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Large deep neural network (DNN) models pose the key challenge to energy efficiency due to the significantly higher energy consumption of off-chip DRAM accesses than arithmetic or SRAM operations. It motivates the intensive research on model compression with two main approaches. Weight pruning leverages the redundancy in the number of weights and can be performed in a non-structured, which has higher flexibility and pruning rate but incurs index accesses due to irregular weights, or structured manner, which preserves the full matrix structure with a lower pruning rate. Weight quantization leverages the redundancy in the number of bits in weights. Compared to pruning, quantization is much more hardware-friendly and has become a "must-do" step for FPGA and ASIC implementations. Thus, any evaluation of the effectiveness of pruning should be on top of quantization. The key open question is, with quantization, what kind of pruning (non-structured versus structured) is most beneficial? This question is fundamental because the answer will determine the design aspects that we should really focus on to avoid the diminishing return of certain optimizations. This article provides a definitive answer to the question for the first time. First, we build ADMM-NN-S by extending and enhancing ADMM-NN, a recently proposed joint weight pruning and quantization framework, with the algorithmic supports for structured pruning, dynamic ADMM regulation, and masked mapping and retraining. Second, we develop a methodology for fair and fundamental comparison of non-structured and structured pruning in terms of both storage and computation efficiency. Our results show that ADMM-NN-S consistently outperforms the prior art: 1) it achieves 348× , 36× , and 8× overall weight pruning on LeNet-5, AlexNet, and ResNet-50, respectively, with (almost) zero accuracy loss and 2) we demonstrate the first fully binarized (for all layers) DNNs can be lossless in accuracy in many cases. These results provide a strong baseline and credibility of our study. Based on the proposed comparison framework, with the same accuracy and quantization, the results show that non-structured pruning is not competitive in terms of both storage and computation efficiency. Thus, we conclude that structured pruning has a greater potential compared to non-structured pruning. We encourage the community to focus on studying the DNN inference acceleration with structured sparsity.

With the rapid development of the metro, a series of problems caused by stray current are becoming increasingly serious. Evaluation of stray current is the primary but difficult step for dealing with the problems. In fact, due to metros are usually constructed by cut-an-cover tunnel, shield tunnel and viaduct, metro structure is one of the most important factors of stray current. It is of significant to evaluate stray current in the long-line with the variable metro structures. Based on this, a uniform model is built in this paper. The return current system is equivalent to multiple differential units considering the variability of the metro structure, differential units at each location can be set according to the actual metro structure. Further, uniform equations for solving stray current are deuced based on the electrical relationships of differential units. For variable metro structures, uniform boundary conditions are discussed to solve the equations. The model is verified by comparing the test data and simulation data of Shenzhen Metro. Finally, stray current along the long-line is evaluated in this paper. It is shown that stray current is smaller along the long-line which is formed by the viaduct.

Background Chest pain is the most common symptom of aortic dissection (AD), but it is often confused with other prevalent cardiopulmonary diseases. We aimed to develop deep-learning models (DLMs) with ECG and CXR features to detect AD and evaluate their performance. Methods This study included 43,473 patients in the emergency department (ED) between July 2012 and December 2019 for retrospective DLM development. A development cohort including 49,071 ED records (120 AD-type A and 64 AD-type B) was used to train DLMs for ECG and CXR, and 9,904 independent ED records (40 AD-type A and 34 AD-type B) were used to validate DLM performance. Human–machine competitions of ECG and CXR were conducted. Patient characteristics and laboratory results were used to enhance the diagnostic accuracy. The DLM-enabled AD diagnostic process was prospectively evaluated in 25,885 ED visits. Results The AUCs of the ECG and CXR models were 0.918 and 0.857 for detecting AD in a human–machine competition, respectively, which were better than those of the participating physicians. In the validation cohort, the AUCs of the integrated model were 0.882, 0.960, and 0.813 in all AD, AD-type A, and AD-type B patients, respectively, with a sensitivity of 100.0% and a specificity of 81.7% for AD-type A. In patients with chest pain and D-dimer tests, the DLM could predict more precisely, achieving a positive predictive value of 62.5% in the prospective evaluation. Conclusions DLMs may serve as decision-supporting tools for AD identification and facilitate differential diagnosis in patients with acute chest pain.

Catenary is essential for electric locomotives to obtain electric energy, and it is crucial to the normal and stable operation of electric locomotives. However, the catenary is completely exposed outdoors without backup equipment. Therefore, compared with other power supply equipment in traction substation, catenary is more likely to be affected by external geographical and meteorological factors. In order to comprehensively assess the probability and consequence of catenary failures under the impact of external geographical and meteorological factors, a risk assessment method for electrified railway catenary is proposed in this article. First, the influence of external geographical and meteorological factors on catenary failures is analyzed based on the actual operation records. Then, considering the high efficiency and service characteristics of railway transportation, the risk consequence indicators are established, and the cumulative risk of catenary failure is quantitatively evaluated. Based on this, the risk classification method is proposed, and the risk level of catenary is visualized with geographic information system (GIS) technology. Finally, the risk contribution indicator is proposed to describe the influence of catenary component on the total risk of catenary failures. The catenary failure records of Beijing–Shanghai Railway within the administration of Shanghai Railway Bureau in 2017 are used for a study case. The results show that the proposed method can comprehensively quantify and visualize the risk of catenary failures. Also, the critical components of the catenary system can be identified, which can provide effective information for the maintenance decision-making process.

Background Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are important risk factors for cardiovascular (CV) diseases and treating these factors simultaneously is recommended by current guidelines but only short-term clinical results were available. The objective of this study was to examine the longer-term efficacy and safety of fixed-dose combination (FDC) versus free combination of amlodipine and atorvastatin in patients with concomitant hypertension and hypercholesterolemia. Methods Patients with hypertension and hypercholesterolemia were stratified into three groups (FDC of amlodipine 5 mg/atorvastatin 10 mg [Fixed 5/10], FDC of amlodipine 5 mg/atorvastatin 20 mg [Fixed 5/20], and free combination of amlodipine 5 mg/atorvastatin 10 mg [Free 5/10]). After inverse probability of treatment weighting, the composite CV outcome, liver function, BP, LDL-C and glycated hemoglobin (HbA1c) changes were compared. Results A total of 1,788 patients were eligible for analysis and the mean follow-up period was 1.7 year. There was no significant difference in the composite CV outcome among the three groups during the 30-month follow-up period (Fixed 5/10 6.1%, Fixed 5/20 6.3% and Free 5/10 6.0%). The LDL-C level was significantly reduced in the Fixed 5/20 group (-35.7 mg/dL) compared to the Fixed 5/10 (-23.6 mg/dL) and Free 5/10 (-10.3 mg/dL) groups (P=0.001 and

