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Hip fractures are associated with a high risk of death; among those who survive a hip fracture, many experience substantial decreases in quality of life. A comprehensive understanding of the epidemiology and burden of hip fractures by country, age, gender, and sociodemographic factors would provide valuable information for healthcare policymaking and clinical practice. The Global Burden of Disease (GBD) study 2019 was a global-level study estimating the burden of 369 diseases and injuries in 204 countries and territories. An exploration and additional analysis of the GBD 2019 would provide a clearer picture of the incidence and burden of hip fractures.Using data from the GBD 2019, we asked, (1) What are the global, regional, and national incidences of hip fractures, and how did they change over a recent 30-year span? (2) What is the global, regional, and national burden of hip fractures in terms of years lived with disability, and how did it change over that same period? (3) What is the leading cause of hip fractures? (4) How did the incidence and years lived with disability of patients with hip fractures change with age, gender, and sociodemographic factors?This was a cross-sectional study. Participant data were obtained from the GBD 2019 (http://ghdx.healthdata.org/gbd-results-tool). The GBD study is managed by the WHO, coordinated by the Institute of Health Metrics and Evaluation, and funded by the Bill and Melinda Gates Foundation. It estimates the burden of disease and injury for 204 countries by age, gender, and sociodemographic factors, and can serve as a valuable reference for health policymaking. All estimates and their 95% uncertainty interval (UI) were produced using DisMod-MR 2.1, a Bayesian meta-regression tool in the GBD 2019. In this study, we directly pulled the age-standardized incidence rate and years lived with disability rate of hip fractures by location, age, gender, and cause from the GBD 2019. Based on these data, we analyzed the association between the incidence rate and latitude of each country. Then, we calculated the estimated annual percentage change to represent trends from 1990 to 2019. We also used the Spearman rank-order correlation analysis to determine the correlation between the incidence or burden of hip fractures and the sociodemographic index, a composite index of the income per capita, average years of educational attainment, and fertility rates in a country.Globally, hip fracture incidences were estimated to be 14.2 million (95% UI 11.1 to 18.1), and the associated years lived with disability were 2.9 million (95% UI 2.0 to 4.0) in 2019, with an incidence of 182 (95% UI 142 to 231) and 37 (95% UI 25 to 50) per 100,000, respectively. A strong, positive correlation was observed between the incidence rate and the latitude of each country (rho = 0.65; p0.001). From 1990 to 2019, the global incidence rate for both genders remained unchanged (estimated annual percentage change 0.01 [95% confidence interval -0.08 to 0.11]), but was slightly increased in men (estimated annual percentage change -0.11 [95% CI 0.01 to 0.2]). The years lived with disability rate decreased slightly (estimated annual percentage change 0.66 [95% CI -0.73 to -0.6]). These rates were standardized by age. Falls were the leading cause of hip fractures, accounting for 66% of all patients and 55% of the total years lived with disability. The incidence of hip fractures was tightly and positively correlated with the sociodemographic index (rho 0.624; p0.001), while the years lived with disability rate was slightly negatively correlated (rho -0.247; p0.001). Most hip fractures occurred in people older than 70 years, and women had higher incidence rate (189.7 [95% UI 144.2 to 247.2] versus 166.2 [95% UI 133.2 to 205.8] per 100,000) and years lived with disability (38.4 [95% UI 26.9 to 51.6] versus 33.7 [95% UI 23.1 to 45.5] per 100,000) than men.Hip fractures are common, devastating to patients, and economically burdensome to healthcare systems globally, with falls being the leading cause. The age-standardized incidence rate has slightly increased in men. Many low-latitude countries have lower incidences, possibly because of prolonged sunlight exposure. Policies should be directed to promoting public health education about maintaining bone-protective lifestyles, enhancing the knowledge of osteoporosis management in young resident physicians and those in practice, increasing the awareness of osteoporosis screening and treatment in men, and developing more effective antiosteoporosis drugs for clinical use.Level III, prognostic study.

Figure S6: IL-18 promotes proliferation and invasion of PC cells via the NF-κB pathway.

