Trilogy BiPAP usage). Safety endpoints: unanticipated treatment-related toxicity of Grade ≥3 based on CTCAE. Results All co-primary and co-secondary endpoints demonstrated statistically significant benefits of onasemnogene abeparvovec compared with untreated controls in the Pediatric Neuromuscular Clinical Research (PNCR) study. Thirteen of 22 (59.1%) patients treated with onasemnogene abeparvovec achieved the milestone of functional independent sitting for ≥30 seconds at the 18-month visit (P Conclusions In the STR1VE-US study, patients with SMA1 treated with onasemnogene abeparvovec demonstrated a significant therapeutic benefit and a favourable the benefit-risk profile.

Background and aim Balance deficits are common after total knee arthroplasty (TKA); however the responsiveness of commonly used balance measurement tools has not been well defined. The objective of this prospective study was to compare the internal and external responsiveness of four measurement tools in assessing recovery of balance function following TKA. Methods A total of 134 individuals with TKA (95 women; age: 66.3 ± 6.6 years) completed the Balance Evaluation Systems Test (BESTest), Mini-BESTest, Brief-BESTest, and Berg Balance Scale (BBS) at 2, 4, 8, 12, and 24 weeks post-TKA. The Functional Gait Assessment (FGA) served as the anchor measure, and was also measured across these time points. Internal responsiveness was indicated by the standardized response mean (SRM), while external responsiveness was reflected by the degree of association of the changes of balance scores with those of FGA. Results The SRM ranged from 0.60–1.14 for the BESTest, 0.40–0.94 for the Mini-BESTest, 0.27–0.91 for the Brief-BESTest, and 0.19–0.70 for the BBS, over time. The change in BESTest and Mini-BESTest scores predicted the change in the FGA scores across all time periods, except for the Mini-BESTest between weeks 12–24, accounting for 13–27%, and 12–24% of the variance, respectively. The Brief-BESTest scores only predicted FGA scores between the weeks 2–4 ( R 2 = 20%). The changes in BBS scores were not associated with the FGA. Conclusion The BESTest is the most responsive in measuring recovery of balance among individuals with TKA. The Mini-BESTest is a reasonable option during time constraints.

Summary There is substantial inter-individual variability in serum testosterone levels in hypogonadal men treated with testosterone gels. We aimed to elucidate participant-level factors that contribute to inter-individual variability in testosterone levels during testosterone therapy. An exploratory aim was to determine whether polymorphisms in genes encoding testosterone-metabolizing enzymes could explain the variation in on-treatment testosterone concentrations in men who were randomized to testosterone arm in TOM Trial. We used data from three randomized trials that used 1% transdermal testosterone gels and had testosterone levels measured 2–4 weeks after randomization for dose adjustment: Testosterone in Older Men with Mobility Limitation (TOM), Effects of Testosterone on Pain Perception (TAP), and Effects of Testosterone on Atherosclerosis Progression (TEAAM). Forty-seven percent, 38%, and 9% of participants in TAP, TEAAM, and TOM trials, respectively, failed to raise testosterone levels >400 ng/dL; 6, 8, and 30% of participants had on-treatment testosterone levels >1000 ng/dL. Even after dose adjustment, there was substantial variation in on-treatment levels at subsequent study visits. Baseline characteristics (age, height, weight, baseline testosterone, SHBG, hematocrit, and creatinine) accounted for only a small fraction of the variance (

Vision loss can result from common eye diseases and continue to be a major disability due to its dramatic effect on the quality of life of patients. Injuries to the retina lead to visual impairment in age-related macular degeneration and diabetic retinopathy, while injuries to the optic nerve cause loss of vision in glaucoma. Other injuries to the cornea can also cause scarring and subsequent blindness. Current therapies are limited at halting or minimizing disease progression while cure and restoration of vision remain a challenge for many common eye diseases. Stem cell-based therapy is a promising treatment to restore vision in patients with retinal diseases or ocular surface injury. Transplantation of stem cells from various sources including embryonic stem cells, induced pluripotent stem cells, retinal progenitor cells, and limbal stem cells has been used in repairing and replacing nonfunctioning cells. Stem cell-based therapy will continue to be an exciting field of research, and its potential for clinical therapy has just begun to unravel.

