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Aims The coronavirus disease 2019 (COVID-19) pandemic represents an unprecedented threat to mental health. Herein, we assessed the impact of COVID-19 on subthreshold depressive symptoms and identified potential mitigating factors. Methods Participants were from Depression Cohort in China (ChiCTR registry number 1900022145). Adults (n = 1722) with subthreshold depressive symptoms were enrolled between March and October 2019 in a 6-month, community-based interventional study that aimed to prevent clinical depression using psychoeducation. A total of 1506 participants completed the study in Shenzhen, China: 726 participants, who completed the study between March 2019 and January 2020 (i.e. before COVID-19), comprised the ‘wave 1’ group; 780 participants, who were enrolled before COVID-19 and completed the 6-month endpoint assessment during COVID-19, comprised ‘wave 2’. Symptoms of depression, anxiety and insomnia were assessed at baseline and endpoint (i.e. 6-month follow-up) using the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI), respectively. Measures of resilience and regular exercise were assessed at baseline. We compared the mental health outcomes between wave 1 and wave 2 groups. We additionally investigated how mental health outcomes changed across disparate stages of the COVID-19 pandemic in China, i.e. peak (7–13 February), post-peak (14–27 February), remission plateau (28 February−present). Results COVID-19 increased the risk for three mental outcomes: (1) depression (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.04–1.62); (2) anxiety (OR = 1.47, 95% CI: 1.16–1.88) and (3) insomnia (OR = 1.37, 95% CI: 1.07–1.77). The highest proportion of probable depression and anxiety was observed post-peak, with 52.9% and 41.4%, respectively. Greater baseline resilience scores had a protective effect on the three main outcomes (depression: OR = 0.26, 95% CI: 0.19–0.37; anxiety: OR = 1.22, 95% CI: 0.14–0.33 and insomnia: OR = 0.18, 95% CI: 0.11–0.28). Furthermore, regular physical activity mitigated the risk for depression (OR = 0.79, 95% CI: 0.79–0.99). Conclusions The COVID-19 pandemic exerted a highly significant and negative impact on symptoms of depression, anxiety and insomnia. Mental health outcomes fluctuated as a function of the duration of the pandemic and were alleviated to some extent with the observed decline in community-based transmission. Augmenting resiliency and regular exercise provide an opportunity to mitigate the risk for mental health symptoms during this severe public health crisis.

BACKGROUND The short-term effect of ambient air pollution on atopic dermatitis (AD), along with its effect modifiers, has not been fully addressed. OBJECTIVES To examine the short-term associations between air pollution and AD, and to identify effect modifications by age and season. METHODS We used the generalized additive model to evaluate the short-term effect of ambient air pollution on daily hospital visits for AD, adjusting for potential confounders. Subgroup analyses were performed to identify potential effect modifications by season and age (< 18 years and ≥ 18 years). RESULTS A total of 29 972 hospital visits for AD were recorded in Guangzhou, China, from 19 January 2013 to 31 December 2017. Among them, 72·8% were visits by children and 51·4% occurred in the cool season. Acute and delayed effects on AD hospital visits were significant for all air pollutants. Stronger effects were seen in the cool season (approximately 1·7-3·0 times higher than effects in the warm season). Stronger effects were also observed in children (approximately 1·3-1·8 times higher than effects in adults). Sensitivity analyses indicated the results were robust. CONCLUSIONS Air pollution might be an important trigger for AD in subtropical Guangzhou, China. Children are more vulnerable than adults, and the effects are stronger in the cool season.

