Digital Detection of Oxide Breakdown and Life-Time Extension in Submicron CMOS Technology

An approach is introduced to extend the lifetime of high-voltage analog circuits in CMOS technologies based on redundancy, like that known for DRAMS. A large power transistor is segmented into N smaller ones in parallel. If a sub-transistor is broken, it is removed automatically from the compound transistor. The principleis demonstrated in an RF CMOS Power Amplifier (PA) in standard 1.2V 90nm CMOS

45° light turning mirrors for hybrid integration of silica optical waveguides and photo-detectors

For hybrid integration of an optical chip with an electronic chip with photo diodes and electronic processing, light must be coupled from the optical chip to the electronic chip. This paper presents a method to fabricate metal-free 45° quasi-total internal reflecting mirrors in optical chips that enable 90° out-of-plane light coupling between flip-chip bonded chips. This method is fully compatible with fabrication of conventional optical chips. The mirrors are created using anisotropic etching of 45° facets in a Si substrate followed by fabrication of optical structures. After removal of the mirror-defining Si structures by isotropic etching, the obtained air-optical structure interface directs the output of the waveguides to out-of-plane photo detectors that are mounted flip-chip on the optical chip. Simulations show a reflection efficiency of 72.3 %, while experimentally 47% was measured on a not fully optimized first batch

An audio FIR-DAC in a BCD process for high power Class-D amplifiers

A 322 coefficient semi-digital FIR-DAC using a 1-bit PWM input signal was designed and implemented in a high voltage, audio power bipolar CMOS DMOS (BCD) process. This facilitates digital input signals for an analog class-D amplifier in BCD. The FIR-DAC performance depends on the ISI-resistant nature of this PWM-signal. An impulse response with only positive coefficients was chosen, because of its resistance to deadzone and mismatch. With a DAC current of 0.5 mA, the dynamic range is 111 dB (A-weighted), with SINAD = 103 dB (A-weighted). The current consumption is 1mA for the analog part and 4.8 mA for the digital part. The power consumption is 29 mW at V/sub dd/ = 5 V and the chip area is 2 mm/sup 2/ including the reference diode that can be shared by more channels

Employer Attitudes towards Peak Hour Avoidance

Peak Hour Avoidance is a relatively new Dutch mobility management measure. To reduce congestion frequent car drivers are given a financial reward for reducing the proportion of trips that they make during peak hours on a specific motorway section. Although previous studies show that employers are not eager to support mobility management measures, employers are nevertheless an important stakeholder. They can provide their employees with alternatives such as other travel times, work locations or travel modes and encourage their use. This paper investigates the attitudes of Dutch employers towards Peak Hour Avoidance. Exploring the factors that influence these attitudes may help to fully utilise employer support. The data from 103 employers were collected through a web questionnaire. A structural equation model on the employer support for Peak Hour Avoidance was estimated. The results demonstrate that the size of the organisation and sector only have an indirect effect on the support for Peak Hour Avoidance. Results reveal that most support for Peak Hour Avoidance can be expected from organisations who feel responsible for influencing the commuting behaviour of employees, that have human resource managers with a positive attitude towards Peak Hour Avoidance, with flexible working times and that have already implemented mobility management measures. The largest contribution to PHA that can be expected from employers is providing employees with flexible working times and encouraging employees to fully utilise this option as an alternative for driving in peak hours. This would not only be beneficial for PHA but for a wide range of mobility management initiatives as well

Discrepancy between self-perceived mycophenolic acid-associated diarrhea and stool water content after kidney transplantation

BACKGROUND: Diarrhea is a well-known side effect of mycophenolic acid (MPA) use in kidney transplant recipients (KTRs). It is unknown whether self-reported diarrhea using the Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) corresponds to stool water content and how both relate to MPA usage. METHODS: MTSOSD-59R questionnaires filled out by 700 KTRs from the TransplantLines Biobank and Cohort Study(NCT03272841) were analyzed and compared with stool water content. Stool samples(N=345) were freeze-dried and a water content ≥80% was considered diarrhea. RESULTS: Self-perceived diarrhea was reported by 46%, while stool water content ≥80% was present in 23% of KTRs. MPA use was not associated with self-perceived diarrhea (odds ratio(OR) 1.32; 95% confidence interval(CI), 0.87-1.99, P=0.2), while it was associated with stool water content ≥80% (OR 2.88; 95%CI, 1.41-5.89, P=0.004), independent of potential confounders. Adjustment for prior MPA discontinuation because of severe diarrhea, uncovered an association between MPA use and self-perceived diarrhea (OR 1.80; 95%CI, 1.13-2.89, P=0.01). CONCLUSIONS: These results suggest that reporting bias could add to the discrepancy between both methods for diarrhea assessment. We recommend use of objective biomarkers or more extensive questionnaires which assess information on stool frequency and stool consistency, to investigate post-transplantation diarrhea

