Analysis and design of an efficient, fully integrated 1-8GHz traveling wave power amplifier in 180nm CMOS

Traveling wave amplifiers (TWAs) offer the advantage of broadband amplification and a closed set of equations that allow deriving the RF gain by means of treating TWAs as discrete transmission line approximations. Up to now, however, the significant losses associated with CMOS integrated inductors have been neglected. This work presents a new approach for determining the transmission line losses and phase constants that will bring about an enhanced gain prediction accuracy. The theory is verified by means of a realized design example. The working principle of the integrated DC supply inductor is discussed, whose performance is based on the inductors self-resonance effect. When applying a supply voltage Vdd of 2.4V, the measured compression point P1dB and the power added efficiency PAE at 2.4GHz amount to 16.9dBm and 19.6%, respectively. At 5.5GHz, a value of 16.6dBm for P1dB and an associated PAE of 13.9% are achieved. The peak RF gain for these output power values reaches 11dB, and values greater than 8dB are obtained up to 7GH

Adaptive optical interconnects: The ADDAPT project

Existing optical networks are driven by dynamic user and application demands but operate statically at their maximum performance. Thus, optical links do not offer much adaptability and are not very energy-effcient. In this paper a novel approach of implementing performance and power adaptivity from system down to optical device, electrical circuit and transistor level is proposed. Depending on the actual data load, the number of activated link paths and individual device parameters like bandwidth, clock rate, modulation format and gain are adapted to enable lowering the components supply power. This enables exible energy-efficient optical transmission links which pave the way for massive reductions of CO2 emission and operating costs in data center and high performance computing applications. Within the FP7 research project Adaptive Data and Power Aware Transceivers for Optical Communications (ADDAPT) dynamic high-speed energy-efficent transceiver subsystems are developed for short-range optical interconnects taking up new adaptive technologies and methods. The research of eight partners from industry, research and education spanning seven European countries includes the investigation of several adaptive control types and algorithms, the development of a full transceiver system, the design and fabrication of optical components and integrated circuits as well as the development of high-speed, low-loss packaging solutions. This paper describes and discusses the idea of ADDAPT and provides an overview about the latest research results in this field

Free-Circulating Methylated DNA in Blood for Diagnosis, Staging, Prognosis, and Monitoring of Head and Neck Squamous Cell Carcinoma Patients: An Observational Prospective Cohort Study

Abstract BACKGROUND Circulating cell-free DNA methylation testing in blood has recently received regulatory approval for screening of colorectal cancer. Its application in other clinical settings, including staging, prognosis, prediction, and recurrence monitoring is highly promising, and of particular interest in head and neck squamous cell carcinomas (HNSCCs) that represent a heterogeneous group of cancers with unsatisfactory treatment guidelines. METHODS Short stature homeobox 2 (SHOX2) and septin 9 (SEPT9) DNA methylation in plasma from 649 prospectively enrolled patients (training study: 284 HNSCC/122 control patients; testing study: 141 HNSCC/102 control patients) was quantified before treatment and longitudinally during surveillance. RESULTS In the training study, 59% of HNSCC patients were methylation-positive at 96% specificity. Methylation levels correlated with tumor and nodal category (P &amp;lt; 0.001). Initially increased methylation levels were associated with a higher risk of death [SEPT9: hazard ratio (HR) = 5.27, P = 0.001; SHOX2: HR = 2.32, P = 0.024]. Disease recurrence/metastases were detected in 47% of patients up to 377 days earlier compared to current clinical practice. The onset of second cancers was detected up to 343 days earlier. In the testing study, sensitivity (52%), specificity (95%), prediction of overall survival (SEPT9: HR = 2.78, P = 0.022; SHOX2: HR = 2.50, P = 0.026), and correlation with tumor and nodal category (P &amp;lt;0.001) were successfully validated. CONCLUSIONS Methylation testing in plasma is a powerful diagnostic tool for molecular disease staging, risk stratification, and disease monitoring. Patients with initially high biomarker levels might benefit from intensified treatment and posttherapeutic surveillance. The early detection of a recurrent/metastatic disease or a second malignancy could lead to an earlier consecutive treatment, thereby improving patients' outcomes. </jats:sec

Irinotecan and temozolomide in combination with dasatinib and rapamycin versus irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma (RIST-rNB-2011): a multicentre, open-label, randomised, controlled, phase 2 trial

