PYRO-NN: Python Reconstruction Operators in Neural Networks

Purpose: Recently, several attempts were conducted to transfer deep learning to medical image reconstruction. An increasingly number of publications follow the concept of embedding the CT reconstruction as a known operator into a neural network. However, most of the approaches presented lack an efficient CT reconstruction framework fully integrated into deep learning environments. As a result, many approaches are forced to use workarounds for mathematically unambiguously solvable problems. Methods: PYRO-NN is a generalized framework to embed known operators into the prevalent deep learning framework Tensorflow. The current status includes state-of-the-art parallel-, fan- and cone-beam projectors and back-projectors accelerated with CUDA provided as Tensorflow layers. On top, the framework provides a high level Python API to conduct FBP and iterative reconstruction experiments with data from real CT systems. Results: The framework provides all necessary algorithms and tools to design end-to-end neural network pipelines with integrated CT reconstruction algorithms. The high level Python API allows a simple use of the layers as known from Tensorflow. To demonstrate the capabilities of the layers, the framework comes with three baseline experiments showing a cone-beam short scan FDK reconstruction, a CT reconstruction filter learning setup, and a TV regularized iterative reconstruction. All algorithms and tools are referenced to a scientific publication and are compared to existing non deep learning reconstruction frameworks. The framework is available as open-source software at \url{https://github.com/csyben/PYRO-NN}. Conclusions: PYRO-NN comes with the prevalent deep learning framework Tensorflow and allows to setup end-to-end trainable neural networks in the medical image reconstruction context. We believe that the framework will be a step towards reproducible researchComment: V1: Submitted to Medical Physics, 11 pages, 7 figure

Techno-economic heat transfer optimization of large scale latent heat energy storage systems in solar thermal power plants

Concentrated solar power plants with integrated storage systems are key technologies for sustainable energy supply systems and reduced anthropogenic CO2-emissions. Developing technologies include direct steam generation in parabolic trough systems, which offer benefits due to higher steam temperatures and, thus, higher electrical efficiencies. However, no large scale energy storage technology is available yet. A promising option is a combined system consisting of a state-of-the art sensible molten salt storage system and a high temperature latent heat thermal energy storage system (LHTESS). This paper discusses the systematic development and optimization of heat transfer structures in LHTESS from a technological and economic point of view. Two evaluation parameters are developed in order to minimize the specific investment costs. First, the specific product costs determine the optimum equipment of the latent heat storage module, i.e. the finned tube. The second parameter reflects the interacting behavior of the LHTESS and the steam turbine during discharge. This behavior is described with a simplified power block model that couples both components

High-Temperature Heat Pump for Wellness Applications Using CO2 as a Refrigerant

Building technology recently has been affected by great innovations to reduce energy demand and to enable self-sufficient operation. To test innovations and prove practicality, EMPA has built a research building called NEST, where different demonstration projects from the building industry can be integrated and scientifically monitored. Furthermore, the sector of wellness applications shows significant potential for improving energy efficiency. Usually, spa facilities such as saunas and steam baths are based on direct electric or fossil heating which is extremely energy intensive and results in high operating costs. In order to establish a more energy efficient technology to provide heat to wellness areas, the present work proposes the usage of a high temperature heat pump with CO2 as a refrigerant. Carbon dioxide is currently favored by many heat pump applications due to the demand for low-GWP refrigerants with non-toxic and non-flammable properties. High-temperature heat pumps with CO2 as a refrigerant are already available on the market and reach supply temperatures typically up to 100 °C. Wellness applications require temperatures up to 130 °C on the supplier side, which requires new system design. On the consumption side, the heat will be used on a wide variety of temperature levels considering different saunas, showers and space heating. In this context, a stratified storage system ensures the heat output on the desired temperature level. Therefore, the heat exchanger unit as well as the operating range of the heat pump are the major challenges. In Coorporation with Scheco AG, a new CO2 refrigerant system has been designed and set up as a part of EMPA research building by means of a pilot installation including different saunas, steam bath and showers. Measurements will be performed as soon as possible to start the optimization process of the system

Complementary Keratoconus Indices Based on Topographical Interpretation of Biomechanical Waveform Parameters: A Supplement to Established Keratoconus Indices