Objectives: This study aimed to compare the short-term and long-term follow-up outcomes of catheter-directed thrombolysis (CDT) with those of pulmonary artery embolectomy (PAE) for patients with acute pulmonary embolism (PE) included in a nationwide cohort. Background: Data allowing direct comparisons between CDT and PAE are lacking in the literature, and the optimal management of high-risk and intermediate-risk PE is still debated. Methods: A retrospective cohort study was conducted with data for 2001 through 2013 collected from the Taiwan National Health Insurance Research Database (NHIRD). Patients who were first admitted for PE and treated with either CDT or PAE were included and compared. In-hospital outcomes included in-hospital death and safety (bleeding and cardiac arrhythmias) outcomes. Follow-up outcomes included all-cause mortality and recurrent PE during the 1- and 2-year follow-up periods and through the last follow-up. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to minimize possible selection bias, including indices for multimorbidity such as the Charlson’s Comorbidity Index (CCI) and HAS-BLED scores. Results: A total of 389 patients treated between January 1, 2001, and December 31, 2013, were identified; 169 underwent CDT and 220 underwent PAE. After IPTW, there were no significant differences in in-hospital mortality (18.2% vs 21.3%; odds ratio 1.07, 95% confidence interval [CI]: 0.70–1.62) or the incidence of safety outcomes between the CDT and PAE groups. The risks of all-cause mortality (30% vs 29.5%; hazard ratio 1.16, 95% CI: 0.89–1.53), recurrent PE (7.2% vs 8.7%; subdistribution hazard ratio [SHR] 0.68, 95% CI: 0.39–1.21) and new-onset pulmonary hypertension (SHR 0.25, 95% CI: 0.05–1.32) were also not significantly different between the CDT and PAE groups at 2 years of follow-up. Subgroup analysis indicated that PAE may be associated with a more favorable 2-year mortality in patients Conclusions: In patients with PE who required reperfusion therapy, CDT and PAE resulted in similar in-hospital and long-term all-cause mortality rates and long-term rates of recurrent PE. Bleeding risks were also comparable in the 2 groups.

BACKGROUND: Delayed diagnosis or misdiagnosis of acute myocardial infarction (AMI) is not unusual in daily practice. Since a 12-lead electrocardiogram (ECG) is crucial for the detection of AMI, a systematic algorithm to strengthen ECG interpretation may have important implications for improving diagnosis. AIMS: We aimed to develop a deep learning model (DLM) as a diagnostic support tool based on a 12-lead electrocardiogram. METHODS: This retrospective cohort study included 1,051/697 ECGs from 737/287 coronary angiogram (CAG)-validated STEMI/NSTEMI patients and 140,336 ECGs from 76,775 non-AMI patients at the emergency department. The DLM was trained and validated in 80% and 20% of these ECGs. A human-machine competition was conducted. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the performance of the DLM. RESULTS: The AUC of the DLM for STEMI detection was 0.976 in the human-machine competition, which was significantly better than that of the best physicians. Furthermore, the DLM independently demonstrated sufficient diagnostic capacity for STEMI detection (AUC=0.997; sensitivity, 98.4%; specificity, 96.9%). Regarding NSTEMI detection, the AUC of the combined DLM and conventional cardiac troponin I (cTnI) increased to 0.978, which was better than that of either the DLM (0.877) or cTnI (0.950). CONCLUSIONS: The DLM may serve as a timely, objective and precise diagnostic decision support tool to assist emergency medical system-based networks and frontline physicians in detecting AMI and subsequently initiating reperfusion therapy.

Pparg, a nuclear receptor, is downregulated in basal subtype bladder cancers that tend to be muscle invasive and amplified in luminal subtype bladder cancers that tend to be non-muscle invasive. Bladder cancers derive from the urothelium, one of the most quiescent epithelia in the body, which is composed of basal, intermediate, and superficial cells. We find that expression of an activated form of Pparg (VP16;Pparg) in basal progenitors induces formation of superficial cells in situ, that exit the cell cycle, and do not form tumors. Expression in basal progenitors that have been activated by mild injury however, results in luminal tumor formation. We find that these tumors are immune deserted, which may be linked to down-regulation of Nf-kb, a Pparg target. Interestingly, some luminal tumors begin to shift to basal subtype tumors with time, down-regulating Pparg and other luminal markers. Our findings have important implications for treatment and diagnosis of bladder cancer., PPARg is differentially expressed in bladder cancer subtypes. Here, the authors show in mice that when an activated form of PPARg is expressed in basal bladder cells tumours do not form, however in the presence of injury the basal cells differentiate into luminal cells.

Background To evaluate the immune function of gastric cancer patients after single-incision laparoscopic distal gastrectomy (SIDG) or multiport laparoscopic distal gastrectomy (MLDG) guided by enhanced recovery after surgery (ERAS). Methods A retrospective cohort study was performed on 120 patients who underwent laparoscopic distal gastrectomy for gastric cancer. The patients were divided into two groups according to operation method: group A (MLDG) and group B (SIDG), both guided by ERAS concept. The indicators reflecting immune function and inflammation, such as CD3+, CD4+, CD8+ and NK cell count, CD4+/CD8+ cell ratios, IgA, IgM and IgG levels, C-reactive protein (CRP), total lymphocyte count (TLC) and neutrophil-to-lymphocyte ratio (NLR) were tested 3 days and 7 days after surgery. Results The skin incision length of patients in group B was significantly shorter than that in group A, but the operation time was significantly longer in group B than that in group A (P P P > 0.05). On the 7th day after surgery, the immune indexes of both groups recovered somewhat, approaching the preoperative level (P > 0.05). Inflammation indexes increased 3 days after surgery and decreased 7 days after surgery in both groups, among them the CRP level in group A was higher than that in group B (P Conclusion Compared with MLDG guided by ERAS, SIDG under the guidance of the ERAS concept has better cosmetic effect and similar effect on immune function of gastric cancer patients.

The conventional spherical conformal phased-array antenna (SPAA) has a wide beam coverage but suffers from a high profile due to its spherical conformal carrier. In this article, a low-profile conformal array antenna is modified from the conventional SPAA, which can be called the concave sector-cut spherical phased-array antenna (CSSPAA). A distributed aperture synthesis is employed to guarantee that the performance of the CSSPAA is close to that of the SPAA after reducing its height as much as possible. The CSSPAA’s height and the element’s half-power beamwidth (HPBW) are properly designed to minimize the blockage influence due to the special topology of the CSSPAA. A prototype CSSPAA with 48 elements is designed as an example, and the height of the CSSPAA is 43% lower than that of the SPAA with the similar performance in the hemispherical beam coverage. Both numerical and experimental results indicate the effectiveness of the developed method.