This paper discusses the performance and reliability of the third generation split-gate flash memory cell (ESF3) successfully embedded in a high performance and low power 28 nm logic process technology. The scaling of the 1.05V select transistor is demonstrated with the excellent program and erase efficiency and the 1M program/erase (P/E) cycle endurance capability. The silicon result of a 4Mb test chip and a 32Mb design will be also be shown.

The commissioning of CSNS front end has been finished. The 15 mA beam intensity is obtained at the end of RFQ. For CSNS ion source, it is a type of penning surface plasma ion source, similar to ISIS ion source. To improve the operation stability and reduce spark, sonic improvements have been made, including Penning field and extraction optics. The codes PBGUNS and CST are applied to simulate the beam extraction. With these simulation results, various extracted structures are modified, including the jaw gap of extractor and the gap of between plasma slit and extractor. The running results show the stability of ion source is improved further.

A Radio Frequency (RF) H-minus source with external antenna is under construction to improve the performance of China Spallation Neutron Source (CSNS), which requires a H-minus beam of 40 mA peak current, 25 Hz repetition rate, and 1 ms pulse length. The plasma chamber is made of Si3N4 ceramic to endure high thermal shock. The water-cooled antenna is brazed on the outer wall of the plasma chamber to enhance heat dissipation of the chamber. The antenna is powered with a solid-state amplifier of maximum 80 kW via an isolation transformer and an impedance transformer. To produce a flat-top H-minus current, we aim to program the amplitude of RF input signal,so that the fluctuation of the beam current is compensated with the change of the RF power within a pulse. Up to now the mechanical construction of the source is finished, and the RF match network is ready for test. The source is scheduled to produce plasma in the end of 2017.

This paper describes a novel method to non-destructively determine the thickness of thin layer in a non-contact way. A model of wave interference was established based on the multireflection of shear wave in layered system. Furthermore, its expression of reflection coefficient phase was deduced to provide the principle of thickness measurement. A formed laser source by focusing a line on the layer surface was used to generate shear wave, while an electromagnetic acoustic testing (EMAT) sensor was proposed to receive the wave. An example of the method and experimental measurement for comparison is given for a thin steel sheet with the thickness of approximate 0·4 mm. The relative error between the present method and metallography method is less than 4%, which shows laser-EMAT technique is very suitable to non-destructive assess the thickness of the layer.

Background The phase III RAISE trial (NCT01183780) demonstrated that the vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 binding monoclonal antibody ramucirumab plus 5-fluororuracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo + FOLFIRI as second-line metastatic colorectal cancer (mCRC) treatment. To identify patients who benefit the most from VEGFR-2 blockade, the RAISE trial design included a prospective and comprehensive biomarker program that assessed the association of biomarkers with ramucirumab efficacy outcomes. Patients and methods Plasma and tumor tissue collection was mandatory. Overall, 1072 patients were randomized 1 : 1 to the addition of ramucirumab or placebo to FOLFIRI chemotherapy. Patients were then randomized 1 : 2, for the biomarker program, to marker exploratory (ME) and marker confirmatory (MC) groups. Analyses were carried out using exploratory assays to assess the correlations of baseline marker levels [VEGF-C, VEGF-D, sVEGFR-1, sVEGFR-2, sVEGFR-3 (plasma), and VEGFR-2 (tumor tissue)] with clinical outcomes. Cox regression analyses were carried out for each candidate biomarker with stratification factor adjustment. Results Biomarker results were available from >80% (n = 894) of patients. Analysis of the ME subset determined a VEGF-D level of 115 pg/ml was appropriate for high/low subgroup analyses. Evaluation of the combined ME + MC populations found that the median OS in the ramucirumab + FOLFIRI arm compared with placebo + FOLFIRI showed an improvement of 2.4 months in the high VEGF-D subgroup [13.9 months (95% CI 12.5–15.6) versus 11.5 months (95% CI 10.1–12.4), respectively], and a decrease of 0.5 month in the low VEGF-D subgroup [12.6 months (95% CI 10.7–14.0) versus 13.1 months (95% CI 11.8–17.0), respectively]. PFS results were consistent with OS. No trends were evident with the other antiangiogenic candidate biomarkers. Conclusions The RAISE biomarker program identified VEGF-D as a potential predictive biomarker for ramucirumab efficacy in second-line mCRC. Development of an assay appropriate for testing in clinical practice is currently ongoing. Clinical trials registration NCT01183780.