Background:The once daily, oral Janus kinase (JAK)-1 preferential inhibitor filgotinib (FIL) improved signs and symptoms of rheumatoid arthritis (RA) in phase (P)3 trials.1-3 Patients (pts) with RA have increased herpes zoster (HZ) reactivation risk vs the general population. JAK inhibition is associated with increased infection incidence, including HZ.4Objectives:To assess long-term safety of FIL across the global clinical program with respect to HZ.Methods:Pts meeting 2010 ACR/EULAR RA criteria in a pooled analysis of P2 DARWIN 1–2 (D1–2), P3 FINCH 1–3 (F1–3), and long-term extension studies (D3, F4) were included. Placebo (PBO)-controlled as-randomised analysis included pts receiving FIL 100 mg (FIL100), FIL 200 mg (FIL200), or PBO up to week (W)12 (D1–2, F1–2); active-controlled as-randomised analysis included pts receiving FIL100, FIL200, adalimumab (ADA), or methotrexate (MTX) up to W52 (F1, F3). Long-term as-treated analysis included pts in all 7 studies receiving FIL100, FIL200, ADA, MTX, or PBO; data after re-randomisation were included and contributed to treatment received. Exposure-adjusted incidence rates (EAIR)/100 patient-years, calculated up to the last follow-up time or day, and differences with 95% confidence intervals (CIs) were calculated from the Poisson model. Logistic regression model was used for treatment-emergent (TE) HZ risk factor analysis and odds ratio (95% CI) and P value were provided.Results:Table 1 shows TE HZ EAIRs in a pooled analysis. Rates of HZ were lower for FIL200 vs PBO during the 12W PBO-controlled period. At 52W, HZ rates were higher for FIL200/100 vs active control. Long-term HZ rates increased for FIL200 vs FIL100.Table 1.EAIR of treatment-emergent herpes zosterNPatient-years exposureEAIR(95% CI)EAIR diff(95% CI vs PBO/active control)12W PBO-controlled FIL200777179.80.6 (0.1, 3.9)−0.56 (−2.5, 1.3) FIL100788181.61.1 (0.3, 4.4)−0.02 (−2.2, 2.2) PBO781178.41.1 (0.3, 4.5)Active-controlled, as-randomiseda FIL200475439.71.4 (0.6, 3.0)0.69 (−0.7, 2.1) FIL100480443.40.9 (0.3, 2.4)0.23 (−1.1, 1.5) ADA325297.60.7 (0.2, 2.7)Active-controlled, as-randomiseda FIL200626578.01.7 (0.9, 3.2)0.65 (−0.8, 2.2) FIL100207195.01.5 (0.5, 4.8)0.46 (−1.6, 2.5) MTX416372.21.1 (0.4, 2.9)Long-term as-treatedb FIL20022674047.71.8 (1.4, 2.3)NC FIL10016472032.91.1 (0.8, 1.7)NCaup to W52. bdata cut for LTE FINCH 4, Sept 19, 2019; DARWIN 3, April 26 2019.ADA, adalimumab; CI, confidence interval; EAIR, exposure-adjusted incidence rate; FIL, filgotinib; MTX, methotrexate; NC, not calculated; PBO, placebo; W week.Figure 1 shows multivariate logistic regression model of TE risk factors.Of 104 pts with TE HZ in long-term as-treated analysis set, 5 receiving FIL200 had history of HZ; EAIR (95% CI) was 8.7 (3.6–21.0). Of 8 pts with multiple events, 3 had events of differing severity for the same HZ episode.EAIRs (95% CI) of TE HZ in Asia were: 3.7 (1.7–8.1) FIL200, n=197; 2.8 (1.3–6.3) FIL100, n=158; 0 ADA, n=40; 2.8 (0.4–19.6) MTX, n=43; and 3.4 (0.5–23.8) PBO, n=77 in long-term as-treated population. EAIRs (95% CI) in rest of the world were: 1.6 (1.2–2.1) FIL200, n=2070; 0.9 (0.6–1.5) FIL100, n=1489; 0.8 (0.2–3.1) ADA, n=285; 0.9 (0.3–2.9) MTX, n=373; and 0.7 (0.2–2.9) PBO, n=704 for all pts as-treated.Most TE HZ infections were mild to moderate and non-serious; 6 were serious; 2 were recurrences. No visceral TE HZ occurred across the FIL RA program; there was 1 case each of genital, disseminated, and ophthalmic HZ. The disseminated HZ occurred in a pt with prior HZ history. Lymphopenia was not associated with HZ during the PBO-controlled W12 period.Conclusion:HZ was more common in both FIL groups vs ADA or MTX up to 52 weeks but comparable vs PBO during the 12-week placebo-controlled period. In multivariate analyses, prior history of HZ, Asian region, and age ≥50 years were associated with increased HZ risk.References:[1]Genovese et al. JAMA. 2019;322:315–25.[2]Westhovens et al. Ann Rheum Dis. 2021; online first.[3]Combe et al. Ann Rheum Dis. 2021; online first.[4]Higarashi and Honda. Drugs. 2020;80:1183–201.Disclosure of Interests:Kevin Winthrop Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly and Co., Galapagos NV, Gilead Sciences, GlaxoSmithKline, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, and Pfizer, Maya H Buch Speakers bureau: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Grant/research support from: AbbVie; Eli Lilly and Company; Gilead Sciences, Inc.; Merck-Serono; Pfizer; Roche; Sandoz; Sanofi; and UCB, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB, Gerd Rüdiger Burmester Speakers bureau: AbbVie; Eli Lilly; Pfizer; and Gilead Sciences, Inc., Consultant of: AbbVie; Eli Lilly; Pfizer; and Gilead Sciences, Inc., Daniel Aletaha Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Medac, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi/Genzyme, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, and Sanofi/Genzyme, Grant/research support from: AbbVie, Merck Sharp & Dohme, Novartis, and Roche, Koichi Amano Speakers bureau: AbbVie GK, Astellas, Chugai Pharmaceutical Co. Ltd., Eli Lilly, GlaxoSmithKline KK, Pfizer Japan, Mitsubishi-Tanabe Pharma, Grant/research support from: Asahi Kasei Pharma, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Iyabode Tiamiyu Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Cianna Leatherwood Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Lei Ye Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Qi Gong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, BV, Employee of: Galapagos, BV, James Galloway Speakers bureau: Pfizer, Bristol-Myers Squibb, UCB and Celgene

Background:Filgotinib is an orally administered small molecule that preferentially inhibits Janus kinase 1 and is approved for use in Europe and Japan in adult patients with rheumatoid arthritis (RA) who have had an inadequate response to conventional therapies. Patients with RA are at a higher risk of cardiovascular morbidity and mortality relative to the general population1. Thus, it is important to understand potential drug-drug interactions of filgotinib with lipid-lowering agents such as statins. Based on in vitro studies, filgotinib is not expected to significantly increase exposure of statins via inhibition of the organic anion transporting peptide (OATP) at clinically relevant exposures. Hence, in Phase 2 and Phase 3 clinical studies, statins were allowed for use with filgotinib. A post-hoc analysis showed no increase in statin-induced AEs such as muscle or liver toxicities when statins were coadministered with filgotinib (“Concomitant Use of Statins in Filgotinib-Treated Patients with Rheumatoid Arthritis: A Post Hoc Analysis”, submitted to EULAR 2021).Objectives:The objectives of this study (NCT04608344) were to evaluate the effect of filgotinib on the pharmacokinetics of atorvastatin, pravastatin, and rosuvastatin, which are sensitive substrates for the OATP-1B1/1B3, and the short-term safety of administering filgotinib with or without statins.Methods:This was an open-label, randomized, two-way, crossover study in healthy adult volunteers (n = 27). Study participants received a single dose of atorvastatin (ATV 40 mg) and a single dose of a cocktail of pravastatin (PRA 40 mg)/rosuvastatin (ROS 10 mg), on two different occasions with washout in between, alone or in combination with filgotinib (200 mg QD for 11 days). Serial pharmacokinetic sampling was performed and pharmacokinetic parameters for each statin were calculated. Safety was assessed throughout the study. An analysis of variance using a mixed-effects model was applied to the natural logarithmic transformation of pharmacokinetic parameters (Cmax and AUCinf) for ATV, 2-OH-ATV (active metabolite of ATV), PRA, and ROS. Geometric-least squares means (GLSM) ratios and 90% confidence intervals (90% CI) of pharmacokinetic parameters were estimated for each analyte and were compared against pre-specified lack of pharmacokinetic alteration boundaries of 70 to 143%.Results:Of the 27 enrolled participants, 25 participants completed all study treatments. Most AEs and laboratory abnormalities were Grade 1 or 2 in severity; 1 participant discontinued due to a Grade 3 increase in creatine kinase and 1 participant discontinued due to difficulty in blood draws. Following coadministration of filgotinib with ATV, relative to ATV alone, ATV AUCinf was unaffected (GLSM ratio (90% CI): 0.91 (0.84, 0.99)), but ATV Cmax was slightly reduced (GLSM ratio (90% CI): 0.82 (0.69, 0.98)). 2-OH-ATV exposure (Cmax and AUCinf) were unaffected (GLSM ratio (90% CI): 0.98 (0.81, 1.18) for Cmax and 1.12 (1.02, 1.22) for AUCinf), and were within the pre-specified lack-of-effect bounds. Following coadministration with filgotinib, PRA AUCinf was unaffected (GLSM ratio (90% CI): 1.22 (1.06, 1.42)), but PRA Cmax was slightly higher (1.25 (1.01, 1.54)). ROS exposure (Cmax and AUCinf) were moderately higher upon coadministration with filgotinib (GLSM ratio (90% CI): 1.68 (1.43, 1.97) for Cmax and 1.42 (1.30, 1.56) for AUCinf), and these changes in rosuvastatin exposure are not considered to be clinically relevant.Conclusion:All study treatments were generally well tolerated. Co-administration with filgotinib did not have a clinically meaningful impact on the exposure of ATV, PRA, and ROS. These data support concomitant use of filgotinib with OATP substrates such as statins.References:[1]Piepoli MF, Hoes AW, Agewall S, et al. Eur Heart J. 2016;37(29): 2315-2381.Disclosure of Interests:Kacey Anderson Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Cara Nelson Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Qi Gong Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Thomas Tarnowski Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Ahmed A. Othman Shareholder of: Gilead Sciences, Employee of: Gilead Sciences

