III-V Nanowire MOSFET High-Frequency Technology Platform

This thesis addresses the main challenges in using III-V nanowireMOSFETs for high-frequency applications by building a III-Vvertical nanowire MOSFET technology library. The initial devicelayout is designed, based on the assessment of the current III-V verticalnanowire MOSFET with state-of-the-art performance. The layout providesan option to scale device dimensions for the purpose of designing varioushigh-frequency circuits. The nanowire MOSFET device is described using1D transport theory, and modeled with a compact virtual source model.Device assessment is performed at high frequencies, where sidewall spaceroverlaps have been identified and mitigated in subsequent design iterations.In the final stage of the design, the device is simulated with fT > 500 GHz,and fmax > 700 GHz.Alongside the III-V vertical nanowire device technology platform, adedicated and adopted RF and mm-wave back-end-of-line (BEOL) hasbeen developed. Investigation into the transmission line parameters revealsa line attenuation of 0.5 dB/mm at 50 GHz, corresponding to state-ofthe-art values in many mm-wave integrated circuit technologies. Severalkey passive components have been characterized and modeled. The deviceinterface module - an interconnect via stack, is one of the prominentcomponents. Additionally, the approach is used to integrate ferroelectricMOS capacitors, in a unique setting where their ferroelectric behavior iscaptured at RF and mm-wave frequencies.Finally, circuits have been designed. A proof-of-concept circuit, designedand fabricated with III-V lateral nanowire MOSFETs and mm-wave BEOL, validates the accuracy of the BEOL models, and the circuit design. Thedevice scaling is shown to be reflected into circuit performance, in aunique device characterization through an amplifier noise-matched inputstage. Furthermore, vertical-nanowire-MOSFET-based circuits have beendesigned with passive feedback components that resonate with the devicegate-drain capacitance. The concept enables for device unilateralizationand gain boosting. The designed low-noise amplifiers have matching pointsindependent on the MOSFET gate length, based on capacitance balancebetween the intrinsic and extrinsic capacitance contributions, in a verticalgeometry. The proposed technology platform offers flexibility in device andcircuit design and provides novel III-V vertical nanowire MOSFET devicesand circuits as a viable option to future wireless communication systems

A study of a flexible fiber model and its behavior in DNS of turbulent channel flow

The dynamics of individual flexible fibers in a turbulent flow field have been analyzed, varying their initial position, density and length. A particlelevel fiber model has been integrated into a general-purpose, open source Computational Fluid Dynamics (CFD) code. The fibers are modeled as chains of cylindrical segments connected by ball and socket joints. The equations of motion of the fibers contain the inertia of the segments, the contributions from hydrodynamic forces and torques, and the connectivity forces at the joints. Direct Numerical Simulation (DNS) of the incompressible Navier–Stokes equations is used to describe the fluid flow in a plane channel and a one-way coupling is considered between the fibers and the fluid phase. We investigate the translational motion of fibers by considering the mean square displacement of their trajectories. We find that the fiber motion is primarily governed by velocity correlations of the flow fluctuations. In addition, we show that there is a clear tendency of the thread-like fibers to evolve into complex geometrical configurations in a turbulent flow field, in fashion similar to random conformations of polymer strands subjected to thermal fluctuations in a suspension. Finally, we show that fiber inertia has a significant impact on reorientation time-scales of fibers suspended in a turbulent flow field

Particle-level simulations of flocculation in a fiber suspension flowing through a diffuser

We investigate flocculation in dilute suspensions of rigid, straight fibers in a decelerating flow field of a diffuser. We carry out numerical studies using a particle-level simulation technique that takes into account the fiber inertia and the non-creeping fiber-flow interactions. The fluid flow is governed by the Reynolds-averaged Navier-Stokes equations with the standard k-omega eddy-viscosity turbulence model. A one-way coupling between the fibers and the flow is considered with a stochastic model for the fiber dispersion due to turbulence. The fibers interact through short-range attractive forces that cause them to aggregate into flocs when fiber-fiber collisions occur. We show that ballistic deflection of fibers greatly increases the flocculation in the diffuser. The inlet fiber kinematics and the fiber inertia are the main parameters that affect fiber flocculation in the pre-diffuser region

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Low-Temperature Front-Side BEOL Technology with Circuit Level Multiline Thru-Reflect-Line Kit for III-V MOSFETs on Silicon

A multiline Thru-Reflect-Line (mTRL) calibration and parasitic pad removal kit is presented, intended for mm-wave III-V nanowire MOSFET characterization. Multiline TRL is implemented in a low-temperature BEOL process with substrate decoupled microstrip transmission lines. The transmission line characteristic impedance needed for accurate mTRL calibration is modelled. Simulated transmission line parameters show a good fit with measured transmission line data, including line characteristic impedance variation. Line loss less than 0.5 dB/mm up to 50 GHz is obtained. Finally, interconnect via section is calibrated and modelled, showing mTRL's ability to obtain small parasitic parameters

Design of III-V Vertical Nanowire MOSFETs for Near-Unilateral Millimeter-Wave Operation

Vertical nanowire MOSFETs exhibit asymmetric gate capacitances, allowing for their independent engineering to improve device high frequency performance. Minimizing gate-drain parasitic capacitance with the use of a vertical sidewall spacer enables universal feedback neutralization and a unilateral circuit design. For vertical spacer thickness above 20 nm, the gate-drain capacitance variability is reduced. Device technology is verified by simulation of 60 GHz three-stage low-noise amplifier. The amplifier exhibits 10 dB gain and 6.9 dB noise figure. The noise figure can be further reduced to 5.9 dB by combining several feedback techniques. The use of capacitance minimization reduces circuit sensitivity to device variation, demonstrating the potential of this technology in implementation of mm-wave communication and sensing systems