The commissioning of CSNS front end has been finished. Above 15 mA beam intensity is obtained at the end of RFQ. For CSNS ion source, it is a type of penning surface plasma ion source, similar to ISIS ion source. To improve the operation stability and reduce spark rate, some modifications have been performed, including Penning field, extraction optics and post acceleration. PBGUNS is applied to optimize beam extraction. The co-extraction electrons are considered at PBGUNS simulation and various extracted structure are simulated aiming to make the beam through the extracted electrode without loss. The stability of ion source is improved further.

Summary Acupuncture has been practiced empirically in China for several millennia, and is being increasingly accepted by practitioners and patients worldwide. Functional gastrointestinal disorders are common in clinical gastroenterology. The prevalence of one or more functional gastrointestinal disorders is estimated to be as high as 70% in general population using Rome diagnostic criteria. Since functional gastrointestinal disorders are diagnosed based on symptoms and the exact aetiologies for most of functional gastrointestinal disorders are not completely known, it is not unusual that the treatment for these disorders is unsatisfactory and alternative therapies are attractive to both patients and practitioners. During the latest decades, a considerable number of studies have been performed on acupuncture for the treatment of functional gastrointestinal disorders and underlying mechanisms. In this article, we reviewed available data in the literature on the applications and mechanisms of acupuncture for the treatment of functional gastrointestinal disorders, including functional oesophageal disorders, nausea and vomiting, functional dyspepsia, irritable bowel syndrome, constipation, etc. A summary is provided based on the quality and quantity of published studies regarding the efficacy of acupuncture in treating these various disorders. In addition, the methodology of acupuncture is also introduced.

The aim was to investigate the effects of electrical field stimulation (EFS) with long and short pulses on gastric emptying, gastric contractility and vagal activity in dogs. Sixteen dogs were equipped with a duodenal cannula, electrodes and strain gauges (10 dogs) in the stomach. Each dog was fed with Ensure and gastric effluent was collected from the cannula. Electrical stimulation was applied via two electrodes (about 12 cm apart, one in the corpus and the other in the antrum) with long pulses (a frequency of 6 cycles min-1, pulse amplitude of 6 mA and width of 100 ms) in 10 dogs and with short pulses (frequency of 30 Hz and pulse width of 300 micros) in six dogs. The electrocardiogram was also recorded and heart rate variability was derived to assess the vagal activity. It was found that: (i). EFS with long pulses did not alter gastric emptying during stimulation but increased gastric emptying during the 45 min immediately after stimulation; (ii). EFS with long pulses increased gastric contractility in both proximal and distal antrum during and after the stimulation; (iii). EFS with long pulses resulted in an increase in vagal tone during the 45 min immediately after stimulation. However, there is no difference during the 45 min period of stimulation; (iv). EFS with short pulses had no effect on gastric emptying. We concluded that long pulse gastric electrical field stimulation with one electrode in the corpus and the other electrode in the antrum has postponed effects on gastric emptying of liquid, gastric contractility and vagal activity.

