In this paper, we are presenting a noise modeling technique in fully depleted (FD) SOI MOSFET. Starting from a physical compact model which allows us to capture the physics in such devices, an ...original microscopic noise model, suitable to calculate the noise performance of any field effect transistor, is developed. The method is applied to study the noise properties of FD SOI MOSFETs (0.25 μm physical gate length, 0.16 μm effective gate length); this includes a discussion at a microscopic level, the calculation of the usual
P,
R,
C parameters (close to the device physics) and of the noise performances, taking into account extrinsic elements. To conclude, a discussion related to the noise performances as a function of the down-scaling is proposed.
The dc and radio-frequency performance of 85-nm gate-length p-channel PtSi source/drain Schottky-barrier MOSFETs on two wafers with differing source/drain silicide anneal temperatures has been ...investigated. ON currents of 545 mA/ mm and transconductances of 640 mS/mm are presented for bias conditions based on recommendations by the International Technology Roadmap for Semiconductors. Devices receiving silicide anneals at lower temperatures exhibit higher drive currents and transconductances, which is attributed to a lower Schottky barrier between source and channel. Unity-gain cutoff frequencies of up to 71 GHz are measured, which is considerably higher than comparable doped source/drain pMOS devices reported in literature. Improved high-frequency performance is attributed to high transconductance and low capacitance.
Two different strategies for investigating the likely fate, after ingestion, of natural, bioactive berry constituents (anthocyanins and other non-nutritive flavonoids) are compared. A model of the ...human gastrointestinal tract (TIM-1) that mimicked the biological environment from the point of swallowing and ingestion through the duodenum, jejunum, and ileum (but not the colon) was used to monitor the stability and bioaccessibility of anthocyanins from both maqui berry and wild blueberry. TIM-1 revealed that most anthocyanins were bioaccessible between the second and third hours after intake. Alternatively, biolabeled anthocyanins and other flavonoids generated in vitro from berry and grape cell cultures were administered to in vivo (rodent) models, allowing measurement and tracking of the absorption and transport of berry constituents and clearance through the urinary tract and colon. The advantages and limitations of the alternative strategies are considered.
Evaluating the importance of electromagnetic (EM) coupling from through silicon vias (TSVs) has become crucial to the design of three-dimensional integrated circuits (3D-ICs). One of the most ...important parasitic contributions to signal propagation in 3D-ICs is the TSV capacitance. It is both frequency and bias dependent since a TSV is a metal-oxide-semiconductor (MOS) structure. In this work, anomalous TSV capacitance behavior after wafer thinning is reported and investigated by combining measurements and finite element (FEM) semiconductor simulations. Excellent agreement between models and experimental data confirms the origin of the anomalous TSV capacitance behavior: the presence of fixed charges in the back side (BS) passivation layer of the TSV after wafer thinning. In addition, a BS inversion layer can act as a conductive channel between neighboring vias, increasing the capacitive coupling between TSVs. Calibrated equivalent circuit models of the TSV in contact with a BS inversion layer are proposed for the first time in the context of 3D integration and validated.
Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the
Ataxin 10
gene. SCA10 ...patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilepsy. SCA10 expansions containing penta- and heptanucleotide interruption motifs, termed “ATCCT interruptions,” experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic seizures in one Mexican-American SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT interruptions confer a greater risk for developing seizures in these families. Notably, we find that the presence of repeat interruptions within the SCA10 expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in SCA10 repeat expansion indicates a significant risk for the epilepsy phenotype and should be considered during genetic counseling.