Purpose:To build new models with the Ocular Response Analyzer (ORA) waveform parameters to create new indices analogous to established topographic keratoconus indices.Method:Biomechanical, tomographic, and topographic measurements of 505 eyes from the Homburger Keratoconus Centre were included. Thirty seven waveform parameters (WF) were derived from the biomechanical measurement with the ORA. Area under curve (ROC, receiver operating characteristic) was used to quantify the screening performance. A logistic regression analysis was used to create two new keratoconus prediction models based on these waveform parameters to resample the clinically established keratoconus indices from Pentacam and TMS-5.Results:ROC curves show the best results for the waveform parameters P1area, P2area, h1, h2, dive1, mslew1, aspect1, aplhf, dslope1. The new keratoconus prediction model to resample the Pentacam topographic keratoconus index (TKC) was: WFTKC = –4.068 + 0.002×P2area – 0.005×dive1 – 0.01×h1 – 2.501×aplhf, which achieves a sensitivity of 90.3% and specificity of 89.4%; to resample the TMS-5 keratoconus classification index (KCI) it was: WFKCI = –3.606 + 0.002×P2area which achieves a sensitivity of 75.4% and a specificity of 81.8%.Conclusion:Additional to the biomechanically provided Keratoconus Index two new indices which were based on the topographic gold standards (either Pentacam or TMS-5) were created. Of course, these do not replace the original topographic measurement

Randomized, Double-Blind Comparative Trial of Subunit and Virosomal Influenza Vaccines for Immunocompromised Patients

Background.. To our knowledge, no study to date has compared the effects of a subunit influenza vaccine with those of a virosomal influenza vaccine on immunocompromised patients. Methods.. A prospective, double-blind, randomized study was conducted to compare the immunogenicity and reactogenicity of subunit and virosomal influenza vaccines for adult patients who had an immunosuppressive disease or who were immunocompromised as a result of treatment. Results.. There were 304 patients enrolled in our study: 131 with human immunodeficiency virus (HIV) infection, 47 with a chronic rheumatologic disease, 74 who underwent a renal transplant, 47 who received long-term hemodialysis, and 5 who had some other nephrologic disease. There were 151 patients who received the subunit vaccine and 153 patients who received the virosomal vaccine. A slightly higher percentage of patients from the subunit vaccine group were protected against all 3 influenza vaccine strains after being vaccinated, compared with patients from the virosomal vaccine group (41% vs. 30% of patients; P=.03). Among HIV-infected patients, the level of HIV RNA, but not the CD4 cell count, was an independent predictor of vaccine response. Among renal transplant patients, treatment with mycophenolate significantly reduced the immune response to vaccination. The 2 vaccines were comparable with regard to the frequency and severity of local and systemic reactions within 7 days after vaccination. Disease-specific scores for the activity of rheumatologic diseases did not indicate flare-ups 4-6 weeks after vaccination. Conclusions.. For immunosuppressed patients, the subunit vaccine was slightly more immunogenic than the virosomal vaccine. The 2 vaccines were comparable with regard to reactogenicity. Vaccine response decreased with increasing degree of immune suppression. Among HIV-infected patients, the viral load, rather than the CD4 cell count, predicted the protective immune response to the vaccine. Clinical trials registration.. NCT0078338

A multicenter real-world evidence study in the Swiss treatment landscape of chronic myeloid leukemia

Background: The real-world experience of Swiss chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) is largely unknown, in particular with regard to achievement of response per European Leukemia Net (ELN) criteria and adherence to ELN recommendations. Methods: This was a retrospective, non-interventional, multicenter chart review of patients with newly diagnosed CML who had received first-line TKI and were solely treated with TKIs between 2010 and 2015, with a minimum follow-up of 18 months, at six Swiss hospitals. Effectiveness was evaluated according to ELN 2013 milestone achievements at 3, 6, 12 and 18 months, and at last follow-up. Results: Data from 63 patients (56% men; median age at diagnosis 55 years) were collected (first-line imatinib [n = 27], nilotinib [n = 27], dasatinib [n = 8], or ponatinib [n = 1]). TKI switches (49 times) and dosing changes (165 times) due to intolerance or insufficient response were frequent. Compared with patients receiving first-line imatinib, a higher proportion of patients receiving first-line nilotinib or dasatinib achieved optimal response at all timepoints, irrespective of subsequent TKI therapy, and a higher proportion of patients treated with first-line nilotinib and dasatinib reached deep molecular response (BCR-ABL1IS ≤ 0.01%) at 18 months (42 and 38%, respectively, versus 27%). Patients who received nilotinib or dasatinib switched therapies less frequently than patients treated with imatinib, irrespective of subsequent TKI therapy. Conclusions: Although patient numbers were small, this real-world evidence study with patients with CML confirms that ELN guidelines are generally implemented in Swiss clinical practice, with a large proportion of patients achieving ELN 2013 milestones. While TKI use involved all inhibitors approved at the time of the study, an unexpectedly high number of TKI therapy switches suggests a clear difference in TKI use between registration trials and clinical practice. Keywords: Chronic myeloid leukemia; Deep molecular response; Real-world evidence; Tyrosine kinase inhibitors