The objective of this study was to assess the efficacy of diffusion-weighted MRI (DWI) in monitoring response to radiotherapy in high-risk prostate cancer (PC).This retrospective study included 78 patients with high-risk PC undergoing 3.0-T MRI (supplemented by DWI) before and after intensity-modulated radiotherapy (IMRT). Based on follow-up clinical examinations, patients were divided into two groups: the recurrence group (patients who suffered biochemical/clinical recurrence within 3 years, n = 13) and the non-recurrence group (patients who were recurrence free for over 3 years, n = 65). The apparent diffusion coefficient (ADC) values before and after IMRT were compared between these two groups. The receiver-operating characteristics (ROC) analysis was carried out to investigate the discriminatory capability for pre- and post-IMRT ADC values.The overall ADC values were 1.04 ± 0.18 × 10(-3) mm(2) s(-1) for PCs before IMRT and 1.45 ± 0.15 × 10(-3) mm(2) s(-1) after IMRT (p 0.001). A statistically significant difference in post-IMRT ADC values was noted between patients with and without recurrence (1.27 ± 0.14 × 10(-3) mm(2) s(-1) vs 1.49 ± 0.12 × 10(-3)mm(2) s(-1); p 0.001), although there was no statistical difference between them in pre-IMRT ADC values (1.00 ± 0.17 × 10(-3) mm(2) s(-1) vs 1.05 ± 0.18 × 10(-3) mm(2) s(-1); p = 0.31). The ROC curve analysis revealed that the post-IMRT ADC values could help identify patients suffering recurrences (area under the curve, 0.88; p 0.001).Marked increase in ADC values was observed in PC after radiotherapy, especially in good responders. DWI is a valuable tool for monitoring the response to radiotherapy.This study examined the relationship between ADC changes and tumour response to treatment of PC.

Background Animal studies have shown that regional anaesthesia and analgesia may prevent or attenuate the surgical stress response by preserving immune function and result in better long-term outcome. We have tested the hypothesis that patients with ovarian serous adenocarcinoma who had surgery with epidural anaesthesia and analgesia would have better long-term outcome than those who were given general anaesthesia (GA) and i.v. opioid analgesia. Methods A retrospective review of medical records identified 143 patients with ovarian serous adenocarcinoma who underwent surgery between January 1994 and October 2006 at the Sun Yat-sen University Cancer Center. Data in the analysis included age, anaesthesia–analgesia technique, ASA status, blood loss, transfusion, duration of surgery, status of preoperative cancer antigen 125, tumour size, International Federation of Gynecology and Obstetrics stage, histological grade, lymph node status, residual macroscopic tumour, and chemotherapy. Survival analysis was made with the main outcome measure of death. Results The 3- and 5-yr overall survival rates were 78% and 61% in the patient group who received epidural anaesthesia and analgesia (Group E, n =106), and 58% and 49% in the patient group who received GA and i.v. opioid analgesia (Group G, n =37), respectively. After adjusting for the other variables, Group G had a hazard ratio of 1.214 ( P =0.043) in a multivariable Cox regression model compared with Group E. Conclusions This retrospective analysis suggests that epidural anaesthesia and analgesia for ovarian serous adenocarcinoma surgery may reduce mortality during the initial years of follow-up.

The Dark Matter Time Projection Chamber collaboration recently reported a dark matter limit obtained with a 10 liter time projection chamber filled with CF4 gas. The 10 liter detector was capable of 2D tracking (perpendicular to the drift direction) and 2D fiducialization, and only used information from two CCD cameras when identifying tracks and rejecting backgrounds. Since that time, the collaboration has explored the potential benefits of photomultiplier tube and electronic charge readout to achieve 3D tracking, and particle identification for background rejection. The latest results of this effort is described here., Comment: Proceedings of the 3rd International conference on Directional Detection of Dark Matter (CYGNUS 2011), Aussois, France, 8-10 June 2011

Objective: To investigate the effect of Composite Divitriol Infusion (CDI) in treating tinea manum and study its antimycotic action.Methods: CDI was used to treat 139 patients with tinea manum and compared with Tinea Unguium Infusion in treating 77 cases as control. The experimental study in vivo was done, and electron microscopy (EM) was used to observe the therapeutical effect of CDI.Results: Among the 139 patients of the CDI group, 104 were cured, 21 markedly effective, 10 improved and 4 ineffective, the cure and markedly effective rate being 89.9%. The difference of effect between the CDI group and the control group was significant statistically (X2>12.84,P < 0.005). The antimycotic action of CDI was studied in vitro. The minimum inhibitory concentration (MIC) of CDI were about 0.25% for Trichophyton rubrum and 0.5% for Trichophyton gypseum and Microsporum gypseum. Trichophyton rubrum immersed with CDI showed that the mycelia became roughened, deformed, and macroconidium became smaller under EM.Conclusion: CDI is valuable in treating tinea manum.

