A Power-Efficient, Low-Distortion Variable Gain Amplifier Consisting of Coupled Differential Pairs

Abstract-A variable gain amplifier incorporating a plurality of coupled differential pairs has been designed in a bipolar technology. By applying variable offset voltages to these differential pairs, the overall gain of the system can be varied. The linear input region is inversely proportional to gain, making the amplifier very well suited for automatic gain control circuits. Furthermore, the gain of the proposed amplifier is 0-25 dB, the signal bandwidth is 35 MHz, and the output IP3 is 24-30 dBm. It operates from a 5-V power supply and dissipates 40 mW. The active chip area is 0.15 mm 2 in a 1-m bipolar technology

Luminosity- and morphology-dependent clustering of galaxies

How does the clustering of galaxies depend on their inner properties like morphological type and luminosity? We address this question in the mathematical framework of marked point processes and clarify the notion of luminosity and morphological segregation. A number of test quantities such as conditional mark-weighted two-point correlation functions are introduced. These descriptors allow for a scale-dependent analysis of luminosity and morphology segregation. Moreover, they break the degeneracy between an inhomogeneous fractal point set and actual present luminosity segregation. Using the Southern Sky Redshift Survey~2 (da Costa et al. 1998, SSRS2) we find both luminosity and morphological segregation at a high level of significance, confirming claims by previous works using these data (Benoist et al. 1996, Willmer et al. 1998). Specifically, the average luminosity and the fluctuations in the luminosity of pairs of galaxies are enhanced out to separations of 15Mpc/h. On scales smaller than 3Mpc/h the luminosities on galaxy pairs show a tight correlation. A comparison with the random-field model indicates that galaxy luminosities depend on the spatial distribution and galaxy-galaxy interactions. Early-type galaxies are also more strongly correlated, indicating morphological segregation. The galaxies in the PSCz catalog (Saunders et al. 2000) do not show significant luminosity segregation. This again illustrates that mainly early-type galaxies contribute to luminosity segregation. However, based on several independent investigations we show that the observed luminosity segregation can not be explained by the morphology-density relation alone.Comment: aastex, emulateapj5, 20 pages, 13 figures, several clarifying comments added, ApJ accepte

Cost-effectiveness of immediate total-body CT in patients with severe trauma (REACT-2 trial)

Background: The effect of immediate total-body CT (iTBCT) on health economic aspects in patients with severe trauma is an underreported issue. This study determined the cost-effectiveness of iTBCT compared with conventional radiological imaging with selective CT (standard work-up (STWU)) during the initial trauma evaluation. Methods: In this multicentre RCT, adult patients with a high suspicion of severe injury were randomized in-hospital to iTBCT or STWU. Hospital healthcare costs were determined for the first 6 months after the injury. The probability of iTBCT being cost-effective was calculated for various levels of willingness-to-pay per extra patient alive. Results: A total of 928 Dutch patients with complete clinical follow-up were included. Mean costs of hospital care were (sic)25 809 (95 per cent bias-corrected and accelerated (bca) c.i. (sic)22 617 to (sic)29 137) for the iTBCT group and (sic)26 155 ((sic)23 050 to (sic)29 344) for the STWU group, a difference per patient in favour of iTBCT of (sic)346 ((sic)4987 to (sic)4328) (P = 0.876). Proportions of patients alive at 6 months were not different. The proportion of patients alive without serious morbidity was 61.6 per cent in the iTBCT group versus 66.7 per cent in the STWU group (difference -5.1 per cent; P = 0.104). The probability of iTBCT being cost-effective in keeping patients alive remained below 0.56 for the whole group, but was higher in patients with multiple trauma (0.8-0.9) and in those with traumatic brain injury (more than 0.9). Conclusion: Economically, from a hospital healthcare provider perspective, iTBCT should be the diagnostic strategy of first choice in patients with multiple trauma or traumatic brain injury