Purpose To quantitatively determine the size and contractility of the superior oblique (SO) muscle in primary SO overaction (PSOOA). Patients and methods A prospective, observational study was conducted on 12 patients with PSOOA, and 10 healthy, orthotropic subjects. Sets of contiguous, 2 mm slice thickness, quasi-coronal magnetic resonance imaging were obtained during different gazes, giving pixel resolution of 0.391 mm. Cross-sectional areas of the SO muscles were determined in primary position, supraduction, and infraduction to evaluate size and contractility. The cross-sectional areas of SO muscle were compared with those of controls in the primary position to detect hypertrophy or atrophy and changes in contractility could be detected during the vertical gaze. All statistical calculations were performed using PROC MIXED (SAS 9.4). Results There was no difference between the ipsilesional (affected eye), contralesional (unaffected eye), and normal SO muscle cross-sections: 0.176±0.018 cm2, 0.175±0.005 cm2, and 0.173±0.015 cm2, respectively (P=0.82). The maximum contractility of SO muscle on the ipsilesional (affected) side was 0.097±0.024 cm2, and was different than on the contralesional (unaffected) side: 0.067±0.015 cm2 and in control subjects: 0.063±0.018 cm2 (P=0.0002). Conclusions In PSOOA, the ipsilesional SO is more contractile than the contralesional SO muscle and different than in controls, with no difference in SO muscle size in primary position, which suggests that excessive innervation rather than muscle hypertrophy underlies PSOOA.

Identifying railway public interest transportation correctly is not only the requirement to ensure the healthy development of railway industry, but also the requirement for government to manage the public transport activities efficiently. Firstly, based on the analysis of the deification of railway public interest and railway public interest transportation, this paper summarizes the features of railway public interest; then through the analysis on the user benefit, supplier benefit and environmental improvement benefits, the identification method of railway public interest transportation is studied based on national economic benefits method, at last, this method is validated through the Golmud-Lhasa section of Qinghai-Tibet Railway.

The stop-signal paradigm is a widely used procedure to study response inhibition. It consists of a 2-choice response-time task (a "go" task) that is occasionally interrupted by a stop signal instructing participants to withhold their responses. The paradigm owes its popularity to the underlying race model that enables estimation of the otherwise unobservable latency of stopping. As the race model assumes a single go runner that produces the response unless it is beaten by an inhibitory stop runner, it cannot account for errors on the go task. We propose a parametric framework that extends the standard 2-runner race model to account for go errors, and hence expand the scope of the stop-signal paradigm to the study of response inhibition in the context of difficult choices. We combine our treatment of go errors with the ability to address 2 common contaminants in stop-signal data: failure to trigger the go or the stop runner. We show with simulations that applying 2-runner parametric race models to difficult choices can severely bias conclusions about response inhibition. Notably, we also show that even infrequent errors, which have been common in previous stop-signal studies, can result in underestimation of stopping latencies. We demonstrate that our framework enables researchers to study difficult-choice inhibition even in relatively small samples by applying it to novel stop-signal data with high error rates and a manipulation of task difficulty, showing that it provides an accurate characterization of behavior and precise stop estimates. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

To improve the availability of the software-defined networking (SDN) under distributed denial of service (DDoS) attacks, a multi-queue SDN controller scheduling algorithm based on time slice allocation strategy is proposed. The proposed algorithm can take different time slice allocation strategies according to the intensity of DDoS attacks and use SDN controller to schedule processing flow request from different switches (including the switches suffering from different degrees of attacks and normal switches) to ensure better protection to the normal switch in the network under DDoS attacks. Simulation results are presented to show the effectiveness of the proposed algorithm.