During the dynamic operation of the dc metro system, excessive neutral direct current (NDC) of the grounding transformer appears in the ac power system, which has not been clarified until now. Seriously, the high-level NDC has led the transformer under dc bias, which affects the lifespan and safety of transformers and systems. To analyze the NDC of the grounding transformer with the dynamic metro train, the synchronous monitor schemes of the traction current and rail potential of the dc metro system and the NDC of the nearby transformer are proposed. The relationship between the metro rail potential and NDC is analyzed and presented. Based on the monitor data analysis, the negative correlations are found in the directions and magnitudes of the RSP and the NDC. To explain the reasons for the relationship, the numerical simulation is proposed based on the structure of the monitored metro line and substation. Moreover, the universality of the relationship is verified through the coupled simulated model. Results show that the NDC is commonly flowing into the transformer as the rail potential is positive. Moreover, the NDC may exceed the allowable threshold of transformers in acceleration and brake conditions of the dynamic train.

Objective This study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). Methods Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding. Results Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban. Conclusion Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality., The outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) or atrial fibrillation (AF) are not known. A total of 3591 patients with active cancers were studied (907 on dabigatran; 2684 on rivaroxaban). In comparison with rivaroxaban, the use of dabigatran may be associated with lower risk of cancer‐related death and all‐cause mortality.

Background: Primary tracheal adenoid cystic carcinoma is a rare, slow-growing pulmonary malignancy. Due to the low incidence, clinicians are poor in the diagnosis and treatment of such disease, which is prone to cause misdiagnosis or missed diagnosis, consequently leading to delayed treatment. Case Presentation: Here, we reported a case of a 72-year-old woman who was diagnosed as primary bronchial adenoid cystic carcinoma after three years. At the time of final diagnosis, lesion involvement was seen in the entire bronchus and radical treatment was not available. Conclusions: Endoscopic bronchoscopy and palliative radiotherapy can relieve the symptoms of the patient and make the patient survive with the tumor for a long time.

In this study, we aim to discover the importance of long non-coding RNA cyclin-dependent kinase 6 (CDK6)-AS1 in lipopolysaccharide (LPS)-induced HK-2 cells. We treated the HK-2 cells with LPS and knocked down CDK6-AS1 in HK-2 cells and then analyzed the effects of CDK6-AS1 on the viability of cell, cell apoptosis, the expression of cytokines via MTT, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and qPCR. The results showed that silencing CDK6-AS1 alleviated LPS-induced inhibition of HK-2 cell proliferation, release of IL-1β, IL-8, IL-6, and TNF-α, cell apoptosis, and decrease in mitochondrial membrane potential. In addition, decreasing the level of CDK6-AS1 inhibited the reduction of Bcl-2 levels, the expression of Bax, cleaved caspade-9, and cleaved caspase-3, induced by LPS. In conclusion, lowering CDK6-AS1 level alleviates LPS-induced inflammatory damage in HK-2 cells.

All-solid-state Z-scheme photocatalysts for overall water splitting to evolve H2 is a promising strategy for efficient conversion of solar energy. However, most of these strategies require redox mediators. Herein, a direct Z-scheme photoelectrocatalytic electrode based on a WO3-x nanowire-bridged TiO2 nanorod array heterojunction is constructed for overall water splitting, producing H2. The as-prepared WO3-x/TiO2 nanorod array heterojunction shows photoelectrochemical (PEC) overall water splitting activity evolving both H2 and O2 under UV–vis light irradiation. An optimum PEC activity was achieved over a 1.67-WO3-x/TiO2 photoelectrode yielding maximum H2 and O2 evolution rates roughly 11 times higher than that of pure TiO2 nanorods without any sacrificial agent or redox mediator. The role of oxygen vacancy in WO3-x in affecting the H2 production rate was also comprehensively studied. The superior PEC activity of the WO3-x/TiO2 electrode for overall water splitting can be ascribed to an efficient Z-scheme charge transfer pathway between the WO3-x nanowires and TiO2 nanorods, the presence of oxygen vacancies in WO3-x, and a bias potential applied on the photoelectrode, resulting in effective spatial charge separation. This study provides a novel strategy for developing highly efficient PECs for overall water splitting.

Background Inflammatory processes have been implicated in the development of chronic kidney disease (CKD). We investigated the association of a large panel of inflammatory biomarkers reflecting aspects of immunity with kidney function and CKD incidence. Methods We used data from two independent population-based studies, KORA F4 (discovery, n = 1110, mean age 70.3 years, 48.7% male) and ESTHER (replication, n = 1672, mean age 61.9 years, 43.6% male). Serum levels of biomarkers were measured using proximity extension assay technology. The association of biomarkers with estimated glomerular filtration rate (eGFR) at baseline and with incident CKD was investigated using linear and logistic regression models adjusted for cardiorenal risk factors. Independent results from prospective analyses of both studies were pooled. The significance level was corrected for multiple testing by false-discovery rate (PFDR Results In the KORA F4 discovery study, 52 of 71 inflammatory biomarkers were inversely associated with eGFR based on serum creatinine. Top biomarkers included CD40, TNFRSF9 and IL10RB. Forty-two of these 52 biomarkers were replicated in the ESTHER study. Nine of the 42 biomarkers were associated with incident CKD independent of cardiorenal risk factors in the meta-analysis of the KORA (n = 142, mean follow-up 6.5 years) and ESTHER (n = 103, mean follow-up 8 years) studies. Pathway analysis revealed the involvement of inflammatory and immunomodulatory processes reflecting cross-communication of innate and adaptive immune cells. Conclusions Novel and known biomarkers of inflammation were reproducibly associated with kidney function. Future studies should investigate their clinical utility and underlying molecular mechanisms in independent cohorts.

This study primarily used metal-organic chemical vapor deposition to grow gallium nitride (GaN) light-emitting diode (LED) structures with InGaN quantum wells (QWs). During the InGaN QW growing process, an identical concentration of trimethylindium gas was prepared and introduced at different times (Before(B), Middle(M), and After(A)) into the QW structures for an investigation of the variation in GaN LED luminous efficacy. Because of segregation resulting from the different concentrations of In content of the InGaN QWs during the process and because of the stress resulting from lattice mismatch between atoms, the interaction between segregation and stress forms quantum dots (QDs). Under processes with the appropriate parameters, the QDs can improve the luminous efficacy of GaN LEDs. Postprocess LEDs were measured for their electroluminescence, photoluminescence, cathodoluminescence, thermal stability, light output power, and external quantum efficiency. The QW structures were analyzed and observed using high-resolution transmission electron microscopy. The results revealed that the Before (B) LED had the greatest light output power at 46.6 mW, an increase of approximately 15.6%. Thermal annealing was then used to treat the LED at 850 °C, after which the photoluminescence intensity increased by 1.7 times.

