Donor Allospecific CD44high Central Memory T Cells Have Decreased Ability to Mediate Graft-vs.-Host Disease

Data from both animal models and humans have demonstrated that effector memory T cells (TEM) and central memory T cells (TCM) from unprimed donors have decreased ability to induce graft-vs-host disease (GVHD). Allospecific TEM from primed donors do not mediate GVHD. However, the potential of alloreactive TCM to induce GVHD is not clear. In this study, we sought to answer this question using a novel GVHD model induced by T cell receptor (TCR) transgenic OT-II T cells. Separated from OT-II mice immunized with OVA protein 8 weeks earlier, the allospecific CD44high TCM were able to mediate skin graft rejection after transfer to naive mice, yet had dramatically decreased ability to induce GVHD. We also found that these allospecific CD44high TCM persisted in GVHD target organs for more than 30 days post-transplantation, while the expansion of these cells was dramatically decreased during GVHD, suggesting an anergic or exhausted state. These observations provide insights into how allospecific CD4+ TCM respond to alloantigen during GVHD and underscore the fundamental difference of alloresponses mediated by allospecific TCM in graft rejection and GVHD settings

Shaking table testing and numerical modeling of continuous welded ballast track on bridges under longitudinal seismic loading

In order to confirm the validity of the ideal elasto-plastic resistance model applied to the ballast track under seismic loading, this paper studies the seismic response of continuous welded ballast track on bridges through the shaking table test and presents a process of updating the model based on the test results. The results indicate that the track constraint can improve the low order natural frequency of bridges significantly, and reduce the displacement response of the bridge. When ballast beds are effectively in a dynamic reciprocating state while under seismic loading, a structural change between the granules will occur, wherein some will flow and redistribute. The dynamic hysteretic change of the ballast longitudinal resistance is complex and quite different from that of the ideal elasto-plastic hysteretic route, and the ballast longitudinal resistance performance degenerates. If ballast longitudinal resistance is assumed to be ideal elastic-plastic resistance, the actual beam displacement response will be underestimated and the calculated rail seismic force will be greater than the test result. Moreover, the equivalent stiffness coefficient Ke and damping coefficient Ce of the ballast dynamic resistance characteristics could be obtained by model updating, and the simulation results coincide well with the test results

Cost-effectiveness of dapagliflozin for patients with heart failure across the spectrum of ejection fraction:A pooled analysis of DAPA-HF and DELIVER data

Aim: To assess the cost-effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF). Methods and results: Patient-level data were pooled from HF trials (DAPA-HF, DELIVER) to generate a population including HF with reduced, mildly reduced and preserved LVEF, to increase statistical power and enable exploration of interactions among LVEF, renal function and N-terminal pro-B-type natriuretic peptide levels, as they are relevant determinants of health status in this population. Survival and HF recurrent event risk equations were derived and applied to a lifetime horizon Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire total symptom score quartiles; costs and utilities were in the UK setting. The base case incremental cost-effectiveness ratio (ICER) was £6470 per quality-adjusted life year (QALY) gained, well below the UK willingness-to-pay (WTP) threshold of £20 000/QALY gained. In interaction sensitivity analyses, the highest ICER was observed for elderly patients with preserved LVEF (£16 624/QALY gained), and ranged to a region of dominance (increased QALYs, decreased costs) for patients with poorer renal function and reduced/mildly reduced LVEF. Results across the patient characteristic interaction plane were mostly between £5000 and £10 000/QALY gained. Conclusions: Dapagliflozin plus usual care, versus usual care alone, yielded results well below the WTP threshold for the UK across a heterogeneous population of patients with HF including the full spectrum of LVEF, and is likely a cost-effective intervention.</p

Cost-effectiveness of dapagliflozin for patients with heart failure across the spectrum of ejection fraction:A pooled analysis of DAPA-HF and DELIVER data

Aim: To assess the cost-effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF). Methods and results: Patient-level data were pooled from HF trials (DAPA-HF, DELIVER) to generate a population including HF with reduced, mildly reduced and preserved LVEF, to increase statistical power and enable exploration of interactions among LVEF, renal function and N-terminal pro-B-type natriuretic peptide levels, as they are relevant determinants of health status in this population. Survival and HF recurrent event risk equations were derived and applied to a lifetime horizon Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire total symptom score quartiles; costs and utilities were in the UK setting. The base case incremental cost-effectiveness ratio (ICER) was £6470 per quality-adjusted life year (QALY) gained, well below the UK willingness-to-pay (WTP) threshold of £20 000/QALY gained. In interaction sensitivity analyses, the highest ICER was observed for elderly patients with preserved LVEF (£16 624/QALY gained), and ranged to a region of dominance (increased QALYs, decreased costs) for patients with poorer renal function and reduced/mildly reduced LVEF. Results across the patient characteristic interaction plane were mostly between £5000 and £10 000/QALY gained. Conclusions: Dapagliflozin plus usual care, versus usual care alone, yielded results well below the WTP threshold for the UK across a heterogeneous population of patients with HF including the full spectrum of LVEF, and is likely a cost-effective intervention.</p