Purpose: We sought to find new immune-based treatments for pancreatic cancer.Experimental Design: We detected IL18 expression in plasma and specimens from patients with pancreatic cancer. We then investigated whether IL18 had a therapeutic effect for pancreatic cancer in vitro and in vivo and any underlying mechanisms.Results: Higher plasma IL18 was associated with longer overall survival (OS), but higher IL18 in pancreatic cancer tissues was associated with shorter OS and increased invasion and metastasis. Recombinant IL18 alone had no antitumor effect in the syngeneic mice with orthotopically transplanted tumors and promoted tumors in immunocompromised mice; it also facilitated immune responses in vitro and in vivo by augmenting the activity of cytotoxic T cells and NK cells in peripheral blood and lymph nodes. However, IL18 promoted the proliferation and invasion of pancreatic cancer cells, in vitro and in vivo, through the NF-κB pathway. Nevertheless, by coadministrating IL18 with BAY11-7082, an NF-κB inhibitor, we were able to prevent the procancerous effects of IL18 and prolong the survival time of the mice.Conclusions: IL18 has both cancer-promoting and cancer-suppressing functions. Although its single-agent treatment has no therapeutic effect on pancreatic cancer, when combined with the NF-κB pathway inhibitor, IL18 improved survival in a murine pancreatic cancer model. Our study implies the possibility of a combinational immunotherapy that uses IL18 and targets NF-κB pathway. Clin Cancer Res; 22(23); 5939–50. ©2016 AACR.

Supplemental Material and Methods

This article presents a 2.4-GHz 65-nm CMOS fully integrated nonlinear mixer-first receiver (RX) for the Internet of Things (IoT). To power efficiently improve the in-band interference resilience, we propose an inverter-based envelope-biased low noise amplifier (IBEB-LNA), which exploits dynamic biasing voltage generated from its input signal envelope to suppress the interferer in the amplitude domain. The achievable carrier-to-interference ratio (CIR) at ±3 and ±5 MHz is −45/−59 and −66/−65 dB, respectively. The proposed RX is suitable for ON–OFF keying (OOK) modulation with a 307-kb/s data rate, and the corresponding sensitivity is −83 dBm for keeping 0.1% bit error ratio (BER). The total power consumption is 2.05 mW.

This paper presents an 8-channel energy-efficient analog front-end (AFE) for neural recording, with improvements in power supply rejection ratio (PSRR) and dynamic range. The input stage in the low noise amplifier (LNA) adopts low voltage supply (0.35 V) and current-reusing to achieve ultralow power. To maintain a high PSRR performance while using such a low-voltage supply, a replica-biasing scheme is proposed to generate a stable bias current for the input stage of the LNA despite large supply interference. By exploiting the signal characteristics in the tetrode recording, an averaged local field potential (A-LFP) servo loop is introduced to extend the dynamic range without consuming too much extra power and chip area. The A-LFP signal is generated by integrating the four-channel PGA outputs from the same tetrode. Furthermore, the outputs of the programmable gain amplifier (PGA) are level shifted to bias the input nodes of the amplifier through large pseudo resistors, thus increase the maximum output range without distortion under the low-voltage supply. The proof-of-concept prototype is fabricated in a 65 nm CMOS process. Each recording channel including an LNA and a PGA occupies 0.04 mm $^2$ and consumes 340 nW from the 0.35 V and 0.7 V supply. Each A-LFP servo loop, which is shared by four recording channels, occupies 0.04 mm $^2$ and consumes 190 nW. The maximum gain of the AFE is 54 dB, and the input-referred noise is 6.7 $\mu$ V over the passband from 0.5 Hz to 6.5 kHz. Measurement also shows that the 0.35 V replica-biasing input stage can tolerate a large interferer up to 200 mVpp with a PSRR of 74 dB, which has been improved to 110 dB with a silicon respin that shields critical wires in the layout.

This brief presents a 64-channel fully-integrated wireless neural interfacing SoC implemented in a 65 nm CMOS process. To minimize the weight and size of the head-stage connected to the small experimental animals, the system is designed to be powered by either a single-coil 13.56 MHz wireless power receiver or a small-sized button cell battery. A replica-biased 0.35 V 110 dB PSRR LNA is introduced to tolerate the power supply noise inherently in wireless power harvesting and save power consumption. The recorded neural data is transmitted wirelessly by a 2.4/3.2 GHz dual-band OOK transmitter, which supports 54 Mb/s symbol rate, 44 pJ/bit meter-range wireless data transmission. To reduce the transmission BER, forward error correction with convolutional code and cyclic redundancy code is adopted.

This article presents a 13.56-MHz wireless power and data transfer receiver for implantable biomedical devices. To avoid the efficiency reduction of energy harvesting caused by the large amplitude modulation (AM) modulation depth (MD), and maintain low-power consumption for data receiving, an envelope-detector-based receiver with shifted limiters is designed for signal demodulation. The detectable MD is as low as 0.1%. Moreover, a dynamic impedance matching controller is proposed to adjust the input impedance of the rectifier automatically and thus optimize the power conversion efficiency (PCE). By using these techniques, when keeping the bit error rate (BER) of the proposed receiver to 10−3 for 100-kb/s data rate in the wireless amplitude shift keying (ASK) data receiver, the effective PCE of the corresponding wireless power receiver can be up to 75.4%.