BACKGROUND: Shoulder pain is one of the most common musculoskeletal concerns in manual wheelchair users including among athletes. However, there is a paucity of research characterizing both shoulder pain and shoulder pathology in this population. OBJECTIVE: To characterize and compare the prevalence of current shoulder pain and ultrasound metrics of shoulder pathology between wheelchair athletes, nonathletic wheelchair users, and nonwheelchair users. DESIGN: Cross-sectional. SETTING: Chicago-area adaptive sport teams/programs and musculoskeletal clinics. PARTICIPANTS: Thirty-four wheelchair athletes, six nonathletic wheelchair users, and 12 nonwheelchair users. METHODS: Self-reported shoulder pain was assessed by questionnaire and Wheelchair User Shoulder Pain Index (WUSPI). Shoulder physiology and pathology were assessed by physical and ultrasound evaluation of both shoulders by a sports medicine physician. MAIN OUTCOME MEASURES: Questionnaire outcomes: Prevalence of current shoulder pain, total WUSPI score. Physical examination outcomes: total Physical Examination of Shoulder Scale (PESS) score. Sonographic outcomes: Acromiohumeral distance (AHD) and presence of shoulder pathology. RESULTS: The majority of wheelchair athletes (68%) and nonathletic wheelchair users (67%) experienced shoulder pain since using a manual wheelchair. Wheelchair basketball players had a mean WUPSI score of 17.2 (SD = 21.8), and athletes participating in handcycling, sled hockey, and quad rugby had mean scores of 4.91 (SD = 8.32), 7.76 (SD = 13.1), and 4.29 (SD = 7.75), respectively. Shoulder pathology was observed in 14 of 31 (45%) wheelchair athletes and 4 of 6 (67%) nonathletic wheelchair users (p = .41). CONCLUSIONS: Although wheelchair use is a risk factor for shoulder pain, participation in amateur wheelchair sports may not be associated with increased risk of shoulder pain. It is possible that overhead sports such as wheelchair basketball may define a unique high-risk group. Further study is needed to examine this relationship and to determine whether there are differences between specific wheelchair sports.

Summary Background A peroneal flap, the boneless version of fibula flap, is considered as the equivalent of radial forearm flap of the lower leg. Because it is thinner than an anterolateral thigh (ALT) flap, the use of a peroneal flap is a viable option for the repair of soft tissue defects when a thin flap could bring about better functional and cosmetic outcomes. In this article, we describe the details of peroneal flap harvest and present our experience with the use of peroneal flaps for head and neck reconstruction. Materials and Methods Between 1996 and 2017, a total of 265 peroneal flaps were used to reconstruct a variety of head and neck defects. With the same vascular anatomy and slight modifications to the harvesting technique of a fibula flap, a peroneal flap can be harvested within 1–2 h. All medical records were retrospectively reviewed. Results A peroneal flap can be harvested as different types of chimeric flaps to fit a variety of head and neck defects. The peroneal flap failure rate was 3.4% and the postoperative complication rate was 12.8%. Conclusion A peroneal flap might be an alternative option for the reconstruction of head and neck defects.

Aims/Introduction Emerging evidence suggests that expression quantitative trait loci (eQTLs) are more likely to associate with complex diseases. Transient receptor potential cation channel subfamily M member 5 (TRPM5) is a ubiquitously expressed voltage‐gated cation channel that acts indispensably to trigger insulin secretion in pancreatic β‐cells. The present study evaluated the association between TRPM5 eQTL single‐nucleotide polymorphisms and the risk of gestational diabetes mellitus (GDM) in a Chinese population. Materials and Methods A total of 380 unrelated Chinese pregnant women including 241 GDM patients and 139 controls were included in this study. The eQTL single‐nucleotide polymorphisms of TRPM5 were obtained from the GTEx eQTL Browser, and were subsequently genotyped using the Agena MassARRAY iPLEX platform. Results Logistic regression analysis and linear regression analysis showed that rs35197079 and rs74848824 were significantly associated with reduced GDM risk and lower fasting plasma glucose levels after adjusting confounder factors in dominant genetic models. Stratification analysis based on pre‐pregnancy body mass index validated a strong association between rs35197079 and GDM susceptibility in underweight and normal weight individuals. Luciferase and electrophoretic mobility shift assays carried out in rat pancreatic β‐cells showed that rs35197079 was functional. Conclusions The TRPM5 eQTL single‐nucleotide polymorphism rs35197079 was associated with decreased GDM susceptibility in a Chinese population, especially in underweight and normal weight pregnant women, and it was functional in modulating gene transcription., In the present study, for the first time, we systematically examined the relationship between transient receptor potential cation channel subfamily M member 5 expression quantitative trait loci single‐nucleotide polymorphisms and gestational diabetes mellitus susceptibility. We identified that rs35197079 was significantly associated with decreased gestational diabetes mellitus risk in a Chinese population, and it could function to modulate gene transcription.

We propose a power divider comprising of two parallel λ/4 coupled lines with a shared input signal line. An isolation resistor R is included to enhance the output-port reflection coefficients (S22 and S33) and the isolation between the output ports (S32 and S23). In theory, the power divider can achieve perfect input-port reflection coefficient (S11) and equal power coupling from the input to the outputs (i.e. S21 = S31). To achieve compact chip area, three prototyped power dividers with single-spiral- structure are designed and implemented. Tapered width from 8 to 3 μm is used at the output port transmission lines (TLs) (the first power divider) or the input port TL (the second and the third power dividers) to compensate for the single spiral structure for its non-ideality. This leads to enhancement of the reflection coefficients, and amplitude imbalance (AI) and phase difference (PD) of S21 and S31 of the power dividers. Prominent results are obtained. For instance, the second power divider (divider-2) occupies a chip area of 0.02 mm2 (i.e. 2.4 × 10–4λ02), one of the smallest normalized chip areas ever reported for millimeter-wave power dividers. At 33 GHz, divider-2 achieves decent S11 of −13.4 dB, S22 of −17.6 dB, S33 of −22.1 dB, S32 of −17.1 dB, S21 of − 4.68 dB, S31 of − 4.37 dB, AI of −0.31 dB, and PD of − 1.1°. The remarkable results of the power divider indicate that it is suitable for Ka-band communication systems.

The incidence of herpes zoster in psoriasis patients is higher than in the general population. However, the association between herpes zoster risk and different systemic therapies, especially biologic agents, remains controversial. This study investigated the association between herpes zoster risk and several systemic antipsoriasis therapies. This prospective open cohort study was conducted using retrospectively collected data from the Taiwan National Health Insurance Research Database. We included 92,374 patients with newly diagnosed psoriasis between January 1, 2001, and December 31, 2013. The exposure of interest was the “on-treatment” effect of systemic antipsoriasis therapies documented by each person-quarter. The outcome was the occurrence of newly diagnosed herpes zoster. During a mean follow-up of 6.8 years, 4834 (5.2%) patients were diagnosed with herpes zoster after the index date. Among the systemic antipsoriasis therapies, etanercept (hazard ratio [HR] 4.78, 95% confidence interval [CI] 1.51–15.17), adalimumab (HR 5.52, 95% CI 1.72–17.71), and methotrexate plus azathioprine (HR 4.17, 95% CI 1.78–9.82) were significantly associated with an increased risk of herpes zoster. By contrast, phototherapy (HR 0.76, 95% CI 0.60–0.96) and acitretin (HR 0.39, 95% CI 0.24–0.64) were associated with a reduced risk of herpes zoster. Overall, this study identified an association of both etanercept and adalimumab with an increased risk of herpes zoster among psoriasis patients. Acitretin and phototherapy were associated with a reduced risk.

