Quantitative CT analysis in patients with pulmonary emphysema: is lung function influenced by concomitant unspecific pulmonary fibrosis?

Purpose: Quantitative analysis of CT scans has proven to be a reproducible technique, which might help to understand the pathophysiology of chronic obstructive pulmonary disease (COPD) and combined pulmonary fibrosis and emphysema. The aim of this retrospective study was to find out if the lung function of patients with COPD with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III or IV and pulmonary emphysema is measurably influenced by high attenuation areas as a correlate of concomitant unspecific fibrotic changes of lung parenchyma. Patients and methods: Eighty-eight patients with COPD GOLD stage III or IV underwent CT and pulmonary function tests. Quantitative CT analysis was performed to determine low attenuation volume (LAV) and high attenuation volume (HAV), which are considered to be equivalents of fibrotic (HAV) and emphysematous (LAV) changes of lung parenchyma. Both parameters were determined for the whole lung, as well as peripheral and central lung areas only. Multivariate regression analysis was used to correlate HAV with different parameters of lung function. Results: Unlike LAV, HAV did not show significant correlation with parameters of lung function. Even in patients with a relatively high HAVof more than 10%, in contrast to HAV (p=0.786) only LAV showed a significantly negative correlation with forced expiratory volume in 1 second (r=−0.309, R2=0.096, p=0.003). A severe decrease of DLCO% was associated with both larger HAV (p=0.045) and larger LAV (p=0.001). Residual volume and FVC were not influenced by LAV or HAV. Conclusion: In patients with COPD GOLD stage III-IV, emphysematous changes of lung parenchyma seem to have such a strong influence on lung function, which is a possible effect of concomitant unspecific fibrosis is overwhelmed

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis : a phase I first-in-human study

Background: Nanoparticles hold considerable promise for aerosol-based intraperitoneal delivery in patients with carcinomatosis. Recently, results from preclinical and early clinical trials suggested that albumin-bound paclitaxel (ABP, Abraxane (TM)) may result in superior efficacy in the treatment of peritoneal metastases (PM) compared to the standard solvent-based paclitaxel formulation (Taxol (TM)). Here, we propose a phase I study of pressurized intraperitoneal aerosol chemotherapy (PIPAC) using ABP in patients with upper Gastrointestinal, breast, or ovarian cancer. Methods: Eligible patients with advanced, biopsy-proven PM from ovarian, breast, gastric, hepatobiliary, or pancreatic origin will undergo three PIPAC treatments using ABP with a 4-week interval. The dose of ABP will be escalated from 35 to 140 mg/m(2) using a Bayesian approach until the maximally tolerated dose is determined. The primary end point is dose-limiting toxicity. Secondary analyses include surgical morbidity, non-access rate, pharmacokinetic and pharmacodynamic analyses, quality of life, and exploratory circulating biomarker analyses. Discussion: ABP holds considerable promise for intraperitoneal aerosol delivery. The aim of this study is to determine the dose level for future randomized phase II trials using ABP in PIPAC therapy

Narrative discourse in young and older adults: behavioral and NIRS analyses

Discourse comprehension is at the core of communication capabilities, making it an important component of elderly populations' quality of life. The aim of this study is to evaluate changes in discourse comprehension and the underlying brain activity. Thirty-six participants read short stories and answered related probes in three conditions: micropropositions, macropropositions and situation models. Using near-infrared spectroscopy (NIRS), the variation in oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) concentrations was assessed throughout the task. The results revealed that the older adults performed with equivalent accuracy to the young ones at the macroproposition level of discourse comprehension, but were less accurate at the microproposition and situation model levels. Similar to what is described in the compensation-related utilization of neural circuits hypothesis (CRUNCH) model, older participants tended to have greater activation in the left dorsolateral prefrontal cortex while reading in all conditions. Although it did not enable them to perform similarly to younger participants in all conditions, this over-activation could be interpreted as a compensation mechanism

Nab-PIPAC: a phase IB study protocol of intraperitoneal cisplatin and nab-paclitaxel administered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in the treatment of advanced malignancies confined to the peritoneal cavity

Introduction: Intraperitoneal dissemination is a major problem resulting in very poor prognosis and a rapid marked deterioration in the quality of life of patients. Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is an emergent laparoscopic procedure aiming to maximise local efficacy and to reduce systemic side effects. Methods and analysis: Nab-PIPAC, a bicentre open-label phase IB, aims to evaluate safety of nab-paclitaxel and cisplatin association using in patients with peritoneal carcinomatosis (PC) of gastric, pancreatic or ovarian origin as ≥1 prior line of systemic therapy. Using a 3+3 design, sequential intraperitoneal laparoscopic application of nab-paclitaxel (7.5, 15, 25, 37.5, 52.5 and 70 mg/m2) and cisplatin (10.5 mg/m2) through a nebuliser to a high-pressure injector at ambient temperature with a maximal upstream pressure of 300 psi. Treatment maintained for 30 min at a pressure of 12 mm Hg and repeated4-6 weeks intervals for three courses total.A total of 6-36 patients are expected, accrual is ongoing. Results are expected in 2024.The primary objective of Nab-PIPAC trial is to assess tolerability and safety of nab-paclitaxel and cisplatin combination administered intraperitoneally by PIPAC in patients with PC of gastric, pancreatic or ovarian origin. This study will determine maximum tolerated dose and provide pharmacokinetic data. Ethic and dissemination: Ethical approval was obtained from the ethical committees of Geneva and Vaud (CCER-2018-01327). The study findings will be published in an open-access, peer-reviewed journal and presented at relevant conferences and research meetings. Trial registration number: NCT04000906.</p