High sulfur loading and shuttle inhibition of advanced sulfur cathode enabled by graphene network skin and N, P, F-doped mesoporous carbon interfaces for ultra-stable lithium sulfur battery

Achieving high loading of active sulfur yet rational regulating the shuttle effect of lithium polysulfide (LiPS) is of great significance in pursuit of high-performance lithium-sulfur (Li-S) battery. Herein, we develop a free-standing graphene-nitrogen (N), phosphorus (P) and fluorine (F) co-doped mesoporous carbon-sulfur (G-NPFMC-S) film, which was used as a binder-free cathode in Li-S battery. The developed mesoporous carbon (MC) achieved a high specific surface area of 921 m2·g–1 with a uniform pore size distribution of 15 nm. The inserted graphene network inside G-NPFMC-S cathode can effectively improve its electrical conductivity and simultaneously restrict the shuttle of LiPS. A high sulfur loading of 86% was achieved due to the excellent porous structures of graphene-NPFMC (G-NPFMC) composite. When implemented as a freestanding cathode in Li-S battery, this G-NPFMC-S achieved a high specific capacity (1,356 mAh·g–1), favorable rate capability, and long-term cycling stability up to 500 cycles with a minimum capacity fading rate of 0.025% per cycle, outperforming the corresponding performances of NPFMC-sulfur (NPFMC-S) and MC-sulfur (MC-S). These promising results can be ascribed to the featured structures that formed inside G-NPFMC-S film, as that highly porous NPFMC can provide sufficient storage space for the loading of sulfur, while, the N, P, F-doped carbonic interface and the inserted graphene network help hinder the shuttle of LiPS via chemical adsorption and physical barrier effect. This proposed unique structure can provide a bright prospect in that high mass loading of active sulfur and restriction the shuttle of LiPS can be simultaneously achieved for Li-S battery

Prescription drug demand for psychotropics: The impact of out-of-pocket payment

This thesis examines the effect of out-of-pocket payment on the purchase of psychotropic drugs for treating depressive disorders. Using the Medical Expenditure Panel Survey (MEPS) data from 1996 to 2000, the numbers of psychotropic purchases among patients with depressive disorder in a time period are modeled using truncated count data models, with covariates that include the out-of-pocket payment and other measurements related to demographics, socioeconomic characteristics, and health status. Potential endogeneity of the out-of-pocket payment variable is handled with an instrumental variable approach. We find an overall out-of-pocket price elasticity of −0.225, suggesting that the demand for psychotropics is responsive to changes in out-of-pocket price, but the degree of responsiveness varies dramatically between depressed elderly and depressed non-elderly. Some degree of moral hazard is likely to be present among the young and the middle age, but not among the elderly, where demand is quite inelastic (−0.046). We also find evidence of plan manipulation, whereby insurers structure insurance plans to attract healthy subjects and/or repel unhealthy ones. In addition, we find evidence of undertreatment and poor adherence to treatment among depressive disorder patients.

Hand-foot-mouth disease and use of steroids, intravenous immunoglobulin, and traditional Chinese herbs in a tertiary hospital in Shantou, China

Abstract Background In contrast to the guidelines of World Health Organization (WHO) and United States-Centers for Disease Control and prevention (US-CDC), the Chinese national guidelines recommend the use of steroids, intravenous immunoglobulin (IVIG), or traditional Chinese herbs (TCHs) in hand-foot-mouth disease (HFMD) management. Their use and therapeutic efficacies are, however, unclear. We aimed to describe their use in and the clinical outcomes of hospitalized HFMD cases. Methods A retrospective review of hospital medical records for HFMD cases during 2008–2016 was conducted in a medical school-affiliated tertiary hospital in Shantou, Guangdong, China. Results Hospitalized children with the discharge diagnosis of HFMD (n = 3778), comprising mild (58.4%), severe (41.5%), and very severe (0.1%) cases, were enrolled in the study. Steroids, IVIG, and antiviral TCH Lan-Qin were respectively prescribed in 60.5, 37.1, and 71.0% of cases. Most cases (99.8%) recovered and six died. Recovery rate was lower with the use of IVIG and higher with Lan-Qin (alone or in combination with steroid) in the mild cases (Ps < 0.05). Longer hospital stay was observed with steroid/IVIG with or without Lan-Qin in the severe cases (Ps < 0.05). Conclusions This nine-year retrospective review shows 1) an increase in the incidence of HFMD as well as the use of steroids, IVIG, and TCH over time, 2) no significant advantage of using steroids and IVIG, either alone or in combination, in the management of mild HFMD cases, and 3) a higher recovery rate in mild HFMD cases with the use of antiviral TCH (Lan-Qin). Our findings need verification in a larger prospect study with cases from hospitals in other regions of China. Lan-Qin efficacy should be evaluated in randomized trials. Meanwhile, caution should be exercised in the extensive use of steroids and IVIG in HFMD management