In DC metro systems, the stray current may cause many challenges for the nearby metal structures and the AC power systems, such as the corrosion of the buried pipes and the grounding grids of substations. Therefore, calculating the stray current and analyzing the distribution characteristics of the stray current are necessary for the design of the buried pipelines and substations. To obtain the stray current, considering the through-type structure characteristics of the return current system and the traction power supply system, a multiple power supply sections simulation model (multiple-section model) of stray current is proposed. In the proposed model, the train is equivalent to two dc current sources, and the dynamic results can be completed. Through comparing the rail potentials of simulation results and the field test data of the Shenzhen metro line, the proposed model is verified. And based on the proposed model of the Shenzhen metro line, the stray current distributions are obtained and analyzed. The results indicate that the stray current distribution has a certain periodicity which is approximately equal to the headway time of the train.

A compact, accurate, and bitwidth-programmable in-memory computing (IMC) static random-access memory (SRAM) macro, named CAP-RAM, is presented for energy-efficient convolutional neural network (CNN) inference. It leverages a novel charge-domain multiply-and-accumulate (MAC) mechanism and circuitry to achieve superior linearity under process variations compared to conventional IMC designs. The adopted semi-parallel architecture efficiently stores filters from multiple CNN layers by sharing eight standard 6T SRAM cells with one charge-domain MAC circuit. Moreover, up to six levels of bit-width of weights with two encoding schemes and eight levels of input activations are supported. A 7-bit charge-injection SAR (ciSAR) analog-to-digital converter (ADC) getting rid of sample and hold (S&H) and input/reference buffers further improves the overall energy efficiency and throughput. A 65-nm prototype validates the excellent linearity and computing accuracy of CAP-RAM. A single 512x128 macro stores a complete pruned and quantized CNN model to achieve 98.8% inference accuracy on the MNIST data set and 89.0% on the CIFAR-10 data set, with a 573.4-giga operations per second (GOPS) peak throughput and a 49.4-tera operations per second (TOPS)/W energy efficiency., This work has been accepted by IEEE Journal of Solid-State Circuits (JSSC 2021)

We present the design and analysis of G-band CMOS Wilkinson power dividers and dual balun for G-band communication and imaging systems. Miniature spiral and U-shaped four-way Wilkinson power dividers, which are based on three two-way Wilkinson power dividers, are designed and implemented. Miniature spiral dual balun, which is equivalent to an upper balun and a lower balun in parallel, is also designed and implemented for comparison. These devices are planar and symmetrical, and their main structure is implemented by the 2.34-µm-thick topmost metal to minimize the resistive loss. This leads to low insertion loss, and small amplitude imbalance (AI) magnitude and phase difference (PD) deviation. For instance, the spiral four-way Wilkinson power divider occupies 0.033 mm2 chip area and achieves S11 of − 11.4 dB, S21 of − 6.271 dB, S31 of − 6.445 dB, S41 of − 6.676 dB, and S51 of − 6.111 dB at 180 GHz, one of the smallest chip areas and lowest insertion losses for four-way power dividers with similar operation frequency. The corresponding AI magnitude and PD deviation are 0.565 dB and 3.2°, respectively. Moreover, the spiral dual balun occupies 0.026 mm2 chip area and achieves S11 of − 10.6 dB, S21 of − 7.549 dB, S31 of − 7.1 dB, S41 of − 7.598 dB, and S51 of − 7.352 dB at 180 GHz. The corresponding AI magnitude and PD deviation are 0.498 dB and 5.7°, respectively. The prominent results of the spiral and U-shaped four-way Wilkinson power dividers, and the spiral dual balun indicate that they are suitable for power division/combination in G-band systems.

The Standards Coordinating Body for Gene, Cell, and Regenerative Medicines and Cell-Based Drug Discovery (SCB) supports the development and commercialization of regenerative medicine products by identifying and addressing industry-wide challenges through standards. Through extensive stakeholder engagement, the implementation of rapid microbial testing methods (RMTMs) was identified as a high-priority need that must be addressed to facilitate more timely release of products. Since 2017, SCB has coordinated efforts to develop standards for this area through surveys, weekly meetings, workshops, leadership in working groups and participation in standards development organizations. This article describes the results of these efforts and discusses the current landscape of RMTMs for regenerative medicine products. Based on discussions with stakeholders across the field, an overview of traditional culture-based methods and limitations, alternative microbial testing technologies and current challenges, fit-for-purpose rapid microbial testing and case studies, risk-based strategies for selection of novel rapid microbial test methods and ongoing standards efforts for rapid microbial testing are captured here. To this end, SCB is facilitating several initiatives to address challenges associated with rapid microbial testing for regenerative medicine products. Two documentary standards are under development: an International Organization for Standardization standard to provide the framework for a risk-based approach to selecting fit-for-purpose assays primarily intended for cell and gene therapy products and an ASTM standard guide focused on sampling methods for microbial testing methods in tissue-engineered medical products. Working with the National Institute of Standards and Technology, SCB expects to facilitate the process of developing publicly available microbial materials for inter-laboratory testing. These studies will help collect the data necessary to facilitate validation of novel rapid methods. Finally, SCB has been working to increase awareness of, dialog about and participation in efforts to develop standards in the regenerative medicine field.

Background Conventional percutaneous vertebroplasty (PVP) are mainly guided by C-arm fluoroscopy, and it usually leads to excessive X-ray radiation exposure to patients, surgeons, and anesthetists. Moreover, multi-time fluoroscope may prolong the operation time. 3D-printed template could help minimize fluoroscopy shot times and fluoroscopy dosage during operation, and shorten operation time. We perform this study to compare the efficacy and accuracy of PVP assisted by “three-dimensional printed individual guide template” versus conventional PVP. Method Patients who suffered acute painful single segment osteoporotic vertebral compression fracture(OVCF) needed operative treatment were randomly assigned into three-dimensional printing individual guide template-assisted percutaneous vertebroplasty group (group A) or conventional PVP guided by C-arm fluoroscopy group (group B) at a 1:1 ratio. Fluoroscopy times for puncture points (FTPP), total radiation dosages (TRD), total fluoroscopy time (TFT), and total operation time (TOT) were recorded as the main evaluation factors to evaluate the two operation procedures. Results A total of 36 acute painful single segment OVCF patients were successfully operated on, and each group has 18 patients. None of the patients presented symptomatic complications. The surgical success rate in group A was 94.4%(17/18), one patient in the group A was failed and then operated by conventional procedure. FTPP (1.8 ± 0.8 in group A vs 5.2 ± 1.9 in group B, P < 0.05), TRD (4.9 ± 0.9 mGy vs 7.9 ± 1.6 mGy, P < 0.05), TFT (16.7 ± 2.9 vs 26.6 ± 5.3, P < 0.05), and total operation time (19.4 ± 2.4 min vs 27.8 ± 4.0 min, P < 0.05) were presented statistically difference in the two groups. The incidence of cement leakage occurred in group A (3/18, 16.7%) was less than that occurred in group B (7/18, 38.9%) (P > 0.05). Conclusions Compared with the conventional PVP, “three-dimensional-printed individual guide template-assisted PVP” could minimize fluoroscopy shot times during operation and fluoroscopy dosage, shorten operation time, and is a more precise and feasible operation method. Trial registration The present study was registered with the Chinese Clinical Trial Registry (ChiCTR) (http://www.chictr.org.cn), and its registration no. is ChiCTR1900024283.