This study investigates supply chain cooperative management problem. In this study, based on principal-agent, firstly we analyses cooperative management factors in supply chain including leading enterprise expected utilities, subsidiary enterprise expected incomes and leading enterprise agency cost, then the incentive contract model is constructed; Secondly the model is solved in the case of symmetric information and asymmetric information; At last, in order to make clear of the model, this paper does mathematical analysis of leading enterprise expected utilities, subsidiary enterprise expected incomes and leading enterprise agency cost. Some important conclusions are obtained: subsidiary enterprise ability, cost coefficient, absolute risk aversion factor and output variance has the same influence on leading enterprise expected utilities and subsidiary enterprise expected incomes; subsidiary enterprise ability, cost coefficient has the same influence on leading enterprise expected utilities, subsidiary enterprise expected incomes and leading enterprise agency cost; leading enterprise expected utilities and subsidiary enterprise expected incomes become bigger and bigger, but leading enterprise agency cost becomes smaller and smaller with absolute risk aversion factor and output variance decreased. etc. Leading enterprise can take on incentive measures (improving subsidiary enterprise ability, decreasing subsidiary enterprise cost coefficient.etc) to optimize supply chain management based on the common factors.

Biomaterials are likely critical, if not indispensible, for dental pulp regeneration. This chapter presents up-to-date and critical information of biomaterials selection for dental pulp regeneration and is written for students, fellows, scientists, clinicians and government officials seeking better understanding of the scientific basis and therapeutic potential of dental pulp regeneration. Key challenges of dental pulp regeneration are discussed as well as biomaterial selection and strategies. Progress has been made to regenerate dental pulp-like tissues with both cell delivery and cell homing approaches. In tissue engineering and regeneration, the scale of the tissues to be regenerated is among some of the most critical factors for success. Due to its small scale, dental pulp regeneration represents one of the lower hanging fruits in the regeneration of all tissues and organs.

Neurological deficit following cerebral infarction correlates with not only primary injury, but also secondary neuronal apoptosis in remote loci connected to the infarction. Netrin-1 is crucial for axonal guidance by interacting with its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 5H (UNC5H). DCC and UNC5H are also dependence receptors inducing cell apoptosis when unbound by netrin-1. The present study is to investigate the role of netrin-1 and its receptors in ipsilateral ventroposterior thalamic nucleus (VPN) injury secondary to stroke in hypertensive rats. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO). Continuous intracerebroventricular infusion of netrin-1 (600 ng/d for 7 days) or vehicle (IgG/Fc) was given 24h after MCAO. Neurological function was evaluated by postural reflex 8 and 14 days after MCAO. Then, immunoreactivity was determined in the ipsilateral VPN for NeuN, glial fibrillary acidic protein, netrin-1 and its receptors (DCC and UNC5H2), apoptosis was detected with Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay, and the expressions of caspase-3, netrin-1, DCC, and UNC5H2 were quantified by western blot analysis. MCAO resulted in the impaired postural reflex after 8 and 14 days, with decreased NeuN marked neurons and increased TUNEL-positive cells, as well as an up-regulation in the levels of cleaved caspase-3 and UNC5H2 protein in the ipsilateral VPN, without significant change in DCC or netrin-1 expression. By exogenous netrin-1 infusion, the number of neurons was increased in the ipsilateral VPN, and both TUNEL-positive cell number and caspase-3 protein level were reduced, while UNC5H2 expression remained unaffected, simultaneously, the impairment of postural reflex was improved. Taken together, the present study indicates that exogenous netrin-1 could rescue neuron loss by attenuating secondary apoptosis in the ipsilateral VPN after focal cerebral infarction, possibly via its receptor UNC5H2, suggesting that relative insufficiency of endogenous netrin-1 be an underlying mechanism of secondary injury in the VPN post stroke.

A novel compact multiple-input multiple-output (MIMO) antenna using a ring hybrid is proposed in this paper. The proposed antenna is designed for the 2.4 GHz Wireless Local Area Network (WLAN) applications. A ring hybrid of arbitrary power division is designed as the orthogonal feeding network to improve the isolation between the ports of the two monopoles. Two meander-line monopoles are used to miniature the proposed antenna. The prototype antennas have been evaluated and compared through the scattering parameters, radiation patterns. The results show that the isolation between the ports of the proposed antenna is better than 23 dB with matched ports at 2.4 GHz. The size of the proposed antenna has also been reduced by 15.7%. The proposed antenna offers reasonable WLAN performances that make it suitable for MIMO applications.

Squeezing in the resonance fluorescence emitted by a regular structure of atoms is discussed. Intense squeezed light fields are a prerequisite, e.g., for efficient measurements with sensitivity below the standard quantum limit. Regular structures are known to offer macroscopic squeezed light due to the fixed phase relation between the light scattered by the respective atoms, but typically restrict squeezing to low incident light intensity. As our main result, we demonstrate that this restriction to low driving field intensity can be circumvented. For this, we assume a suitable modification of the surrounding electromagnetic bath, as it can be achieved, e.g., with a cavity. The modified environment leads to a redistribution of the collective dressed state populations, such that squeezing is recovered at strong driving. In such modified environments, squeezing even occurs for a resonant driving field, in contrast to the regular vacuum case.

A size effect has been revealed in the spectra of the second harmonic generated in a reflection from an amorphous silicon composite layer with inclusions of crystalline silicon (nanocrystallites) measured at room temperature: a decrease in the mean size of the nanocrystallites from 100 to 30 nm is accompanied by a shift of the spectral peak near 3.3 eV by 0.12 eV towards the short wavelengths and an increase in the peak width by a factor of 1.5. As a possible mechanism of this phenomenon, the effect of the structural defects on the parameters of the optical transitions in the nanocrystallites is discussed.

Summary Aim: To compare the 2-h postprandial blood glucose (PPBG) excursion following a standard test meal in insulin-requiring patients with diabetes treated twice daily with human insulin mix 50 vs. insulin lispro mix 50 (LM50). Methods: This was a multicentre, randomised, open-label, crossover comparison of two insulin treatments for two 12-week treatment periods in 120 Chinese patients. One- and 2-h PPBG and excursion values were obtained following a standardised test meal. Fasting blood glucose (FBG), haemoglobin A1c (HbA1c), insulin dose, rate of hypoglycaemia and safety data were obtained. A crossover analysis using SAS Proc MIXED was employed. Results: Mean 2-h PPBG excursion decreased from 6.32 ± 3.07 mmol/l at baseline to 3.47 ± 2.97 mmol/l at end-point in the LM50 group, and from 6.31 ± 2.88 at baseline to 5.02 ± 3.32 mmol/l at end-point in the human insulin mix 50 group (p

A planar ultra-wideband (UWB) bandpass filter with widened upper stopband is presented in this paper. The filter is constructed by adopting a novel simplified composite right-/left-handed (SCRLH) transmission line (TL) structure. The fundamental characteristics of the SCRLH TL are first analyzed, and then its corresponding microstrip implementation is utilized to realize the practical UWB bandpass filter. However, thanks to the inherent parasitic effects of the microstrip quasi-lumped elements at high frequency, a spurious passband comes into being around 15.1 GHz. With an aim to broaden the bandwidth of the upper stopband, two embedded open-circuited stubs are introduced in the input and output feeding lines, which can effectively suppress the spurious passband, thus generating a widened upper stopband.

