A VHDL-AMS Based Time Domain Skin Depth Model for Edge Coupled Lossy Transmission Stripline

This contribution presents a time-domain model of the skin depth effect in a lossy transmission line. The model was developed and implemented in VHDL-AMS for a two wire edge coupled line but it is general and can be used for other types of lossy transmission line and high-frequency applications with skin depth effect. The salient feature of the model is the use of signal variation rate instead of frequency in the signal dependent resistance that models the skin depth losses. VHDL-AMS simulation experiments are presented to validate the model

AWG-DBR-based WDM transmitter fabricated in an InP generic foundry platform

We report a novel narrow-linewidth WDM transmitter operating at 10 Gbps per transmission channel with 275 kHz optical linewidth. The device, which integrates an AWG-based laser using selective DBR-mirrors with a Mach-Zehnder modulator array, has been fabricated in a multi-project wafer run in a generic InP-based foundry process.</p

Susceptible Workload Evaluation and Protection using Selective Fault Tolerance

Low power fault tolerance design techniques trade reliability to reduce the area cost and the power overhead of integrated circuits by protecting only a subset of their workload or their most vulnerable parts. However, in the presence of faults not all workloads are equally susceptible to errors. In this paper, we present a low power fault tolerance design technique that selects and protects the most susceptible workload. We propose to rank the workload susceptibility as the likelihood of any error to bypass the logic masking of the circuit and propagate to its outputs. The susceptible workload is protected by a partial Triple Modular Redundancy (TMR) scheme. We evaluate the proposed technique on timing-independent and timing-dependent errors induced by permanent and transient faults. In comparison with unranked selective fault tolerance approach, we demonstrate a) a similar error coverage with a 39.7% average reduction of the area overhead or b) a 86.9% average error coverage improvement for a similar area overhead. For the same area overhead case, we observe an error coverage improvement of 53.1% and 53.5% against permanent stuck-at and transition faults, respectively, and an average error coverage improvement of 151.8% and 89.0% against timing-dependent and timing-independent transient faults, respectively. Compared to TMR, the proposed technique achieves an area and power overhead reduction of 145.8% to 182.0%

Inter- and intra-observer variability analysis of completely automated cIMT measurement software (AtheroEdge™) and its benchmarking against commercial ultrasound scanner and expert Readers

The purpose of this study was to evaluate the measurement error and inter- and intra-observer variability of completely off-line automated and semi-automated carotid intima-media thickness (cIMT) measurement software (AtheroEdge™).Two hundred carotid ultrasound images from 50 asymptomatic women were analyzed. AtheroEdge™ was benchmarked against a commercial system (Syngo, Siemens) using automated and semi-automated modes. The measurement error and inter- and intra-observer variability of AtheroEdge™ were tested using three readings.The measurement error of AtheroEdge™ compared to the commercial software was 0.002±0.019. mm (r=0.99) in the automated mode and -0.001±0.004. mm in the semi-automated mode (r=0.99). The measurement error of AtheroEdge™ compared to the mean value of the three expert Readers (cIMT bias) for the automated and semi-automated methods was -0.0004±0.158. mm and -0.008±0.157. mm, respectively. The Figure-of-Merit was 99.8% and 99.9% when compared to the commercial ultrasound scanner (using the automated and semi-automated method, respectively) and was 99.9% and 98.9% when compared to the mean value of the three expert Readers. Regarding inter- and intra-observer variability, the intra-class correlation coefficient of the three independent users using the semi-automated AtheroEdge™ was 0.98.AtheroEdge™ showed a measurement performance comparable to the commercial ultrasound scanner software and the expert Readers' tracings. AtheroEdge™ belongs to a class of automated systems that could find application in processing large datasets for common carotid arteries, avoiding subjectivity in cIMT measurement

COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis

To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19

A UK wide cohort study describing management and outcomes for infants with surgical Necrotising Enterocolitis

The Royal College of Surgeons have proposed using outcomes from necrotising enterocolitis (NEC) surgery for revalidation of neonatal surgeons. The aim of this study was therefore to calculate the number of infants in the UK/Ireland with surgical NEC and describe outcomes that could be used for national benchmarking and counselling of parents. A prospective nationwide cohort study of every infant requiring surgical intervention for NEC in the UK was conducted between 01/03/13 and 28/02/14. Primary outcome was mortality at 28-days. Secondary outcomes included discharge, post-operative complication, and TPN requirement. 236 infants were included, 43(18%) of whom died, and eight(3%) of whom were discharged prior to 28-days post decision to intervene surgically. Sixty infants who underwent laparotomy (27%) experienced a complication, and 67(35%) of those who were alive at 28 days were parenteral nutrition free. Following multi-variable modelling, presence of a non-cardiac congenital anomaly (aOR 5.17, 95% CI 1.9-14.1), abdominal wall erythema or discolouration at presentation (aOR 2.51, 95% CI 1.23-5.1), diagnosis of single intestinal perforation at laparotomy (aOR 3.1 95% CI 1.05-9.3), and necessity to perform a clip and drop procedure (aOR 30, 95% CI 3.9-237) were associated with increased 28-day mortality. These results can be used for national benchmarking and counselling of parents