Always-on keyword spotting (KWS) that detects wake-up words has been the indispensable module in the voice interaction system. However, the ultra-low-power embedded devices put forward strict requirements on energy consumption, latency, and recognition accuracy of KWS. In this work, we propose a near-sensor processing architecture of feature-configurable distributed network (NS-FDN) for always-on KWS applications. The proposed distributed network adapts to the flexible keywords demands in the actual scene by splitting the conventional single network into distributed sub-networks. We design a channel-independent training framework to improve the recognition accuracy of distributed networks. The speech features are evaluated and the redundancy is reduced in NS-FDN, which can also configure the speech features to further reduce the computing complexity and improve processing speed. For deeper optimization, we implement a 65nm-process prototype chip with near-sensor mixed-signal processing architecture avoiding energy-consuming analog-to-digital converter. By improving the system, algorithm, and hardware designs of the KWS, our co-optimized architecture eliminates the energy consumption bottleneck long-standing in conventional KWS systems and achieves state-of-the-art system performance. The experiment results show that NS-FDN achieves 31.6% energy consumption savings, 1.6 times memory savings, 57 times speedup, and 3.4% higher recognition accuracy compared with the state of the art.

A three-stage four–way 90–101 GHz power amplifier (PA) on 90 nm CMOS is reported. The PA consists of a meandrous four-way Wilkinson power divider, and common-source (CS) input and gain stages with ...

This study proposes a cloud tele-measurement technique on an electromechanical system, and uses a neural network algorithm based on principal-component analysis (PCA) to quickly diagnose its performance. Three vibration, three temperature, electrical voltage, and current sensors were mounted on the electromechanical system, and the external braking device was used to provide different load-states to simulate the operating states of the motor under different conditions. Moreover, a single-chip multiprocessor was used through the sensor to instantly measure the various load-state simulations of the motor. The operating states of the electromechanical system were classified as normal, abnormal, and required-to-be-turned-off states using a principal-component Bayesian neural network algorithm (PBNNA), to enable their quick diagnosis. Furthermore, PBNNA successfully reduces the dimensionality of the multivariate dataset for rapid analysis of the electromechanical system’s performance. The accuracy rates of health-diagnosis based on the Bayesian neural network algorithm and PBNNA models were obtained as 97.7% and 98%, respectively. Finally, the single-chip multiprocessor based on PBNNA is used to automatically upload the measurement and analysis results of the electromechanical system to the cloud website server. The establishment of this model system can optimize prediction judgment and decision-making based on the damage situation to achieve the goals of intelligence and optimization of factory reconstruction.

Plasmon-mediated photocatalytic water splitting has attracted extensive attention due to its bright future in using visible light, but the enhancement mechanism is still unclear, and the efficiency...

To achieve complete poverty alleviation, the improvement of infrastructure and living conditions is fundamental. Promoting the flow of factors through infrastructure investment, thereby reducing the income gap among residents, has become an important focus of poverty alleviation. Because of the high amount of investment in transportation infrastructure, greater attention has been paid to the income distribution effect it brings, but few studies have analysed the effect of rural highways on the income gap of farmers. Based on the panel data pertaining to 30 provinces in China from 1993 to 2013, this paper uses a fixed-effect model to test the impact of rural highways supply on the income gap of farmers. The empirical results show that: (1) The effect of Chinese rural highways on the farmers’ income gap among provinces is “U-shaped”. (2) Chinese national and provincial trunk highways are helpful in narrowing the farmers’ income gap among provinces. (3) The level of education, household productive fixed assets investment, level of urbanization, and level of regional economic development have multiple effects on the farmers’ income gap among provinces. Then, based on the empirical analysis, the paper analyzes the mechanism of rural highways affecting the income gap of farmers from a theoretical perspective and focuses on the causes of the “U-shaped” relationship between rural highways supply and farmers’ income gap.

A design of electric split-ring metamaterial (eSRM) with tunable terahertz (THz) free spectra range (FSR) characteristic is presented. The proposed eSRM is composed of double semicircle-shaped ring resonators with two connected metallic bars. By changing the radius of the semicircle-shaped ring resonators, the tuning ranges of FSR are 0.187 THz and 0.024 THz in transverse electric (TE) and transverse magnetic (TM) modes, respectively, which indicates eSRM could operate stably in TE and TM modes. Furthermore, eSRM exhibits switching and polarization-dependent characteristics by exploiting comb driver to control the distances between ring resonators along ${x}$ -and ${y}$ -axis directions. The electromagnetic responses could be tuned and switched between dual- and quad-resonance in both TE and TM modes. eSRM shows polarization angle-sensitive characteristic and the corresponding FSR could be tuned from 919 GHz to 336 GHz by changing the polarization angle of incident THz wave. In view of the above optical characteristics of eSRM, it is used for the sensing application exposed on different surrounding refraction index. The sensitivity, quality factor (Q-factor), and figure of merit (FOM) are calculated. The sensitivity is 0.457 THz/RIU and the average Q-factor and FOM are 40.65 and 35.47, respectively. These results indicate the proposed eSRM could be used in widespread applications, such as dual-/quad-resonance switches, polarization switches, and high-efficient environmental sensors. [2021-0006]

Little is known about the association between deep vein thrombosis (DVT) and arterial complications in patients with type 2 diabetes (T2DM). The aim of this retrospective cohort study was to assess the influence of prior DVT on major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs) in T2DM. A total of 1,628,675 patients with T2DM with or without a history of DVT from 2001 to 2013 were identified in the National Health Insurance Research Database of Taiwan. Before matching, the patients in the DVT group (n = 2020) were older than the control group (66.3 vs. 58.3 years). Patients in the DVT group were more likely to be female than the control group (54.3% vs. 47.5%). Before matching, the DVT group had higher prevalence of most comorbidities, more prescription of antiplatelet, antihypertensive agents and insulins, but less prescription of metformin and sulfonylurea. During a mean follow-up of 5.2 years (standard deviation: 3.9 years), the matched DVT group (n = 2017) have a significantly increased risk of MALE (8.4% vs. 5.2%; subdistribution hazard ratio [SHR] 1.60, 95% CI 1.34–1.90), foot ulcer (5.2% vs. 2.6%, SHR 1.96, 95% CI 1.57–2.45), gangrene (3.4% vs. 2.3%, SHR 1.44, 95% CI 1.10–1.90) and amputation (2.5% vs. 1.7%; SHR 1.42, 95% CI 1.03–1.95) than the 10,085 matched controls without DVT. They also tended to have a greater risk of all-cause mortality (38.1% vs. 33.1%; hazard ratio [HR] 1.18, 95% CI 1.09–1.27) and systemic thromboembolism (4.2% vs. 2.6%; SHR 1.56, 95% CI 1.22–1.99), respectively. We showed the presence of DVT may be associated with an increased risk of MALEs, major amputation, and thromboembolism, contributing to a higher mortality rate in T2DM.