In this paper, the studies of the Joule heating and its effects on electrokinetic transport (i.e., electroosmotic flow and electrophoretic transport) of solutes in rectangular microchannels are reported. 3D mathematical models describing the Joule heating induced temperature field and its effects on the EOF and electrophoretic transport of solutes in microchannels are developed, and the coupled governing equations are solved numerically using the finite volume based CFD technique. In addition, experiments are carried out to investigate the Joule heating associated phenomena and to verify the numerical models. A Rhodamine B based thermometry technique was employed to measure the solution temperature distributions in PDMS microfluidic channels. The micro particle image velocimetry (micro-PIV) technique was used to measure the velocity profiles of the EOF under the influence of Joule heating. The numerical solutions were compared with experimental results, and reasonable agreement was found. Both the numerical simulations and the experimental results show that the presence of the Joule heating causes the EOF velocity to deviate from its normal “plug-like” profile; moreover, the numerical simulations show that Joule heating not only accelerates the sample transport but also distorts the shape of the sample band. The simulation results also reveal that the Joule heating and its effects in a PDMS/PDMS channel is more significant than those in a glass/PDMS channel.

Two patients presenting with subcutaneous nodules, plaques, papules and ulceration caused by Trichophyton rubrum are described in this report. The first case was a 46-year-old woman referred with erythema and desquamation over her trunk, hands and feet for 30 years, progressing to nodules and ulceration over her trunk, arms and scalp for the last 2 years. The second case was a 34-year-old man who presented with a 2-year-history of itchy, erythema and desquamation over the trunk, progressing to papules, nodules and cyst around his ear, on the neck and scalp for 1 year. The diagnoses were suspected after direct microscopical examinations of the discharge materials, which revealed the presence of hyaline hyphae. The histological examinations showed granulomatous inflammatory infiltrates with fungal elements in the dermis including epithelioid cells, giant cells, lymphocytes and eosinophils, and the periodic acid-Schiff stain showed hypha within the granulomas. Cultures of puncture materials, skin biopsies and nails confirmed the diagnosis identifying T. rubrum. Antifungal therapies with itraconazole were successful in both patients, the lesions were completely clear with atrophic scars after 3 months. Side effects were not noticed during the medication. We discuss the clinical types of granulomatous cutaneous lesions caused by dermatophyte infections and evaluate the therapeutic effect of itraconazole.

In this paper, neural networks (NNs) and adaptive robust control design method are integrated to design a performance oriented control law with only output feedback for a class of single-input-single-output nth order nonlinear systems in a normal form. The nonlinearities in the system include repeatable unknown nonlinearities and nonrepeatable unknown nonlinearities such as external disturbances. In addition, unknown nonlinearities can exist in the control input channel as well. A high-gain observer is employed to estimate the states of system. All unknown but repeatable nonlinear functions are approximated by the outputs of multilayer neural networks with the estimated states as inputs to achieve a better model compensation. All NN weights are tuned on-line. In order to avoid possible divergence of on-line tuning, discontinuous projections with fictitious bounds are used in the weight adjusting law to make sure that all the weights are adapted within a prescribed range. Theoretically, the resulting controller achieves a guaranteed output tracking transient performance and a guaranteed final tracking accuracy in general. Certain robust control terms is then constructed to effectively attenuate various model uncertainties and estimate errors. Furthermore, if all the states are available and the unknown nonlinear functions are in the functional ranges of the neural networks, an asymptotic output tracking is also achieved to retain the perfect learning capability of NNs in the ideal situation provided that the ideal NN weights fall within the prescribed range. The output feedback neural network adaptive robust control is then applied to the control of a linear motor drive system. Experiments are carried out to show the effectiveness of the proposed algorithm and the excellent output tracking performance.

The purpose of this study was to evaluate risk factors for bone pain in patients receiving myelosuppressive chemotherapy and pegfilgrastim. Individual patient data from 22 pegfilgrastim clinical trials were analyzed. Multivariable logistic regression models were used to evaluate risk factors associated with grade ≥2 bone pain and any grade bone pain in the first chemotherapy cycle and across cycles 1–6. Of the 1949 patients analyzed, 19 and 36 % had grade ≥2 and any grade bone pain, respectively, in cycle 1, and 28 and 51 % had grade ≥2 and any grade bone pain, respectively, across cycles 1–6. In cycle 1, history of bone pain (odds ratio (OR), 1.51; 95 % confidence interval (CI), 1.09–2.07) was associated with increased risk of grade ≥2 bone pain; age ≥65 years (versus

In this paper, the recently proposed neural network adaptive robust control (NNARC) design axe generalized to synthesize performance oriented control laws for a class of nonlinear systems transformable to the semi-strict feedback forms through the incorporation of backstepping design techniques. All unknown but repeatable nonlinearities in system are approximated by outputs of multi-layer neural networks to achieve a better model compensation and an improved performance. Through the use of discontinuous projections with fictitious bounds, a controlled on-line training of all NN weights is achieved. Robust control terms can then be constructed to attenuate various model uncertainties effectively for a guaranteed output tracking transient performance and a guaranteed final tracking accuracy.