Background Neuroblastoma is the most common extracranial solid tumour in children. Relapsed or refractory neuroblastoma is associated with a poor outcome. We assessed the combination of irinotecan–temozolomide and dasatinib–rapamycin (RIST) in patients with relapsed or refractory neuroblastoma. Methods The multicentre, open-label, randomised, controlled, phase 2, RIST-rNB-2011 trial recruited from 40 paediatric oncology centres in Germany and Austria. Patients aged 1–25 years with high-risk relapsed (defined as recurrence of all stage IV and MYCN amplification stages, after response to treatment) or refractory (progressive disease during primary treatment) neuroblastoma, with Lansky and Karnofsky performance status at least 50%, were assigned (1:1) to RIST (RIST group) or irinotecan–temozolomide (control group) by block randomisation, stratified by MYCN status. We compared RIST (oral rapamycin [loading 3 mg/m2 on day 1, maintenance 1 mg/m2 on days 2–4] and oral dasatinib [2 mg/kg per day] for 4 days with 3 days off, followed by intravenous irinotecan [50 mg/m2 per day] and oral temozolomide [150 mg/m2 per day] for 5 days with 2 days off; one course each of rapamycin–dasatinib and irinotecan–temozolomide for four cycles over 8 weeks, then two courses of rapamycin–dasatinib followed by one course of irinotecan–temozolomide for 12 weeks) with irinotecan–temozolomide alone (with identical dosing as experimental group). The primary endpoint of progression-free survival was analysed in all eligible patients who received at least one course of therapy. The safety population consisted of all patients who received at least one course of therapy and had at least one post-baseline safety assessment. This trial is registered at ClinicalTrials.gov, NCT01467986, and is closed to accrual. Findings Between Aug 26, 2013, and Sept 21, 2020, 129 patients were randomly assigned to the RIST group (n=63) or control group (n=66). Median age was 5·4 years (IQR 3·7–8·1). 124 patients (78 [63%] male and 46 [37%] female) were included in the efficacy analysis. At a median follow-up of 72 months (IQR 31–88), the median progression-free survival was 11 months (95% CI 7–17) in the RIST group and 5 months (2–8) in the control group (hazard ratio 0·62, one-sided 90% CI 0·81; p=0·019). Median progression-free survival in patients with amplified MYCN (n=48) was 6 months (95% CI 4–24) in the RIST group versus 2 months (2–5) in the control group (HR 0·45 [95% CI 0·24-0·84], p=0·012); median progression-free survival in patients without amplified MYCN (n=76) was 14 months (95% CI 9–7) in the RIST group versus 8 months (4–15) in the control group (HR 0·84 [95% CI 0·51–1·38], p=0·49). The most common grade 3 or worse adverse events were neutropenia (54 [81%] of 67 patients given RIST vs 49 [82%] of 60 patients given control), thrombocytopenia (45 [67%] vs 41 [68%]), and anaemia (39 [58%] vs 38 [63%]). Nine serious treatment-related adverse events were reported (five patients given control and four patients given RIST). There were no treatment-related deaths in the control group and one in the RIST group (multiorgan failure). Interpretation RIST-rNB-2011 demonstrated that targeting of MYCN-amplified relapsed or refractory neuroblastoma with a pathway-directed metronomic combination of a multkinase inhibitor and an mTOR inhibitor can improve progression-free survival and overall survival. This exclusive efficacy in MYCN-amplified, relapsed neuroblastoma warrants further investigation in the first-line setting

Analysis and design of an efficient, fully integrated 1–8 GHz traveling wave power amplifier in 180 nm CMOS

ISSN:1759-0787ISSN:1759-079

Predictors for Outcome and Complications Related to Urinary Diversion

Background/Aim: Predictors for complications such as insufficiency of intestinal anastomosis in urinary diversion and other risk factors are not well defined. We aimed to elucidate predictive factors for complications in urinary diversions based on preoperative comorbidities and major complications. A special focus was set on anastomosis insufficiency as a major complication. Patients and Methods: Preoperative comorbidities, postoperative complications, duration of hospital stay, and follow-up were analyzed in 317 patients with urinary diversion. The impact of preoperative comorbidities on diversion types was described and quantified as defined by the age-adjusted Charlson Comorbidity Index. Results: Overall, 14.8% of patients showed anastomosis-related complications, most within the ileal conduit group (15.9% in the cohort). Severe complications (Clavien-Dindo Classification Score >IIIa) were found in smokers (p=0.046), and in patients with vascular diseases (p=0.007), a high American Society of Anaesthesiologists (ASA)-score (p=0.047), a R1-(p=0.009), as well as a pN1 (p=0.007) status. Conclusion: Several independent predictors for several postoperative complications in urinary diversions were identified, which were independent of the diversion method