There is a vast need for the use of digital display instruments in the manufacturing industry due to the simple operation and high precision. In addition to the numerical data acquisition, it is usually necessary to input additional text for the condition assessment as well. However, since most of these measure instruments do not provide any interfaces for users to access the values and it often lacks proper devices to input the text during the working process, these two tasks are highly human intensive under current conditions. In order to facilitate the smooth running of the work for operators, we propose a lightweight application which can be installed on smartphones or wearable devices using multidigit recognition and speech recognition techniques without changing too much of their workflow. The experimental results demonstrate that our approach can achieve high accuracy. Thus, the proposed solution can effectively resolve data input issues in the manufacturing sites, thereby reducing human labor, increasing productivity, and automating part of the process. Taking operators’ existing workflow into consideration for design can provide an application with an easy learning curve. Moreover, with the rapid and economical approach, companies can financially benefit from the development of this low-cost application, especially for small- and medium-sized enterprises.

The study aims to evaluate the effectiveness of an inquiry-based virtual reality (VR) science lab used in junior high school science classes. The Scientific Investigation VR Lab (SIVRLAB) is designed for 9th-grade students to learn about electrochemical cells. It is situated in a guided problem-solving context, where learners need to review the concept of oxidation-reduction reactions and assemble a voltaic cell to save a robot. The SIVRLAB features several cognitive supports and guides for students to plan and record experiments and resolve the problem. It has both a head-mounted display (HMD) version and a desktop VR version. The study recruited 66 9th graders from three classes to evaluate the two versions of the SIVRLAB. The students were assigned to one of three conditions, namely, (1) using immersive HMD SIVRLAB individually, (2) using desktop SIVRLAB individually, and (3) observing one student use immersive HMD SIVRLAB. The students were briefly introduced to the concept of electrochemical cells in the first class and were instructed to use the SIVRLAB sessions in the next class. The results from knowledge pre- and post-tests, a user experience survey, and students’ reflections were collected and analyzed qualitatively. The findings revealed that students who used the desktop VR obtained the highest test scores among the three groups. However, in the follow-up physical laboratory test, the performance of the students in the original HMD VR experimental group was better than those in the desktop VR experimental group. The paper also discusses student feedback and teacher observations regarding the design and interaction with immersive VR. Lastly, the implications of the study and recommendations for future studies are presented.

This paper discusses a systematic vehicle design process in which light weight is taken as the vehicle design objective, and the designed frame is analyzed in detail. The load condition of a vehicle under different circumstances is calculated according to the distances from the front and rear wheels to the centroid position. The stress on the components in the condition is analyzed by finite element analysis, the steering geometry of the vehicle is analyzed, and the vehicle's turning angle and radius are designed. The displacement of the vehicle under a load is calculated by rigidity analysis to determine the stability of the vehicle in motion. The experimental modal analysis of the real frame and the finite element method are verified mutually for the electric vehicle body-in-white (BIW) manufacturing process to determine the consistency of model formation and the real frame. In terms of the circuit design, we used no-fuse switches and fuses to provide overcurrent protection for the main power supply, and the chip is combined with an optically coupled circuit and current sensor, which is driven by a restriction controller for protection. Moreover, a solid-state relay (SSR) is used for current protection and for controlling the forward/reverse rotation of the motor.

BACKGROUND pT2+ prostate cancer (PCa), a term first used in 2004, refers to organ-confined PCa characterized by a positive surgical margin (PSM) without extracapsular extension. Patients with a PSM are vulnerable to biochemical recurrence (BCR) following radical prostatectomy (RP); however, whether adjuvant radiotherapy (aRT) is imperative to PSM after RP remains controversial. This study had the longest follow-up on pT2+ PCa after robotic-assisted RP since 2004. Moreover, we discussed our viewpoints on pT2+ PCa based on real-world experiences. AIM To conclude a 10-year surveillance on pT2+ PCa and compare our results with those of the published literature. METHODS Forty-eight patients who underwent robotic-assisted RP between 2008 and 2011 were enrolled. Two serial tests of prostate specific antigen (PSA) ≥ 0.2 ng/mL were defined as BCR. Various designed factors were analyzed using statistical tools for BCR risk. SAS 9.4 was applied and significance was defined as P < 0.05. Univariate, multivariate, linear regression, and receiver operating characteristic (ROC) curve analyses were performed for statistical analyses. RESULTS With a median follow-up period of 9 years, 25 (52%) patients had BCR (BCR group), and the remaining 23 (48%) patients did not (non-BCR group). The median time for BCR test was 4 years from the first postoperative PSA nadir. Preoperative PSA was significantly different between the BCR and non-BCR groups (P < 0.001), and ROC curve analysis of preoperative PSA suggested a cut-off value of 19.09 ng/mL (sensitivity, 0.600; specificity: 0.739). The linear regression analysis showed no correlation between time to BCR and preoperative PSA (Pearson’s correlation, 0.13; adjusted R2 = 0.026). CONCLUSION Robotic-assisted RP in pT2+ PCa of worse conditions can provide better BCR-free survival. A surgical technique limiting the PSM in favorable situations is warranted to lower the pT2+ PCa BCR rate. Preoperative PSA cut-off value of 19.09 ng/mL is a predictive factor for BCR. Based on our experiences and review of the literature, we do not recommend routine aRT for pT2+ PCa.

Objective: There is a high prevalence of obstructive sleep apnea (OSA) in pediatric and adult Down Syndrome (DS) patients that is refractory to adenotonsillectomy and continuous positive airway pressure. Newer treatment modalities have emerged with improved outcomes. The objective is to provide an updated systematic review and meta-analysis to analyze the clinical outcomes of OSA in pediatric and adult DS patients with hypoglossal nerve stimulation using Inspire, midline posterior glossectomy plus lingual tonsillectomy (MPG + LT), and combined genioglossus advancement plus radiofrequency (GGS + RF). Methods: A comprehensive literature search of PubMed and Google Scholar was performed followed by a meta-analysis. Studies with preoperative and post-operative Apnea Hypopnea Index (AHI) values were included with patients serving as their own control. Results: Across 5 studies, 56 patients were analyzed. The mean reduction in AHI was statistically significant before vs. after procedure ( P

With the rapid development of the DC metro system, the stray current may bring new challenges to the AC power system. Especially, the stray current of the DC metro system flowing in the AC power system may cause many serious consequences such as the corrosion of the grounding grids, plenty of harmonics, and the dc bias of transformers. Therefore, it is significant to evaluate the dc current distribution in the AC power system caused by the stray current. In order to evaluate the dc current distribution, a coupled simulation model both considering the DC metro system and the AC power system is proposed in this paper. Moreover, the earth and the grounding system are both used as the coupling elements in the proposed model. The correctness of the proposed model is verified by the comparison of the calculation results and the field test data. Furthermore, based the proposed model, the dc current distribution in the AC power system is evaluated and analyzed. The results indicate that the dc current distribution is affected by the trains operating conditions and the relative position between the DC metro system and the AC power system.