Regulation of insulin-like growth factor binding protein synthesis and secretion in human retinal pigment epithelial cells

Cultured human retinal pigment epithelial cells (RPE) secrete insulin-like growth factor binding proteins (IGFBPs), a family of polypeptides which modulate the actions of the insulin-like growth factors. RPE cells secrete two IGFBPs with Mr estimates of 34,000 and 46,000, respectively. Treatment of RPE cells with IGF-I markedly stimulated the secretion of the 46,000 Mr form. This stimulation occurred via an IGF-I receptor independent mechanism because both [QAYL]IGF-I (an IGF-I analogue with decreased affinity for the IGFBPs but normal affinity for the IGF-I receptor) and Α-IR 3 (a blocking monoclonal antibody against the IGF-I receptor) had no effect on IGF-I stimulated increases in IGFBPs. Additionally, [QAYL]IGF-I enhanced RPE cell proliferation to the same magnitude as IGF-I. Treatment with IGF-I, [QAYL]IGF-I, or Α-IR 3 had no effect on steady-state levels of the 2.5 kb IGFBP-3 or the 1.3 kb IGFBP-6 mRNA transcripts as measured by Northern blotting and quantitative autoradiography. Forskolin and a group of candidate growth factors, including platelet-derived growth factor, epidermal growth factor, and acidic and basic fibroblast growth factor, modestly increased IGFBP secretion when compared to untreated cells, but these effects were small when compared to IGF-I treatment. Fetal calf serum enhanced the presence of the 2.5 kb IGFBP-3 mRNA transcript in a dose-dependent fashion but had no effect on the 1.3 kb IGFBP-6 mRNA transcript. IGF-I, forskolin, and the candidate growth factors had no effect on either IGFBP-3 or IGFBP-6 mRNA. These data suggest that the production of IGFBPs in human RPE cells is regulated by distinct mechanisms which include (1) an IGF-I receptor independent interaction of IGF-I with secreted IGFBPs and (2) de novo synthesis of IGFBPs by serum-containing factors. © 1994 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49887/1/1041580124_ftp.pd

Frictional drag between quantum wells mediated by phonon exchange

We use the Kubo formalism to evaluate the contribution of acoustic phonon exchange to the frictional drag between nearby two-dimensional electron systems. In the case of free phonons, we find a divergent drag rate ($\tau_{D}^{-1}$). However, $\tau_{D}^{-1}$ becomes finite when phonon scattering from either lattice imperfections or electronic excitations is accounted for. In the case of GaAs quantum wells, we find that for a phonon mean free path $\ell_{ph}$ smaller than a critical value, imperfection scattering dominates and the drag rate varies as $ln (\ell_{ph}/d)$ over many orders of magnitude of the layer separation $d$. When $\ell_{ph}$ exceeds the critical value, the drag rate is dominated by coupling through an electron-phonon collective mode localized in the vicinity of the electron layers. We argue that the coupled electron-phonon mode may be observable for realistic parameters. Our theory is in good agreement with experimental results for the temperature, density, and $d$-dependence of the drag rate.Comment: 45 pages, LaTeX, 8 postscript file figure

histoneHMM:Differential analysis of histone modifications with broad genomic footprints

BACKGROUND: ChIP-seq has become a routine method for interrogating the genome-wide distribution of various histone modifications. An important experimental goal is to compare the ChIP-seq profiles between an experimental sample and a reference sample, and to identify regions that show differential enrichment. However, comparative analysis of samples remains challenging for histone modifications with broad domains, such as heterochromatin-associated H3K27me3, as most ChIP-seq algorithms are designed to detect well defined peak-like features. RESULTS: To address this limitation we introduce histoneHMM, a powerful bivariate Hidden Markov Model for the differential analysis of histone modifications with broad genomic footprints. histoneHMM aggregates short-reads over larger regions and takes the resulting bivariate read counts as inputs for an unsupervised classification procedure, requiring no further tuning parameters. histoneHMM outputs probabilistic classifications of genomic regions as being either modified in both samples, unmodified in both samples or differentially modified between samples. We extensively tested histoneHMM in the context of two broad repressive marks, H3K27me3 and H3K9me3, and evaluated region calls with follow up qPCR as well as RNA-seq data. Our results show that histoneHMM outperforms competing methods in detecting functionally relevant differentially modified regions. CONCLUSION: histoneHMM is a fast algorithm written in C++ and compiled as an R package. It runs in the popular R computing environment and thus seamlessly integrates with the extensive bioinformatic tool sets available through Bioconductor. This makeshistoneHMM an attractive choice for the differential analysis of ChIP-seq data. Software is available from http://histonehmm.molgen.mpg.de

Fusion of heterogenous sensor data in border surveillance

Wide area surveillance has become of critical importance particularly for border control between countries where vast forested land border areas are to be monitored. In this paper we address the problem of the automatic detection of activity in forbidden areas, namely forested land border areas. In order to avoid false detections, often triggered in dense vegetation with single sensors such as radar, in this paper we present a multi sensor fusion and tracking system using passive infrared detectors in combination with automatic person detection from thermal and visual video camera images. The approach combines weighted maps with a rule engine that associates data from multiple weighted maps. The proposed approach is tested on real data collected by the EU FOLDOUT project in a location representative of a range of forested EU borders. The results show that the proposed approach can eliminate single-sensor false detections and enhance accuracy by up to 50%