Mark correlations: relating physical properties to spatial distributions

Mark correlations provide a systematic approach to look at objects both distributed in space and bearing intrinsic information, for instance on physical properties. The interplay of the objects' properties (marks) with the spatial clustering is of vivid interest for many applications; are, e.g., galaxies with high luminosities more strongly clustered than dim ones? Do neighbored pores in a sandstone have similar sizes? How does the shape of impact craters on a planet depend on the geological surface properties? In this article, we give an introduction into the appropriate mathematical framework to deal with such questions, i.e. the theory of marked point processes. After having clarified the notion of segregation effects, we define universal test quantities applicable to realizations of a marked point processes. We show their power using concrete data sets in analyzing the luminosity-dependence of the galaxy clustering, the alignment of dark matter halos in gravitational $N$-body simulations, the morphology- and diameter-dependence of the Martian crater distribution and the size correlations of pores in sandstone. In order to understand our data in more detail, we discuss the Boolean depletion model, the random field model and the Cox random field model. The first model describes depletion effects in the distribution of Martian craters and pores in sandstone, whereas the last one accounts at least qualitatively for the observed luminosity-dependence of the galaxy clustering.Comment: 35 pages, 12 figures. to be published in Lecture Notes of Physics, second Wuppertal conference "Spatial statistics and statistical physics

Novel biomarkers to detect occult cancer in patients with unprovoked venous thromboembolism: Rationale and design of the PLATO-VTE study

Occult cancer is detected in about 5% of patients with unprovoked venous thromboembolism (VTE) in the 12 months following VTE diagnosis. Current guidance suggests conducting a ‘limited’ cancer screening in these patients, consisting of medical history taking, physical examination, routine blood tests, chest X-ray, and age- and gender-specific testing, over full-body imaging. However, almost half of underlying cancers remain undetected with this approach. Blood-based liquid biopsies may provide an attractive addition or alternative to current cancer screening strategies, with a potentially higher detection rate while avoiding radiation or invasive testing. The PLATO-VTE study is an ongoing, investigator-initiated, multinational, prospective, observational cohort study comparing the sensitivity of novel biomarkers for detecting cancer with that of limited cancer screening in the setting of unprovoked VTE. Patients older than 40 years with a first episode of unprovoked VTE are eligible, while those with major and minor transient provoking risk factors for VTE are excluded. Patients undergo standard-of-care ‘limited’ cancer screening and are followed for 12 months for the occurrence of cancer. A blood sample for biomarker analysis is drawn within 10 days; a second sample is taken at 3 months to assess test result consistency over time. Three biomarkers are assessed: platelet mRNA, circulating tumor DNA, and plasma proteomics analysis. The sensitivity and predictive value of the biomarkers at baseline will be compared with those of limited screening. The results from the PLATO-VTE study may lead to reconsider current approaches for cancer screening in patients with unprovoked VTE

The capability set for work - correlates of sustainable employability in workers with multiple sclerosis

BACKGROUND: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes. METHODS: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'. RESULTS: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34). CONCLUSIONS: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014

Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial)

BACKGROUND: Most studies assessing praziquantel (PZQ) efficacy have used relatively insensitive diagnostic methods, thereby overestimating cure rate (CR) and intensity reduction rate (IRR). To determine accurately PZQ efficacy, we employed more sensitive DNA and circulating antigen detection methods. METHODOLOGY: A sub-analysis was performed based on a previously published trial conducted in children from Cote d'Ivoire with a confirmed Schistosoma mansoni infection, who were randomly assigned to a standard (single dose of PZQ) or intense treatment group (4 repeated doses of PZQ at 2-week intervals). CR and IRR were estimated based on PCR detecting DNA in a single stool sample and the up-converting particle lateral flow (UCP-LF) test detecting circulating anodic antigen (CAA) in a single urine sample, and compared with traditional Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA). PRINCIPAL FINDINGS: Individuals positive by all diagnostic methods (i.e., KK, POC-CCA, PCR, and UCP-LF CAA) at baseline were included in the statistical analysis (n = 125). PCR showed a CR of 45% (95% confidence interval (CI) 32-59%) in the standard and 78% (95% CI 66-87%) in the intense treatment group, which is lower compared to the KK results (64%, 95% CI 52-75%) and 88%, 95% CI 78-93%). UCP-LF CAA showed a significantly lower CR in both groups, 16% (95% CI 11-24%) and 18% (95% CI 12-26%), even lower than observed by POC-CCA (31%, 95% CI 17-35% and 36%, 95% CI 26-47%). A substantial reduction in DNA and CAA-levels was observed after the first treatment, with no further decrease after additional treatment and no significant difference in IRR between treatment groups. CONCLUSION/SIGNIFICANCE: The efficacy of (repeated) PZQ treatment was overestimated when using egg-based diagnostics. Quantitative worm-based diagnostics revealed that active Schistosoma infections are still present despite multiple treatments. These results stress the need for using accurate diagnostic tools to monitor different PZQ treatment strategies, in particular when moving toward elimination of schistosomiasis. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT02868385