Abstract
BACKGROUND: TRK fusions are detected in less than 3% of CNS tumors. Given their rarity, there are limited data on the clinical course of these patients. METHODS: We contacted 166 oncology ...centers worldwide to retrieve data on patients with TRK fusion-driven CNS tumors. Data extracted included demographics, histopathology, NTRK gene fusion, treatment modalities and outcomes. Patients less than 18 years of age at diagnosis were included in this analysis. RESULTS: Seventy-three pediatric patients with TRK fusion-driven primary CNS tumors were identified. Median age at diagnosis was 2.4 years (range 0.0–17.8) and 60.2 % were male. NTRK2 gene fusions were found in 37 patients (50.7%), NTRK1 and NTRK3 aberrations were detected in 19 (26.0%) and 17 (23.3%), respectively. Tumor types included 38 high-grade gliomas (HGG; 52.1%), 20 low-grade gliomas (LGG; 27.4%), 4 embryonal tumors (5.5%) and 11 others (15.1%). Median follow-up was 46.5 months (range 3-226). During the course of their disease, a total of 62 (84.9%) patients underwent surgery with a treatment intent, 50 (68.5%) patients received chemotherapy, 35 (47.9%) patients received radiation therapy, while 34 (46.6%) patients received NTRK inhibitors (3 as first line treatment). Twenty-four (32.9%) had no progression including 9 LGG (45%) and 9 HGG (23.6%). At last follow-up, only one (5.6%-18 evaluable) patient with LGG died compared to 11 with HGG (35.5%-31 evaluable). For LGG the median progression-free survival (PFS) after the first line of treatment was 17 months (95% CI: 0.0-35.5) and median overall survival (OS) was not reached. For patients with HGG the median PFS was 30 months (95% CI: 11.9-48.1) and median OS was 182 months (95% CI 20.2-343.8). CONCLUSIONS: We report the largest cohort of pediatric patients with TRK fusion-driven primary CNS tumors. These results will help us to better understand clinical evolution and compare outcomes with ongoing clinical trials.
Abstract Background Clinical trials assessing antidepressant therapies typically include separate assessments of efficacy (benefit) and adverse events (risk). Global benefit–risk (GBR) assessment ...allows the simultaneous evaluation of both efficacy and adverse events. The objective was to compare the serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine and venlafaxine using GBR assessment. Methods Data were combined from two similarly designed, multicenter, randomized, double-blind, parallel group studies in which patients with major depressive disorder were randomized to either duloxetine 60 mg/day or venlafaxine extended release (XR) 150 mg/day (75 mg/day for the first 2 weeks) for a 6-week fixed dosing period followed by an additional 6 weeks of treatment in which the dose could be increased up to 120 mg/day for duloxetine and 225 mg/day for venlafaxine. Patients completing the study (or receiving study drug for 2 weeks or more) were eligible to enter a taper period where the dose of study drug was gradually reduced over 1–2 weeks prior to drug discontinuation. The primary outcome measure (defined a priori ) was the GBR comparison of duloxetine 60 mg/day and venlafaxine XR 150 mg/day after 6 weeks of treatment. In the GBR analysis, benefit was defined as remission at endpoint 17-item Hamilton Depression Rating Scale (HAMD17) ⩽ 7. Risk was defined by four categories: patients having either no adverse events (AEs), AEs with no severity rating greater than moderate, AEs with at least one severity rating of severe, or having discontinued with a reason of self-reported adverse event (regardless of any AE severity). Additional efficacy measures included HAMD17 total score and subscales, HAMA, CGI-S, and PGI-I. Safety and tolerability were assessed via analysis of reasons for discontinuation, treatment-emergent adverse events (TEAEs), discontinuation-emergent adverse events, and changes in vital signs, weight, and laboratory analytes. Results There were no significant differences between duloxetine 60 mg/day and venlafaxine 150 mg/day as measured by GBR assessment at the end of 6 weeks (−1.418 vs. −1.079, P = 0.217) or 12 weeks (−0.349 vs. −0.121, P = 0.440), nor were there significant differences between treatment groups on the majority of efficacy measures. Significantly more venlafaxine-treated patients (74.5%) completed 12 weeks of treatment compared with duloxetine-treated patients (64.8%, P = .006). Nausea was the most common treatment-emergent adverse event (TEAE) for both drugs, and was significantly higher with duloxetine 60 mg/day compared to venlafaxine 150 mg/day during the first 6 weeks of treatment (43.6% vs. 35.0%, P ⩽ 0.05). During the taper period, significantly more venlafaxine-treated patients reported discontinuation-emergent adverse events (DEAEs) than duloxetine-treated patients. From a safety perspective, significantly more venlafaxine-treated patients ( n = 4) than duloxetine-treated patients ( n = 0, P = .047) experienced sustained elevations of systolic blood pressure during the fixed dosing period. Otherwise, there were few significant differences in safety measures found between treatment groups during 6 and 12 weeks of therapy. Conclusions Duloxetine 60 mg/day and venlafaxine XR 150 mg/day have similar benefit–risk profiles on the basis of a comparison utilizing GBR assessment. The implications of the more subtle differences between these drugs, as well as for interpreting the GBR assessment, are discussed.
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