Extrastriatal changes in patients with late-onset glutaric aciduria type I highlight the risk of long-term neurotoxicity

Background: Without neonatal initiation of treatment, 80–90% of patients with glutaric aciduria type 1 (GA1) develop striatal injury during the first six years of life resulting in a complex, predominantly dystonic movement disorder. Onset of motor symptoms may be acute following encephalopathic crisis or insidious without apparent crisis. Additionally, so-called late-onset GA1 has been described in single patients diagnosed after the age of 6 years. With the aim of better characterizing and understanding late-onset GA1 we analyzed clinical findings, biochemical phenotype, and MRI changes of eight late-onset patients and compared these to eight control patients over the age of 6 years with early diagnosis and start of treatment. Results: No late-onset or control patient had either dystonia or striatal lesions on MRI. All late-onset (8/8) patients were high excretors, but only four of eight control patients. Two of eight late-onset patients were diagnosed after the age of 60 years, presenting with dementia, tremor, and epilepsy, while six were diagnosed before the age of 30 years: Three were asymptomatic mothers identified by following a positive screening result in their newborns and three had non-specific general symptoms, one with additional mild neurological deficits. Frontotemporal hypoplasia and white matter changes were present in all eight and subependymal lesions in six late-onset patients. At comparable age a greater proportion of late-onset patients had (non-specific) clinical symptoms and possibly subependymal nodules compared to control patients, in particular in comparison to the four clinically and MR-wise asymptomatic low-excreting control patients. Conclusions: While clinical findings are non-specific, frontotemporal hypoplasia and subependymal nodules are characteristic MRI findings of late-onset GA1 and should trigger diagnostic investigation for this rare disease. Apart from their apparent non-susceptibility for striatal injury despite lack of treatment, patients with late-onset GA1 are not categorically different from early treated control patients. Differences between late-onset patients and early treated control patients most likely reflect greater cumulative neurotoxicity in individuals remaining undiagnosed and untreated for years, even decades as well as the higher long-term risk of high excretors for intracerebral accumulation of neurotoxic metabolites compared to low excretors

Magnetic-activated cell sorting (MACS) can be used as a large-scale method for establishing zebrafish neuronal cell cultures

Neuronal cell cultures offer a crucial tool to mechanistically analyse regeneration in the nervous system. Despite the increasing importance of zebrafish (Danio rerio) as an in vivo model in neurobiological and biomedical research, in vitro approaches to the nervous system are lagging far behind and no method is currently available for establishing enriched neuronal cell cultures. Here we show that magnetic-activated cell sorting (MACS) can be used for the large-scale generation of neuronal-restricted progenitor (NRP) cultures from embryonic zebrafish. Our findings provide a simple and semi-automated method that is likely to boost the use of neuronal cell cultures as a tool for the mechanistic dissection of key processes in neuronal regeneration and development

Wound Healing in Mice with High-Fat Diet- or ob Gene-Induced Diabetes-Obesity Syndromes: A Comparative Study

In the past, the genetically diabetic-obese diabetes/diabetes (db/db) and obese/obese (ob/ob) mouse strains were used to investigate mechanisms of diabetes-impaired wound healing. Here we determined patterns of skin repair in genetically normal C57Bl/6J mice that were fed using a high fat diet (HFD) to induce a diabetes-obesity syndrome. Wound closure was markedly delayed in HFD-fed mice compared to mice which had received a standard chow diet (CD). Impaired wound tissue of HFD mice showed a marked prolongation of wound inflammation. Expression of vascular endothelial growth factor (VEGF) was delayed and associated with the disturbed formation of wound margin epithelia and an impaired angiogenesis in the reduced granulation tissue. Normal wound contraction was retarded and disordered. Wound disorders in obese C57Bl/6J mice were paralleled by a prominent degradation of the inhibitor of NFκB (IκB-α) in the absence of an Akt activation. By contrast to impaired wound conditions in ob/ob mice, late wounds of HFD mice did not develop a chronic inflammatory state and were epithelialized after 11 days of repair. Thus, only genetically obese and diabetic ob/ob mice finally developed chronic wounds and therefore represent a better suited experimental model to investigate diabetes-induced wound healing disorders