Refining the criteria for immediate total-body CT after severe trauma

Objectives Initial trauma care could potentially be improved when conventional imaging and selective CT scanning is omitted and replaced by immediate total-body CT (iTBCT) scanning. Because of the potentially increased radiation exposure by this diagnostic approach, proper selection of the severely injured patients is mandatory. Methods In the REACT-2 trial, severe trauma patients were randomized to iTBCT or conventional imaging and selective CT based on predefined criteria regarding compromised vital parameters, clinical suspicion of severe injuries, or high-risk trauma mechanisms in five trauma centers. By logistic regression analysis with backward selection on the 15 study inclusion criteria, a revised set of criteria was derived and subsequently tested for prediction of severe injury and shifts in radiation exposure. Results In total, 1083 patients were enrolled with median ISS of 20 (IQR 9-29) and median GCS of 13 (IQR 3-15). Backward logistic regression resulted in a revised set consisting of nine original and one adjusted criteria. Positive predictive value improved from 76% (95% CI 74-79%) to 82% (95% CI 80-85%). Sensitivity decreased by 9% (95% CI 7-11%). The area under the receiver operating characteristics curve remained equal and was 0.80 (95% CI 0.77-0.83), original set 0.80 (95% CI 0.77-0.83). The revised set retains 8.78 mSv (95% CI 6.01-11.56) for 36% of the non-severely injured patients. Conclusions Selection criteria for iTBCT can be reduced from 15 to 10 clinically criteria. This improves the positive predictive value for severe injury and reduces radiation exposure for less severely injured patients

Resample-smoothing of Voronoi intensity estimators

Voronoi estimators are non-parametric and adaptive estimators of the intensity of a point process. The intensity estimate at a given location is equal to the reciprocal of the size of the Voronoi/Dirichlet cell containing that location. Their major drawback is that they tend to paradoxically under-smooth the data in regions where the point density of the observed point pattern is high, and over-smooth where the point density is low. To remedy this behaviour, we propose to apply an additional smoothing operation to the Voronoi estimator, based on resampling the point pattern by independent random thinning. Through a simulation study we show that our resample-smoothing technique improves the estimation substantially. In addition, we study statistical properties such as unbiasedness and variance, and propose a rule-of-thumb and a data-driven cross-validation approach to choose the amount of smoothing to apply. Finally we apply our proposed intensity estimation scheme to two datasets: locations of pine saplings (planar point pattern) and motor vehicle traffic accidents (linear network point pattern)

Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis

A more detailed understanding of the somatic genetic events that drive gastrointestinal adenocarcinomas is necessary to improve diagnosis and therapy. Using data from high-density genomic profiling arrays, we conducted an analysis of somatic copy-number aberrations in 486 gastrointestinal adenocarcinomas including 296 esophageal and gastric cancers. Focal amplifications were substantially more prevalent in gastric/esophageal adenocarcinomas than colorectal tumors. We identified 64 regions of significant recurrent amplification and deletion, some shared and others unique to the adenocarcinoma types examined. Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared with colorectal cancers. Amplified loci implicated genes with known involvement in carcinogenesis but also pointed to regions harboring potentially novel cancer genes, including a recurrent deletion found in 15% of esophageal tumors where the Runt transcription factor subunit RUNX1 was implicated, including by functional experiments in tissue culture. Together, our results defined genomic features that were common and distinct to various gut-derived adenocarcinomas, potentially informing novel opportunities for targeted therapeutic interventions