In this paper, neural networks (NNs) and adaptive robust control (ARC) design philosophy are integrated to design performance-oriented control laws for a class of single-input–single-output (SISO) nth-order non- linear systems. Both repeatable (or state dependent) unknown non-linearities and non-repeatable unknown non-linearities such as external disturbances are considered. In addition, unknown non-linearities can exist in the control input channel as well. All unknown but repeatable non-linear functions are approximated by outputs of multi-layer neural networks to achieve a better model compensation for an improved performance. All NN weights are tuned on-line with no prior training needed. In order to avoid the possible divergence of the on-line tuning of neural network, discontinuous projection method with fictitious bounds is used in the NN weight adjusting laws to make sure that all NN weights are tuned within a prescribed range. By doing so, even in the presence of approximation error and non-repeatable non-linearities such as disturbances, a controlled learning is achieved and the possible destabilizing effect of on-line tuning of NN weights is avoided. Certain robust control terms are constructed to attenuate various model uncertainties effectively for a guaranteed output tracking transient performance and a guaranteed final tracking accuracy in general. In addition, if the unknown repeatable model uncertainties are in the functional range of the neural networks and the ideal weights fall within the prescribed range, asymptotic output tracking is also achieved to retain the perfect learning capability of neural networks in the ideal situation. The proposed neural network adaptive control (NNARC) strategy is then applied to the precision motion control of a linear motor drive system to help to realize the high-performance potential of such a drive technology. NN is employed to compensate for the effects of the lumped unknown non-linearities due to the position dependent friction and electro-magnetic ripple forces. Comparative experiments verify the high-performance nature of the proposed NNARC. With an encoder resolution of 1 µm, for a low-speed back-and-forth movement, the position tracking error is kept within ±2 µm during the most execution time while the maximum tracking error during the entire run is kept within ±5.6 µm. Copyright © 2001 John Wiley & Sons, Ltd.

The Cellular Fixed Broadband Access System for LMCS (Local Multipoint Communication Services) is aiming to provide broadband services to fixed subscribers through wireless access. A representative LMCS scenario involves a cellular system design with the entire allocated bandwidth being used in each cell and with a highly directional antenna employed at the subscriber. The LMCS system designs rely on assumed information regarding radio propagation phenomena in the anticipated coverage areas. The research reported here, therefore, has the objective of verifying such information by theoretical modeling and simulation. Simulation and analysis have been used to study the effects of a number of factors on the system performance and interference characteristics of such a LMCS system. The investigated factors include beamwidth and gain ratio of directional antennas, sectorization of hub antennas, propagation exponent, lognormal shadowing, site diversity and transmitter power control. Both models of LOS (line of sight) and NLOS (non-line of sight) have been investigated in this work. The simulation results demonstrate that highly directional antennas at the subscribers can dramatically improve the system performance for both uplink and downlink. The system design with frequency reuse of one is examined, and it is confirmed that an outage of 0.9% for a NLOS system could be achieved by using narrow beam antennas of 3 degrees with site diversity and power control techniques employed. Under the condition of LOS available for the desired links, the outage can be expected to be as low as 0.3%.

Background and objectives Superficial fungal skin infections are treated using topical antifungals. The aim of this study was to demonstrate the efficacy of a single application of 1 % terbinafine film-forming solution (FFS) versus placebo for the treatment of tinea pedis in the Chinese population. Methods Six centers in China randomized 290 patients in a 1:1 ratio to receive either 1 % terbinafine FFS or FFS vehicle (placebo) once on the affected foot/feet. Efficacy assessments included microscopy and mycologic culture, and assessing clinical signs and symptoms at baseline, and at weeks 1 and 6 after the topical treatment. All adverse events were recorded. Results At week 6, 1 % terbinafine FFS was superior to placebo for effective treatment rate (63 vs. 8 %); clinical cure (30 vs. 6 %); mycological cure (86 vs. 12 %); negative microscopy (90 vs. 24 %); and negative mycological culture (90 vs. 27 %): all p ≤ 0.001 and clinically relevant. At week 6, 1 % terbinafine FFS was clinically superior to placebo for the absence of: erythema (69 vs. 29 %); desquamation (33 vs. 8 %); and pruritus (70 vs. 30 %): all p ≤ 0.001 and clinically relevant. At week 6, differences in the average total signs and symptoms scores were significantly lower for 1 % terbinafine FFS versus placebo (p ≤ 0.001). Both 1 % terbinafine FFS and placebo were safe and well tolerated based on adverse events and investigator and patient assessments. Conclusions This double-blind, randomized, multicenter study demonstrated one single topical application of 1 % terbinafine FFS was safe and effective in the treatment of tinea pedis in the Chinese population.

According to the theories of Traditional Chinese Medicine (TCM), all Chinese medicinal substances have a special nature (cold, hot, warm or cool). Processing of Chinese Materia Medica (Pao zhi) is usually applied to modify the nature of medicinal substances to meet clinical needs [1]. It is believed that, after processing by materials with different natures, such as wine (hot) or animal bile (cold), the cold nature of Coptidis Rhizoma (CR. Coptis chinensis Franch.) could be moderated to be less cold or reinforced to be even colder. This change may be monitored by energy metabolic parameters. To evaluate the effects of processing on a Chinese medicinal substance's nature, HPLC-MS/MS-based metabonomics was used to find the possible energy metabolism biomarkers of processed CR in rat urine. Sprague-Dawley (SD) rats were administrated 15g·kg-1 of an aqueous extract of wine-processed and bile-processed CR for 29 days. Urine was collected at different durations and analyzed by HPLC-MS/MS. The data were analyzed using principal component analysis (PCA) with SIMCA-P 1010 software. The metabonome showed the biggest difference in the 29th day between the groups treated by wine-processed and bile-processed CR. For both groups, 92 kinds of biomarkers were identified, among which 1, 3-bisphosphoglycerate, cis-aconitic acid and malic acid were consistent with previously observed pharmacological effects of energy metabolisms [2]. The concentrations of the energy metabolism markers were found to be lower in bile-processing group than those in wine-processing group, suggesting that bile-processed CR was more likely to decrease rats' energy metabolism than wine-processed CR. The goal of this research was to provide a better understanding of processing effects on the nature of Chinese medicinal substances. Acknowledgements: This research work is financially supported by Young Scientists training program in Jiangxi Province (Project No. 2007185). We thank Key Laboratory of Jiangxi University of TCM, Ministry of Education of China for the operation support for HPLC-MS/MS. References: [1] Wang XQ (1989), China Journal of Hospital Pharmacy, 9: 359–360. [2] Chen BB (2000), Lishizhen Medicine and Materia Medica Research, 11: 858–859.