Prognostic role of TSPAN1, KIAA1324 and ESRP1 in prostate cancer

The aim of this study was to validate prostate cancer-associated genes on transcript level and to assess the prognostic value of the most promising markers by immunohistochemistry. Based on differentially expressed genes found in a previous study, 84 genes were further validated using mRNA expression data and follow-up information from the Cancer Genome Atlas (TCGA) prostate cancer cohort (n = 497). Immunohistochemistry was used for validation of three genes in an independent, clinically annotated prostatectomy patient cohort (n = 175) with biochemical relapse as endpoint. Also, associations with clinicopathological variables were evaluated. Eleven protein-coding genes from the list of 84 genes were associated with biochemical recurrence-free survival on mRNA expression level in multivariate Cox-analyses. Three of these genes (TSPAN1, ESRP1 and KIAA1324) were immunohistochemically validated using an independent cohort of prostatectomy patients. Both ESRP1 and KIAA1324 were independently associated with biochemical recurrence-free survival. TSPAN1 was univariately prognostic but failed significance on multivariate analysis, probably due to its strong correlation with high Gleason scores. Multistep filtering using the publicly available TCGA cohort, data of an earlier expression profiling study which profiled 3023 cancer-associated transcripts in 42 primary prostate cancer cases, identified two novel candidate prognostic markers (ESRP1 and KIAA1324) of primary prostate cancer for further study

Prognostic role of TSPAN1, KIAA1324 and ESRP1 in prostate cancer

The aim of this study was to validate prostate cancer-associated genes on transcript level and to assess the prognostic value of the most promising markers by immunohistochemistry. Based on differentially expressed genes found in a previous study, 84 genes were further validated using mRNA expression data and follow-up information from the Cancer Genome Atlas (TCGA) prostate cancer cohort (n = 497). Immunohistochemistry was used for validation of three genes in an independent, clinically annotated prostatectomy patient cohort (n = 175) with biochemical relapse as endpoint. Also, associations with clinicopathological variables were evaluated. Eleven protein-coding genes from the list of 84 genes were associated with biochemical recurrence-free survival on mRNA expression level in multivariate Cox-analyses. Three of these genes (TSPAN1, ESRP1 and KIAA1324) were immunohistochemically validated using an independent cohort of prostatectomy patients. Both ESRP1 and KIAA1324 were independently associated with biochemical recurrence-free survival. TSPAN1 was univariately prognostic but failed significance on multivariate analysis, probably due to its strong correlation with high Gleason scores. Multistep filtering using the publicly available TCGA cohort, data of an earlier expression profiling study which profiled 3023 cancer-associated transcripts in 42 primary prostate cancer cases, identified two novel candidate prognostic markers (ESRP1 and KIAA1324) of primary prostate cancer for further study

Comparison of Myocardial Remodeling between Cryoinfarction and Reperfused Infarction in Mice

Myocardial infarction is associated with inflammatory reaction leading to tissue remodeling. We compared tissue remodeling between cryoinfarction (cMI) and reperfused myocardial infarction (MI) in order to better understand the local environment where we apply cell therapies. Models of closed-chest one-hour ischemia/reperfusion MI and cMI were used in C57/Bl6-mice. The reperfused MI showed rapid development of granulation tissue and compacted scar formation after 7 days. In contrast, cMI hearts showed persistent cardiomyocyte debris and cellular infiltration after 7 days and partially compacted scar formation accompanied by persistent macrophages and myofibroblasts after 14 days. The mRNA of proinflammatory mediators was transiently induced in MI and persistently upregulated in cMI. Tenascin C and osteopontin-1 showed delayed induction in cMI. In conclusion, the cryoinfarction was associated with prolonged inflammation and active myocardial remodeling when compared to the reperfused MI. These substantial differences in remodeling may influence cellular engraftment and should be considered in cell therapy studies