Background The generation of subclonal (low-frequency) mutations is driven by tumor mutations and the relationship between the heterogeneity of tumor mutation abundance and non-small cell lung cancer (NSCLC) remains unknown. We investigate the role of allele frequency heterogeneity (AFH) defined by circulating tumor DNA (ctDNA) profiling in predicting prognosis in advanced NSCLC patients. Methods Publicly available data set of POPLAR (N=211) and OAK (N=642) trials were used for analyzing. A low ratio of allele frequency (AF) of a mutation to the maximum-somatic-allele-frequency (MSAF) was used to define the presence of AFH. The prognostic value of AF/MSAF ratio that was below a defined cutoff point in overall survival (OS) was evaluated using Cox-proportional hazards regression; and the structural break point was determined by LOESS regression and Chow test. The derived AFH was also explored in an independent cohort (N=259) of advanced NSCLC receiving first-line EGFR-TKIs from the First Affiliated Hospital of Guangzhou Medical University. Results In the POPLAR and OAK cohort, low AF/MSAF ratio was found to be significantly associated with unfavorable OS in univariate and multivariate analysis. The structural break point analysis demonstrated that AF/MSAF

Recent advances in the pathophysiologic understanding of coronavirus disease 2019 (COVID-19) suggests that cytokine release syndrome (CRS) has an association with the severity of disease, which is characterized by increased tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-2, IL-7, and IL-10. Hence, managing CRS has been recommended for rescuing severe COVID-19 patients. TNF-α, one of the pro-inflammatory cytokines commonly upregulated in acute lung injury, triggers CRS and facilitates SARS-CoV-2 interaction with angiotensin-converting enzyme 2 (ACE2). TNF-α inhibitors, therefore, may serve as an effective therapeutic strategy for attenuating disease progression in severe SARS-CoV-2 infection. Below, we review the possibilities and challenges of targeting the TNF-α pathway in COVID-19 treatment.

Neon (Ne) seeding is used to cool the edge plasma by radiation to protect the divertor tungsten (W) target in the Experimental Advanced Superconducting Tokamak (EAST). The W sputtering in the outer divertor target with Ne seeding is assessed by the divertor visible spectroscopy system. It is observed that the W sputtering flux initially increases with Ne concentration in the divertor despite the decreasing plasma temperature. After reaching a maximum around 25 eV, the W sputtering rate starts to decrease, presenting a suppression effect. The effect on the divertor W sputtering flux and yield due to the competition between the increase of the Ne concentration and the decrease of the plasma temperature is discussed. The results show that enough Ne seeding is essential to effectively reduce the electron temperature and thus to suppress W sputtering. Moreover, ELM suppression is observed when Ne and W impurities enter the core plasma, which could be correlated to the enhanced turbulence transport in the pedestal.

Recent advances [1] –[5] in capacitively-coupled chopper instrumentation amplifier (CCIA) demonstrated that long-term stabilized physiological signal recording strongly relies on the capability of the electrode-DC offset (EDO) cancellation. On the other hand, a short recovery time can alleviate the loss duration of the signal to be recorded when a sudden EDO change saturates the CCIA. This is crucial because the subject’s motion or the electrode’s reconnection to the subject can give rise to such sudden EDO change. Very often, employing a DC servo loop (DSL) can introduce a high-pass (HP) pole to the transfer function of the CCIA, suppressing the EDO nearby the DC frequency.

This work proposes a high-speed pipelined-two-step time-to-digital converter (TDC) with a dynamic time amplification (DTA) to improve the resolution at low power. The key element of this TDC is the DTA. It samples the residual time errors as voltages held in the MOM capacitors and discharges them to generate the amplified time difference. Thanks to the dynamic time-voltage-time conversion, the DTA realizes high linearity and power efficiency, and can be employed to build a pipeline TDC architecture with high sampling frequency because of its sample and hold operation. Moreover, the DTA maintains constant gain, so only a one-time forground calibration for gain mismatch is required in this TDC. Simulations show that the TDC designed in 65 nm CMOS achieves 8-bit, 1.75 ps of time resolution, and 1 LSB INL and 1.6 LSB DNL with one-time foreground calibration at 400 MHz sampling frequency while just consuming 726 μW power, which corresponds to 18.45 fJ/Conv. FoM.