Biopharmaceutical manufacturing is an evolving industry with great potential to improve public health, but laden with technical and operational challenges. It has many features that are similar to other smart manufacturing industries, but it also has some unique features that are specific to the biological domain in which it operates. Both types of features have been carefully explored in recent industrial roadmaps to guide the research, development, and manufacturing of biopharmaceuticals. These roadmaps explicitly identify “fully automated facilities” and “knowledge management” as two of the critical enabling capabilities that will drive the biopharmaceutical industry in the next decade. This article describes these roadmaps to identify the emerging opportunities and future directions in this knowledge-intensive manufacturing industry. It also serves as a “call for action” for collaboration among key stakeholders, including the robotics and automation community. Note to Practitioners —The market for biopharmaceuticals has been rising rapidly in recent years. It is now a multibillion dollar industry with its own ecosystem of suppliers, medical professionals, drug delivery systems, and regulators. The healthcare benefits promised by biopharmaceuticals are impressive, but there are several research, development, and manufacturing challenges that must be overcome to deliver on these promises. The biopharmaceutical industry, in collaboration with academics and government laboratories, has published a series of roadmaps recently to address these challenges. “Fully automated facilities” and “knowledge management” have been explicitly identified in the roadmaps as two of the critical enablers to meet these challenges. This article summarizes the findings of these industrial roadmaps and provides a clear picture of the collaborative efforts needed to succeed in, and grow, this promising industry.

Background/Purpose: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. Methods: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). Results: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts

A confocal synchrotron radiation micro-X-ray fluorescence (μ-SRXRF) imaging setup based on Kirkpatrick–Baez (K–B) mirrors and polycapillary optics is described and characterized at the hard X-ray micro-focusing beamline (BL15U1) of the Shanghai Synchrotron Radiation Facility (SSRF). It provides a depth resolution of 10.2–26.5 μm in the energy range of 5.0–13.0 keV. A quantitative calculation method based on the fundamental parameter (FP) method was presented for elemental distribution images obtained with the confocal μ-SRXRF imaging setup. For each pixel of a depth-scanning measurement, quantitative calculation was performed considering the actual geometry of the setup and various emission paths of X-ray fluorescence (XRF). The initial inhomogeneous XRF intensity distribution maps from a National Institute of Standards and Technology (NIST) standard reference material (SRM) 611 form rather homogeneous concentration distribution maps after quantitative calculation. The combination of a confocal μ-SRXRF imaging technique with a quantitative calculation method is illustrated with the results of the analysis of an individual fluid inclusion within a natural beryl crystal. Non-destructive 3D XRF analysis by the confocal μ-SRXRF imaging technique will be effective for depth-structural and multi-elemental studies of many materials and allows studying more complicated phenomena.

Photocatalytic water splitting is an ideal way of generating hydrogen, a renewable energy source, from solar energy that would help solve environmental problems. However, current photocatalysts are...

The access of distributed generations (DGs) in the traction power supply system (TPSS) can not only make use of the renewable energy near the railway route, but also improve the condition of weak external power supply. In order to quantify the effect when DGs access TPSS, this study proposes a method for evaluating the power supply capability and quality of TPSS which considers the access of DGs. First, the method fully considers the randomness and uncertainty of the power provided by DGs and that consumed by electrical locomotives. A comprehensive model of TPSS with the access of DGs is built by means of the stochastic model, and then the index system for evaluating the power supply capability and quality of TPSS is formulated. Finally, the Monte Carlo simulation is applied to calculate the probabilistic load flow to obtain the evaluation indices. The proposed method is verified by simulating a typical TPSS in a remote mountain area. The results show that the method can quantify the power supply capability and quality of the system after the access of DGs. It can provide an intuitive conception of the power supply condition for design and operation personnel.

Background/Objective Breast biopsy and analysis of sentinel lymph nodes (SLNs) accurately predict tumor status in the affected basin and help in avoiding unnecessary axillary lymph node dissection, which is associated with remarkable morbidity risk. Blue dye and radioisotope are the most widely used mapping agents, but non-radioactive tracers of comparable accuracy warrant further investigation. This study aimed to investigate utilization of indocyanine green (ICG) fluorescence in sentinel node localization compared with blue dye and to assess the incremental value of ICG. Methods A total of 39 consecutive patients underwent sentinel lymph node biopsy (SLNB) (40 cases: 38 unilateral and 1 bilateral) with combined blue dye and ICG for localization. The obtained fluorescence images of the lymphatic system were investigated. Results All 84 lymph nodes removed in 40 procedures were identified by ICG, but only 37 were identified by blue dye. The ICG method identified an average of 2.1 SLNs in 39 of 40 cases with a detection rate of 97.5%, but only 0.93 SLN per case with blue dye. Subcutaneous lymphatic channel patterns were also detected by fluorescent imaging in 37 procedures, which all revealed lymphatic drainage toward the axilla except in one case with internal mammary pathway. Conclusion This study demonstrated the accuracy and safety of ICG for SLNB and its superiority to blue dye method in SLN localization. Therefore, ICG fluorescence method is safe and effective addition in breast clinical settings, wherein blue dye alone is used.

Arenaviruses are a large family of enveloped negative-strand RNA viruses that include several causative agents of severe hemorrhagic fevers. Currently, there are no FDA-licensed drugs to treat arenavirus infection except for the off-labeled use of ribavirin. Here, we performed antiviral drug screening against the Old World arenavirus lymphocytic choriomeningitis virus (LCMV) using an FDA-approved drug library. Five drug candidates were identified, including mycophenolic acid, benidipine hydrochloride, clofazimine, dabrafenib, and apatinib, for having strong anti-LCMV effects. Further analysis indicated that benidipine hydrochloride inhibited LCMV membrane fusion, and an adaptive mutation on the LCMV glycoprotein D414 site was found to antagonize the anti-LCMV activity of benidipine hydrochloride. Mycophenolic acid inhibited LCMV replication by depleting GTP production. We also found mycophenolic acid, clofazimine, dabrafenib, and apatinib can inhibit the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Owing to their FDA-approved status, these drug candidates can potentially be used rapidly in the clinical treatment of arenavirus and SARS-CoV-2 infection.