Biomaterials are likely to be critical, if not indispensible, for dental pulp regeneration. This review presents up-to-date information about biomaterials selection for dental pulp regeneration with the intent to elucidate the scientific basis and therapeutic potential. Key challenges of dental pulp regeneration as well as biomaterial selection and strategies are discussed. Progress has been made to regenerate dental-pulp-like tissues by both cell delivery and cell-homing approaches. Due to its small scale, dental pulp regeneration represents one of the lower hanging fruits in the regeneration of all tissues and organs.

Aims/hypothesis We determined the effects of 6 years of lifestyle intervention in persons with impaired glucose tolerance (IGT) on the development of retinopathy, nephropathy and neuropathy over a 20 year period. Methods In 1986, 577 adults with IGT from 33 clinics in Da Qing, China were randomly assigned by clinic to a control group or one of three lifestyle intervention groups (diet, exercise, and diet plus exercise). Active intervention was carried out from 1986 to 1992. In 2006 we conducted a 20 year follow-up study of the original participants to compare the incidence of microvascular complications in the combined intervention group vs the control group. Results Follow-up information was obtained on 542 (94%) of the 577 original participants. The cumulative incidence of severe retinopathy was 9.2% in the combined intervention group and 16.2% in the control group (p = 0.03, log-rank test). After adjusting for clinic and age, the incidence of severe retinopathy was 47% lower in the intervention group than the control group (hazard rate ratio 0.53, 95% CI 0.29–0.99, p = 0.048). No significant differences were found in the incidence of severe nephropathy (hazard rate ratio 1.05, 95% CI 0.16–7.05, intervention vs control, p = 0.96) or in the prevalence of neuropathy (8.6% vs 9.1%, p = 0.89) among the 20 year survivors. Conclusions/interpretation Lifestyle intervention for 6 years in IGT was associated with a 47% reduction in the incidence of severe, vision-threatening retinopathy over a 20 year interval, primarily due to the reduced incidence of diabetes in the intervention group. However, similar benefits were not seen for nephropathy or neuropathy.

Herbal preparations are evolving as promising agents for the treatment of functional gastrointestinal disorders which are considered to be secondary to visceral hypersensitivity. We aimed to determine whether a new combination of six herbal extracts reduces the sensitivity of intestinal afferents in rat. Male Wistar rats (250-350 g, n = 6 per group) were gavaged with either vehicle or 2.5, 5 or 10 mL kg(-1) of STW 5-II, a herbal preparation which contains six extracts. Two hours later, animals were anaesthetized and extracellular multi-unit mesenteric afferent nerve recordings were obtained in the proximal jejunum in vivo. Afferent discharge to 5-hydroxy-tryptamine (5-HT) (5, 10, 20 and 40 microg kg(-1), i.v.), luminal distension (0-60 mmHg) and bradykinin (BK) (15, 30 and 60 microg kg(-1), i.v.) was recorded. At baseline, spontaneous afferent discharge was not different following pretreatment with the various doses of STW 5-II compared with vehicle. The pressure-dependent increase in afferent discharge to intraluminal ramp distension and the dose-dependent increase in afferent firing following 5-HT were also uninfluenced by STW 5-II pretreatment. In contrast, the afferent nerve responses to 15, 30 and 60 microg kg(-1) of BK were reduced following 10 mL kg(-1) STW 5-II with peaks at 106 +/- 19, 153 +/- 22 and 156 +/- 25 imp s(-1) compared with 160 +/- 15, 228 +/- 14 and 220 +/- 16 imp s(-1) following vehicle pretreatment (mean +/- SEM, P < 0.05). Intestinal afferent sensitivity to BK which plays a prime role in nociception was reduced following STW 5-II. Thus, STW 5-II may be of therapeutic use for conditions that involve neuronal hypersensitivity and the release of BK in the intestine.

We explored the effects of recombinant A-box (rA-box), a specific blockade for endogenous high mobility group box 1 (HMGB1) protein, on acute lung inflammation induced by lipopolysaccharide (LPS) in vivo. Acute lung injury (ALI) was produced successfully by intratracheal administration of LPS (10 microg/mouse) in male BALB/c mice. rA-box (0.3, 0.6 mg/mouse, i.p.) was administered 30 min prior to or 2 h after LPS exposure. Bronchoalveolar lavage fluid (BALF) was obtained to measure chemokines, proinflammatory cytokines, total cell counts and proteins at the indicated time points. It was found that rA-box caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and protein leakage at 24 h after LPS challenge. In addition, rA-box was also believed to have downregulated the expression of LPS-induced chemokines (keratinocyte-derived chemokine) and proinflammatory cytokines, including early mediator TNF-a and late mediator HMGB1. These findings confirm the significant protection of rA-box against LPS-induced ALI, and the effect mechanism of rA-box was associated with decreasing the expression of chemokines and proinflammatory cytokines.

Adsorbate-induced band gap states in semiconductors are of particular interest due to the potential of increased light absorption and photoreactivity. A combined theoretical and experimental (STM, photoemission) study of the molecular-scale factors involved in the formation of gap states in TiO(2) is presented. Using the organic catechol on rutile TiO(2)(110) as a model system, it is found that the bonding geometry strongly affects the molecular electronic structure. At saturation catechol forms an ordered 4 x 1 overlayer. This structure is attributed to catechol adsorbed on rows of surface Ti atoms with the molecular plane tilted from the surface normal in an alternating fashion. In the computed lowest-energy structure, one of the two terminal OH groups at each catechol dissociates and the O binds to a surface Ti atom in a monodentate configuration, whereas the other OH group forms an H-bond to the next catechol neighbor. Through proton exchange with the surface, this structure can easily transform into one where both OH groups dissociate and the catechol is bound to two surface Ti in a bidentate configuration. Only bidendate catechol introduces states in the band gap of TiO(2).