Delirium risk screening and haloperidol prophylaxis program in hip fracture patients is a helpful tool in identifying high-risk patients, but does not reduce the incidence of delirium

Background: Delirium in patients with hip fractures lead to higher morbidity and mortality. Prevention in high-risk patients by prescribing low dose haloperidol is currently under investigation. Methods. This prospective cohort surveillance assessed hip fracture patients for risk of developing a delirium with the Risk Model for Delirium (RD) score. High-risk patients (score ≥5 points) were treated with a prophylactic low-dose of haloperidol according to hospital protocol. Primary outcome was delirium incidence. Secondary outcomes were differences between high- and low-risk patients in delirium, length of stay (LOS), return to pre-fracture living situation and mortality. Logistic regression analysis was performed with age, ASA-classification, known dementia, having a partner, type of fracture, institutional residence and psychotropic drug use as possible confounders. Results: 445 hip fracture patients aged 65 years and older were admitted from January 2008 to December 2009. The RD-score was completed in 378 patients, 173 (45.8%) high-risk patients were treated with prophylactic medication. Sensitivity was 71.6%, specificity 63.8% and the negative predictive value (NPV) of a score < 5 was 85.9%. Delirium incidence (27.0%) was not significantly different compared to 2007 (27.8%) 2006 (23.9%) and 2005 (29.0%) prior to implementation of the RD- protocol. Logistic regression analysis showed that high-risk patients did have a significant higher delirium incidence (42.2% vs. 14.1%, OR 4.1, CI 2.43-7.02). They were more likely to be residing at an alternative living situation after 3 months (62.3% vs. 17.0%, OR 6.57, CI 3.23-13.37) and less likely to be discharged from hospital before 10 days (34.9% vs. 55.9%, OR 1.63, CI 1.03-2.59). Significant independent risk factors for a delirium were a RD-score 5 (OR 4.13, CI 2.43-7.02), male gender (OR 1.93, CI 0.99-1.07) and age (OR 1.03, CI 0.99-1.07). Conclusions: Introducing the delirium prevention protocol did not reduce delirium incidence. The RD-score did identify patients with a high risk to develop a delirium. This high-risk group had a longer LOS and returned to pre-fracture living situation less often. The NPV of a score < 5 was high, as it should be for a screening instrument. Concluding, the RD-score is a useful tool to identify patients with poorer outcome

SARS-CoV-2 variant Alpha has a spike-dependent replication advantage over the ancestral B.1 strain in human cells with low ACE2 expression

Epidemiological data demonstrate that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) Alpha and Delta are more transmissible, infectious, and pathogenic than previous variants. Phenotypic properties of VOC remain understudied. Here, we provide an extensive functional study of VOC Alpha replication and cell entry phenotypes assisted by reverse genetics, mutational mapping of spike in lentiviral pseudotypes, viral and cellular gene expression studies, and infectivity stability assays in an enhanced range of cell and epithelial culture models. In almost all models, VOC Alpha spread less or equally efficiently as ancestral (B.1) SARS-CoV-2. B.1. and VOC Alpha shared similar susceptibility to serum neutralization. Despite increased relative abundance of specific sgRNAs in the context of VOC Alpha infection, immune gene expression in infected cells did not differ between VOC Alpha and B.1. However, inferior spreading and entry efficiencies of VOC Alpha corresponded to lower abundance of proteolytically cleaved spike products presumably linked to the T716I mutation. In addition, we identified a bronchial cell line, NCI-H1299, which supported 24-fold increased growth of VOC Alpha and is to our knowledge the only cell line to recapitulate the fitness advantage of VOC Alpha compared to B.1. Interestingly, also VOC Delta showed a strong (595-fold) fitness advantage over B.1 in these cells. Comparative analysis of chimeric viruses expressing VOC Alpha spike in the backbone of B.1, and vice versa, showed that the specific replication phenotype of VOC Alpha in NCI-H1299 cells is largely determined by its spike protein. Despite undetectable ACE2 protein expression in NCI-H1299 cells, CRISPR/Cas9 knock-out and antibody-mediated blocking experiments revealed that multicycle spread of B.1 and VOC Alpha required ACE2 expression. Interestingly, entry of VOC Alpha, as opposed to B.1 virions, was largely unaffected by treatment with exogenous trypsin or saliva prior to infection, suggesting enhanced resistance of VOC Alpha spike to premature proteolytic cleavage in the extracellular environment of the human respiratory tract. This property may result in delayed degradation of VOC Alpha particle infectivity in conditions typical of mucosal fluids of the upper respiratory tract that may be recapitulated in NCI-H1299 cells closer than in highly ACE2-expressing cell lines and models. Our study highlights the importance of cell model evaluation and comparison for in-depth characterization of virus variant-specific phenotypes and uncovers a fine-tuned interrelationship between VOC Alpha- and host cell-specific determinants that may underlie the increased and prolonged virus shedding detected in patients infected with VOC Alpha