Esophageal Endosonography for the Diagnosis of Intrapulmonary Tumors:A Systematic Review and Meta-Analysis

BACKGROUND: Biopsy-based diagnosis in patients with paraesophageal intrapulmonary tumors suspected of lung cancer is crucial for adequate treatment planning. OBJECTIVE: To evaluate the performance of transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the diagnosis of intrapulmonary tumors located near or adjacent to the esophagus. METHODS: We performed a systematic review (PROSPERO, CRD42016033737) and searched MEDLINE, Embase, BIOSIS Previews, and Web of Science on September 22, 2016, without date or language restrictions. We included studies that evaluated the yield and/or sensitivity of EUS-FNA for diagnosing intrapulmonary tumors. Yield was defined as the number of patients in whom EUS-FNA made a biopsy-proven diagnosis (malignant or nonmalignant) relative to the total number of patients on whom EUS-FNA was performed. Sensitivity was defined as the number of patients in whom EUS-FNA made a biopsy-proven diagnosis of malignancy relative to the total number of patients in whom the tumor was found to be malignant. We performed a random-effects meta-analysis. RESULTS: Of 3,320 search results, 11 studies were included. Ten had a high risk of bias. The total number of patients was 313; the proportion of patients with malignancy ranged from 87 to 100% across these studies. The average yield was 0.90 (95% CI 0.82-0.95) and the average sensitivity was 0.92 (0.83-0.96). In the subgroup of prospective studies (n = 3), the average yield was 0.80 (0.56-0.93) and the average sensitivity was 0.83 (0.58-0.95). EUS-FNA-induced complications were reported for 5/256 patients (2.0%) for whom this information was available. CONCLUSIONS: Although the number of high-quality studies is limited, these findings suggest that EUS-FNA is safe and has a high yield for diagnosing intrapulmonary tumors

Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomised controlled trial

Copyright @ Queen’s Printer and Controller of HMSO 2012. This work was produced by Sharples et al. under the terms of a commissioning contract issued by the Secretary of State for Health.Objective: To assess the clinical effectiveness and cost-effectiveness of endosonography (followed by surgical staging if endosonography was negative), compared with standard surgical staging alone, in patients with non-small cell lung cancer (NSCLC) who are otherwise candidates for surgery with curative intent. Design: A prospective, international, open-label, randomised controlled study, with a trialbased economic analysis. Setting: Four centres: Ghent University Hospital, Belgium; Leuven University Hospitals,Belgium; Leiden University Medical Centre, the Netherlands; and Papworth Hospital, UK. Participants: Inclusion criteria: known/suspected NSCLC, with suspected mediastinal lymph node involvement; otherwise eligible for surgery with curative intent; clinically fit for endosonography and surgery; and no evidence of metastatic disease. Exclusion criteria: previous lung cancer treatment; concurrent malignancy; uncorrected coagulopathy; and not suitable for surgical staging. Interventions: Study patients were randomised to either surgical staging alone (n = 118) or endosonography followed by surgical staging if endosonography was negative (n = 123). Endosonography diagnostic strategy used endoscopic ultrasound-guided fine-needle aspiration combined with endobronchial ultrasound-guided transbronchial needle aspiration, followed by surgical staging if these tests were negative. Patients with no evidence of mediastinal metastases or tumour invasion were referred for surgery with curative intent. If evidence of malignancy was found, patients were referred for chemoradiotherapy. Main outcome measures: The main clinical outcomes were sensitivity (positive diagnostic test/nodal involvement during any diagnostic test or thoracotomy) and negative predictive value (NPV) of each diagnostic strategy for the detection of N2/N3 metastases, unnecessary thoracotomy and complication rates. The primary economic outcome was cost–utility of the endosonography strategy compared with surgical staging alone, up to 6 months after randomisation, from a UK NHS perspective. Results: Clinical and resource-use data were available for all 241 patients, and complete utilities were available for 144. Sensitivity for detecting N2/N3 metastases was 79% [41/52; 95% confidence interval (CI) 66% to 88%] for the surgical arm compared with 94% (62/66; 95% CI 85% to 98%) for the endosonography strategy (p = 0.02). Corresponding NPVs were 86% (66/77; 95% CI 76% to 92%) and 93% (57/61; 95% CI 84% to 97%; p = 0.26). There were 21/118 (18%) unnecessary thoracotomies in the surgical arm compared with 9/123 (7%) in the endosonography arm (p = 0.02). Complications occurred in 7/118 (6%) in the surgical arm and 6/123 (5%) in the endosonography arm (p = 0.78): one pneumothorax related to endosonography and 12 complications related to surgical staging. Patients in the endosonography arm had greater EQ-5D (European Quality of Life-5 Dimensions) utility at the end of staging (0.117; 95% CI 0.042 to 0.192; p = 0.003). There were no other significant differences in utility. The main difference in resource use was the number of thoracotomies: 66% patients in the surgical arm compared with 53% in the endosonography arm. Resource use was similar between the groups in all other items. The 6-month cost of the endosonography strategy was £9713 (95% CI £7209 to £13,307) per patient versus £10,459 (£7732 to £13,890) for the surgical arm, mean difference £746 (95% CI –£756 to £2494). The mean difference in quality-adjusted life-year was 0.015 (95% CI –0.023 to 0.052) in favour of endosonography, so this strategy was cheaper and more effective. Conclusions: Endosonography (followed by surgical staging if negative) had higher sensitivity and NPVs, resulted in fewer unnecessary thoracotomies and better quality of life during staging, and was slightly more effective and less expensive than surgical staging alone. Future work could investigate the need for confirmatory mediastinoscopy following negative endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), the diagnostic accuracy of EUS-FNA or EBUS-TBNA separately and the delivery of both EUSFNA or EBUS-TBNA by suitably trained chest physicians.This project was funded by the NIHR Health Technology Assessment programm

Imaging the pulmonary extracellular matrix

The pulmonary extracellular matrix (ECM) plays an important role in the structure and function of the lung. In many respiratory diseases the profile of the ECM reflects pathological changes. The capacity to visualize the ECM and its alterations is of considerable importance to facilitate a better understanding of pulmonary diseases and eventually augment therapeutic solutions. This short review summarizes the current and novel possibilities for imaging the pulmonary ECM by the use of computed tomography (CT), optical coherence tomography (OCT), confocal laser endomicroscopy (CLE) and molecular imaging. While not all these techniques are as yet implemented in standard clinical practice, we address their main features along with the key possibilities for the future

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients:Results From the TransplantLines Biobank and Cohort Study

RATIONALE &amp; OBJECTIVE: Prior studies report that the use of proton-pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients (KTR). Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population.STUDY DESIGN: Cross-sectional study.SETTING &amp; PARTICIPANTS: KTR (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study.EXPOSURE: PPI use, PPI type, PPI dosage, and duration of PPI use.OUTCOMES: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire.ANALYTICAL APPROACH: Logistic and linear regression.RESULTS: We included 937 KTR (mean age 56±13 years, 39% female) at a median of 3 [1-10] years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95%CI 2.18 to 5.85, p&lt;0.001), a higher risk of severe fatigue (OR 2.05, 95%CI 1.48 to 2.84, p&lt;0.001), lower physical HRQoL (regression coefficient -8.54, 95%CI -11.54 to -5.54, p&lt;0.001), and lower mental HRQoL (regression coefficient -4.66, 95%CI -7.15 to -2.17, p&lt;0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose-dependent. Duration of PPI exposure was only associated with fatigue severity.LIMITATIONS: Residual confounding and inability to assess causal relationships CONCLUSIONS: PPI use is independently associated with fatigue and lower HRQoL among KTR. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among KTR. Further studies examining the effect of PPI exposure in this population are warranted.</p