Highlights • Initial blood urea nitrogen (BUN) and D-dimer levels were associated with mortality in COVID-19 patients. • Combination of BUN ≥ 4.6 mmol/L and D-dimer ≥ 0.845 μg/mL can identify patients at high risk of in-hospital mortality. • Development of a nomogram model based on initial BUN and D-dimer levels. • The nomogram could be a suitable and useful individualised tool to predict mortality in COVID-19 patients., The crude mortality rate in critical pneumonia cases with coronavirus disease 2019 (COVID-19) reaches 49%. This study aimed to test whether levels of blood urea nitrogen (BUN) in combination with D-dimer were predictors of in-hospital mortality in COVID-19 patients. The clinical characteristics of 305 COVID-19 patients were analysed and were compared between the survivor and non-survivor groups. Of the 305 patients, 85 (27.9%) died and 220 (72.1%) were discharged from hospital. Compared with discharged cases, non-survivor cases were older and their BUN and D-dimer levels were significantly higher (P < 0.0001). Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses identified BUN and D-dimer levels as independent risk factors for poor prognosis. Kaplan–Meier analysis showed that elevated levels of BUN and D-dimer were associated with increased mortality (log-rank, P < 0.0001). The area under the curve for BUN combined with D-dimer was 0.94 (95% CI 0.90–0.97), with a sensitivity of 85% and specificity of 91%. Based on BUN and D-dimer levels on admission, a nomogram model was developed that showed good discrimination, with a concordance index of 0.94. Together, initial BUN and D-dimer levels were associated with mortality in COVID-19 patients. The combination of BUN ≥ 4.6 mmol/L and D-dimer ≥ 0.845 μg/mL appears to identify patients at high risk of in-hospital mortality, therefore it may prove to be a powerful risk assessment tool for severe COVID-19 patients.

This paper presents a 2.0-2.9 GHz digital ring-based injection-locked clock multiplier (ILCM) in a 65 nm CMOS process. A self-alignment frequency tracking loop (SA-FTL) with background delay calibration is proposed to improve the accuracy of injection timing. Since the frequency mismatch of the free-running oscillator and the target frequency is minimized without delay error, the reference spur is reduced to -55.6 dBc, exhibiting 15.9 dB improvement comparing to the case that the SA-FTL is off. The proposed ILCM achieves 545 fs RMS jitter at 2.5 GHz output frequency with a power consumption of 3.1 mW, achieving the FoM of 240.3 dB.

COVID-19, the disease caused by SARS-CoV-2, is a highly contagious disease. The World Health Organization has declared the ongoing outbreak to be a global public health emergency. Currently, the research on SARS-CoV-2 is in its primary stages. Based on current published evidence, this review systematically summarizes the epidemiology, clinical characteristics, diagnosis, treatment and prevention of COVID-19. It is hoped that this review will help the public to recognize and deal with SARS-CoV-2, and provide a reference for future studies.

Supplemental Material, sj-pptx-1-cat-10.1177_1076029620982669 for Deep Venous Thrombosis in COVID-19 Patients: A Cohort Analysis by Chuanqi Cai, Yi Guo, Yun You, Ke Hu, Fei Cai, Mingxing Xie, Lu Yang, Ken Ling, Dawei Ye, Sanjay Misra, Weici Wang and Yiqing Li in Clinical and Applied Thrombosis/Hemostasis

To investigate the optimal scenario of impurity seeding to obtain divertor plasma detachment for target protection, experiments with Ar&D2 seeding from two different poloidal locations, the upper outer (UO) divertor target and lower outer (LO) target, were carried out on EAST. Partial energy detachment (the electron temperature near the strike point T e,spt ⩽ 10 eV) were obtained with Ar&D2 mixture puffing from the UO target and, for the first time, from the LO target into H-mode plasmas in the upper single null (USN) configuration. The peak heat flux q t on the UO target was significantly reduced (by ∼80%). The rollover of ion flux density j s did not appear probably due to insufficient momentum loss, which is independent of the puff locations. The poloidal asymmetries of particle and heat fluxes on the targets have also been investigated. The UO-dominant asymmetry of particle flux was reversed, while the UO-dominant asymmetry of heat flux was mitigated but not reversed. The plasma confinement dropped by only 14% and 8.2% in the LO-puff case and UO-puff case, respectively, during detachment. The high level of C may contributed greatly to the higher radiation in the bulk plasma region and the greater decline in W MHD in the LO-puff case.