The systematical report presents our studies on the gecko that integrated biological fundaments for biomimetics – morphology, locomotive mechanics, neural signal decoding and adhesive mechanism that developed a gecko-inspired robot and gecko-robot. A 3 dimensional locomotion gait for a gecko moving on the floor, wall and ceiling was obtained by using one high speed camera recording and image processing. The effect of electric potential on the adhesion was studied. The gecko’s foot-toe, a 22 degree-of-freedom motion system, was modulated by stimulating the three neurons on the limb. A stereotaxis method was proposed and the instrument was developed. The brain atlas for the gecko was primarily set up. Based on biological understanding, a bio-inspired geckolike robot was developed and the characteristics of the mechanics were investigated. The robot’s gait and motion coordination was introduced from the three dimensional gait results. Locomotion of the gecko was modulated by implanting electrodes into the gecko’s middle brain and stimulating by a wireless controlling system.

We report the first successful growth of InGaPBi single crystals on InP substrate with Bi concentration far beyond the doping level by gas source molecular beam epitaxy. The InGaPBi thin films reveal excellent surface and structural qualities, making it a promising new III-V compound family member for heterostructures. The strain can be tuned between tensile and compressive by adjusting Ga and Bi compositions. The maximum achieved Bi concentration is 2.2 ± 0.4% confirmed by Rutherford backscattering spectroscopy. Room temperature photoluminescence shows strong and broad light emission at energy levels much smaller than the InP bandgap.

We present a detailed review of the calibration of the LASCO C3 coronagraph on the SOHO satellite. Most of the calibration has been in place since early in the mission and has been utilized to varying degrees as required by specific analysis efforts. However, using observational data from the nearly decade-long database of LASCO images, we have re-evaluated and improved many aspects of the calibration. This includes the photometric calibration, vignetting function, geometric distortion, stray light, and exposure and observation times. Using this comprehensive set of corrections we have generated and made available a set of calibrated coronal images along with a set of periodic background images to ease the accessibility and use of the LASCO database.

The space-born coronagraph is an instrument used to observe the solar corona, the outer atmosphere of the Sun, typically over a range of altitudes from close to the limb of the solar disk to tens of solar radii. The brightness of the solar disk is many orders of magnitude greater than that of the corona. A coronagraph is designed to reject the light from the solar disk such that the corona is observable. An externally-occulted coronagraph is basically a telescope that forms an image of the corona, with the addition of an external occulter before and an internal occulter after the objective elements and stops, positioned and sized to reject light from the solar disk. The main source of stray light is diffraction of solar light around the edge of the external occulter, which is then scattered into the image plane by the optical elements. The occulters and stops are designed to reduce the intensity of diffracted and scattered light in the coronagraph as much as possible. We have developed a numerical model of the diffraction by an external occulter system and validated the model experimentally. We used the model to optimize the external occulter design for the SECCHI COR2 instrument, which is part of the NASA STEREO mission. We also used the model for the GOES-R SCOR concept design to predict the sensitivity of the instrument to misalignment and off-pointing from the Sun. In this paper, we will present the results of this experimental and numerical study of the performance of the external occulters on these instruments.

Background: We previously demonstrated an essential role for lipopolysaccharide binding protein (LBP) in the pulmonary immune response to Gram-negative bacterial infection. LBP knockout mice had significantly higher mortality, greater rates of bacteremia, and higher counts of viable bacteria in their lungs at killing than did wild-type controls. We postulate that systemic LBP gene therapy will reconstitute a protective innate immune response in LBP knockout mice and that overexpression of LBP in wild-type mice may offer a survival advantage. Methods: Twelve-to 16-week-old female C57BL/6 wild-type mice and age-matched LBP knockout mice were given 5 × 109 plaque-forming units of recombinant adenovirus containing either the gene for LBP or the irrelevant control protein β-galactosidase by tail vein injection; 72 hours later; each mouse was administered 1 × 103 colony-forming units of Klebsiella pneumoniae by intratracheal injection. Results: Administration of LBP by systemic gene therapy to LBP knockout mice improved survival from Klebsiella pneumonia to a level equivalent to or better than that in wild-type mice exposed to the same dose of bacteria (36% versus 25%). Wild-type mice given the LBP gene therapy demonstrated increased 7-day survival from Klebsiella pneumonia when compared with controls treated with β-galactosidase (68% versus 30%; p = 0.03). Conclusion: Systemic gene therapy with intravenous adenoviral vector transfer of LBP significantly improves survival in LBP knockout mice. Overexpression of LBP in wild-type mice improves survival from Klebsiella pneumonia. Raising levels of LBP in the setting of Gram-negative pneumonia may be of therapeutic benefit.

Self-organized InAs quantum dots sheets are grown on an GaAs[100] substrate and capped by 80 nm GaAs layer with molecular beam epitaxy. Samples were annealed and characterized with Raman spectra, transmission electron microscopy (TEM) and photoluminescence (PL). The Raman spectra indicates arsenic clusters in the GaAs capping layer. The TEM analysis revealed the relaxation of strain in some InAs islands with the introduction of the network of 90/spl deg/ dislocations. In addition, the structural changes also lead to the changes of the PL spectra from the InAs islands. Their correlation was discussed. Our results suggest that annealing may be used to intentionally modify the properties of self-organized InAs islands on GaAs.

Quantum dot lasers are predicted to have proved lasing characteristics compared to quantum well and quantum wire lasers. We report on quantum dot lasers with active media of vertically stacked InAs quantum dot layers grown by molecular beam epitaxy. The laser diodes were fabricated and the threshold current density of 220 A/cm/sup 2/ was achieved at room temperature with lasing wavelength of 951 nm. The characteristic temperature T/sub 0/ was measured to be 333 K and 157 K for the temperature ranges of 40-180 K and 180-300 K, respectively.