Objective To explore p73 mRNA and p73 protein expression and their clinical significance in colorectal cancer. Method p73 mRNA and p73 protein expression were detected using hybridization in situ and immunohistochemical method in cancerous tissue from 60 patients of colorectal cancer and in paracancerous tissue from 23 patients among the corresponding 60 patients of colorectal cancer. Quantitative analysis was performed using Smartscape image analysis system. Results Compared with paracancerous tissue, p73 mRNA and p73 protein expression in cancerous tissue was increased with a statistically significant difference (P

For an engineering project with running income, the result of time-cost trade-off problems (TCTP) concerning construction duration is only partly optimal. More cash flow happens during the running period, and the final goal of clients is to obtain the maximal profit across the lifecycle of engineering projects. In some situations, the cost of compressing construction duration even exceeds the increase of income of running period. Therefore, there should be an optimal scheme with the whole profit maximum. The relationship between the income of running period and the construction duration is analyzed in this paper; with the time value of capital taken into account, the mathematic model of TCTP across the running period is developed. Furthermore, the improved genetic algorithms (GA) proposed in this paper are applied to optimize the model. In the end, an example is given to testify the validity of the TCTP across the running period with the time value of capital considered.

An all silicon-based on-chip optical interconnect is a promising candidate to overcome the electrical interconnect bottleneck. In this study, we focus on two missing optical building blocks: light sources and modulators. One- and two-dimensional photonic bandgap modulators are demonstrated. Light amplification is achieved in silicon nanocrystals and a distributed Bragg reflector is fabricated and tested to explore the possibility of a silicon laser.

Aim: The aim was to investigate the validity of sonometry on the assessment of gastric volumes in comparison with gastric barostat. Method: Six dogs were implanted with gastric serosal electrodes, sonometric sensors, and a gastric cannula. Experiments were performed to assess sensor distance when an intragastric balloon was inflated with different volumes, after a meal with or without a balloon, and with gastric electrical stimulation. Results: (i) The distance measured using sonometry was reproducible and stable, and there was a correlation between sensor distance and the gastric volume measured with barostat. (ii) Simultaneous recordings by sonometry and barostat showed a similar postprandial response, while the postprandial increase of the sensor distance was much smaller without the balloon (3.2 ± 0.2 mm vs 9.7 ± 1.5 mm, P

A novel PECVD porous low-k material with k=2.5, LK(k=2.5), has been successfully integrated with Cu for 90 nm generation BEOL interconnect technology on 300 mm wafers. Fundamental film studies showed that this low-k material is thermally stable up to 400/spl deg/C and can be strongly adhered to various dielectric films. Electrical measurement results from the Cu/LK(k=2.5) damascene interconnect showed tight and 100%-yielded distributions in 0.12/0.12 /spl mu/m interline leakage, one million 0.13 /spl mu/m viachain via Rc and 0.12 /spl mu/m Cu line Rs. To maximize the Cu/LK(k=2.5) interconnect capacitance performance, no middle etch stop layer and no top CMP cap were used in the dielectric film stacking. The final k value of the LK(k=2.5) after integration was retained at 2.5 using an optimized PR ashing chemistry by comparing the Cu/LK(2.5) 0.12/0.12 /spl mu/m interline capacitance to a Cu/LK(3.0) one. The intrinsic BEOL time dependent dielectric breakdown (TDDB) lifetime, T/sub 63,/ of the Cu/LK(k=2.5) is predicted to be 4.56/spl times/10/sup 8/ yrs at 0.3 MV/cm and 125/spl deg/C. Further reliability evaluations of the Cu/LK(k=2.5) in electromigration (EM) and stress migration (SM) showed that its predicted T/sub 0.1/ EM lifetimes for 0.12 /spl mu/m Cu line or 0.13 /spl mu/m via at 1 MA/cm2 and 110/spl deg/C are 152k hrs or 144k hrs, and its SM failure rate (>10% shift in Rc) is zero after 500hr annealing at 175/spl deg/C. Finally, the packaging feasibility of this Cu/LK(k=2.5) damascene interconnect was also demonstrated using current wire bonding technologies.