The Study of the Knowledge Spillover pattern in China through patents in USPTO

本文通過研究美國專利局的中國專利，主要探討了以下兩個問題：1、哪些性質會影響專利的傳播；2、引證專利與被引證專利間有哪些關係。在數據方面，本文主要使用了2000 年至2012 年美國專利局發明人為中國的專利。通過分析其中G 類（物理類）和H 類（電學類）類專利是否有被其他專利引證，本文發現，專利權人、發明人所在地以及科技領域都會對專利是否會被引證造成影響，相比其他兩個因素，科技領域的影響不能被忽視。在專利權人方面，企業專利被引證的概率較高，政府和研究機構的專利被引證的概率較低，在企業方面，台灣、美國和其他國家的企業都較易被引證。在地理位置上，京津冀和長三角的專利都比珠三角的專利更易被引證，而中國境內其他地區的專利都更不易被引證在科技領域，G08 類（信號裝置類）、H01 類（基本電子元件）和H05 類(其他電氣技術)專利被引證的概率最高，H03（基本電子電路）類專利被引證概率最低。此外，一項專利引證其他專利的數量與和專利的年齡都與專利被引證的概率有正向關係。在引證專利和被引證專利的关系上本文發現，專利更傾向於引證與自己專利權人類型相同，地理區域接近，科技領域相似的專利This thesis studies the pattern of knowledge spillover in China based on patent citation. The data used are patents granted by USPTO to inventors based in China with the application year dated between 2000 and 2012. Only patents falling under the categories of G and H of the International Patent Classification, where the Chinese patents are concentrated, are investigated. The theme of study is: How patent citation is affected by the status of the patent owner (assignee), the location of the inventor, and the technology scope of the patent. The empirical results show that all three factors matter, but they are inter-related and their effects may overlap. In general, patents assigned to business firms are more likely to be cited compared to patents assigned to government and academic institutions, especially patents belong to non-Chinese companies, including those based in U.S., Taiwan, and other countries.Among different technological fields, patents in the categories of G08, H01, H05 are most likely to receive citations, while G01 and H03 are least likely. Patents invented in Greater Beijing area and Yangtze River Delta are more likely to be cited than patents invented in Pearl River Delta. Moreover, the probability to receive a citation is positively related to the number of citations of the original patent and the age of the patent. A patent is more likely to be cited by another patent owned by the same kind of assignees (business, academics, or institutions), invented in the same location, or falling in the same technology category, than otherwise

Comparison of different methods for total RNA extraction from sclerotia of Rhizoctonia solani

Background: Rhizoctonia solani (teleomorph: Thanatephorus cucumeris) is one of the most important pathogens of rice (Oryza sativa L.) that causes severe yield losses in all rice-growing regions. Sclerotia, formed from the aggregation of hyphae, are important structures in the life cycles of R. solani and contain a large quantity of polysaccharides, lipids, proteins and pigments. In order to extract high-quality total RNA from the sclerotia of R. solani, five methods, including E.Z.N.A.™ Fungal RNA Kit, sodium dodecyl sulfate (SDS)–sodium borate, SDS–polyvinylpyrrolidone (PVP), guanidinium thiocyanate (GTC) and modified Trizol, were compared in this study. Results: The electrophoresis results showed that it failed to extract total RNA from the sclerotia using modified Trizol method, whereas it could extract total RNA from the sclerotia using other four methods. Further experiments confirmed that the total RNA extracted using SDS–sodium borate, SDS–PVP and E.Z.N.A.™ Fungal RNA Kit methods could be used for RT-PCR of the specific amplification of GAPDH gene fragments, and that extracted using GTC method did not fulfill the requirement for above-mentioned RT-PCR experiment. Conclusion: It is concluded that SDS–sodium borate and SDS–PVP methods were the better ones for the extraction of high-quality total RNA that could be used for future gene cloning and expression studies, whereas E.Z.N.A.™ Fungal RNA Kit was not taken into consideration when deal with a large quantity of samples because it is expensive and relatively low yield

Analysis of the Interconnections between Classic Vortex Models of Coherent Structures Based on DNS Data

Low- and high-speed streaks (ejection, Q2, and sweep, Q4, events in quadrant analysis) are significant features of coherent structures in turbulent flow. Streak formation is closely related to turbulent structures in several vortex models, such as attached eddy models, streamwise vortex analysis models, and hairpin vortex models, which are all standard models. Vortex models are complex, whereby the relationships among the different vortex models are unclear; thus, further studies are still needed to complete our understanding of vortices. In this study, 30 sets of direct numerical simulation (DNS) data were obtained to analyze the mechanics of the formation of coherent structures. Image processing techniques and statistical analysis were used to identify and quantify streak characteristics. We used a method of vortex recognition to extract spanwise vortices in the x&ndash;z plane. Analysis of the interactions among coherent structures showed that the three standard vortex models all gave reasonably close results. The attached eddy vortex model provides a good explanation of the linear dimensions of streaky structures with respect to the water depth and Q2 and Q4 events, whereby it can be augmented to form the quasi-streamwise vortex model. The legs of a hairpin vortex envelop low-speed streaky structures and so move in the streamwise direction; lower-velocity vortex legs also gradually accumulate into a streamwise vortex. Statistical analysis allowed us to combine our present results with some previous research results to propose a mechanism for the formation of streaky structures. This study provides a deeper understanding of the interrelationships among different vortex models