A new synthetic route, to prepare an alkylated indacenodithieno3,2‐bthiophene‐based nonfullerene acceptor (C8‐ITIC), is reported. Compared to the reported ITIC with phenylalkyl side chains, the new ...acceptor C8‐ITIC exhibits a reduction in the optical band gap, higher absorptivity, and an increased propensity to crystallize. Accordingly, blends with the donor polymer PBDB‐T exhibit a power conversion efficiency (PCE) up to 12.4%. Further improvements in efficiency are found upon backbone fluorination of the donor polymer to afford the novel material PFBDB‐T. The resulting blend with C8‐ITIC shows an impressive PCE up to 13.2% as a result of the higher open‐circuit voltage. Electroluminescence studies demonstrate that backbone fluorination reduces the energy loss of the blends, with PFBDB‐T/C8‐ITIC‐based cells exhibiting a small energy loss of 0.6 eV combined with a high JSC of 19.6 mA cm−2.
The synthesis of a novel alkylated indacenodithioeno3,2‐bthiophene (C8‐IDTT) based nonfullerene acceptor (C8‐ITIC), is reported. Compared to ITIC with phenylalkyl side chains, the acceptor exhibits a redshifted absorption with increased absorptivity. Solar cell power conversion efficiencies (PCEs) of up to 13.2 % are achieved, with the high PCE attributed to the broad absorption, high crystallinity of C8‐ITIC and low voltage loss.
The metabolic responses of bacteria to dynamic extracellular conditions drives not only the behavior of single species, but also entire communities of microbes. Over the last decade, genome-scale ...metabolic network reconstructions have assisted in our appreciation of important metabolic determinants of bacterial physiology. These network models have been a powerful force in understanding the metabolic capacity that species may utilize in order to succeed in an environment. Increasingly, an understanding of context-specific metabolism is critical for elucidating metabolic drivers of larger phenotypes and disease. However, previous approaches to use network models in concert with omics data to better characterize experimental systems have met challenges due to assumptions necessary by the various integration platforms or due to large input data requirements. With these challenges in mind, we developed RIPTiDe (Reaction Inclusion by Parsimony and Transcript Distribution) which uses both transcriptomic abundances and parsimony of overall flux to identify the most cost-effective usage of metabolism that also best reflects the cell's investments into transcription. Additionally, in biological samples where it is difficult to quantify specific growth conditions, it becomes critical to develop methods that require lower amounts of user intervention in order to generate accurate metabolic predictions. Utilizing a metabolic network reconstruction for the model organism Escherichia coli str. K-12 substr. MG1655 (iJO1366), we found that RIPTiDe correctly identifies context-specific metabolic pathway activity without supervision or knowledge of specific media conditions. We also assessed the application of RIPTiDe to in vivo metatranscriptomic data where E. coli was present at high abundances, and found that our approach also effectively predicts metabolic behaviors of host-associated bacteria. In the setting of human health, understanding metabolic changes within bacteria in environments where growth substrate availability is difficult to quantify can have large downstream impacts on our ability to elucidate molecular drivers of disease-associated dysbiosis across the microbiota. Our results indicate that RIPTiDe may have potential to provide understanding of context-specific metabolism of bacteria within complex communities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or ...special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
Genome-scale metabolic network reconstructions (GENREs) are valuable tools for understanding microbial metabolism. The process of automatically generating GENREs includes identifying metabolic ...reactions supported by sufficient genomic evidence to generate a draft metabolic network. The draft GENRE is then gapfilled with additional reactions in order to recapitulate specific growth phenotypes as indicated with associated experimental data. Previous methods have implemented absolute mapping thresholds for the reactions automatically included in draft GENREs; however, there is growing evidence that integrating annotation evidence in a continuous form can improve model accuracy. There is a need for flexibility in the structure of GENREs to better account for uncertainty in biological data, unknown regulatory mechanisms, and context-specificity associated with data inputs. To address this issue, we present a novel method that provides a framework for quantifying combined genomic, biochemical, and phenotypic evidence for each biochemical reaction during automated GENRE construction. Our method, Constraint-based Analysis Yielding reaction Usage across metabolic Networks (CANYUNs), generates accurate GENREs with a quantitative metric for the cumulative evidence for each reaction included in the network. The structuring of CANYUNs allows for the simultaneous integration of three data inputs while maintaining all supporting evidence for biochemical reactions that may be active in an organism. CANYUNs is designed to maximize the utility of experimental and annotation datasets and to ultimately assist in the curation of the reference datasets used for the automatic construction of metabolic networks. We validated CANYUNs by generating an E. coli K-12 model and compared it to the manually curated reconstruction iML1515. Finally, we demonstrated the use of CANYUNs to build a model by generating an E. coli Nissle CANYUNs model using novel phenotypic data that we collected. This method may address key challenges for the procedural construction of metabolic networks by leveraging uncertainty and redundancy in biological data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a novel methodology to construct a Boolean dynamic model from time series metagenomic information and integrate this modeling with genome-scale metabolic network reconstructions to ...identify metabolic underpinnings for microbial interactions. We apply this in the context of a critical health issue: clindamycin antibiotic treatment and opportunistic Clostridium difficile infection. Our model recapitulates known dynamics of clindamycin antibiotic treatment and C. difficile infection and predicts therapeutic probiotic interventions to suppress C. difficile infection. Genome-scale metabolic network reconstructions reveal metabolic differences between community members and are used to explore the role of metabolism in the observed microbial interactions. In vitro experimental data validate a key result of our computational model, that B. intestinihominis can in fact slow C. difficile growth.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Limited data exist about the international burden of severe sepsis in critically ill children.
To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive ...care units to better inform interventional trials.
A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality.
Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range IQR, 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR, 12-28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,471 corrected patients per group.
Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.
We analyzed transcriptomes (n = 211), whole exomes (n = 99) and targeted exomes (n = 103) from 216 malignant pleural mesothelioma (MPM) tumors. Using RNA-seq data, we identified four distinct ...molecular subtypes: sarcomatoid, epithelioid, biphasic-epithelioid (biphasic-E) and biphasic-sarcomatoid (biphasic-S). Through exome analysis, we found BAP1, NF2, TP53, SETD2, DDX3X, ULK2, RYR2, CFAP45, SETDB1 and DDX51 to be significantly mutated (q-score ≥ 0.8) in MPMs. We identified recurrent mutations in several genes, including SF3B1 (∼2%; 4/216) and TRAF7 (∼2%; 5/216). SF3B1-mutant samples showed a splicing profile distinct from that of wild-type tumors. TRAF7 alterations occurred primarily in the WD40 domain and were, except in one case, mutually exclusive with NF2 alterations. We found recurrent gene fusions and splice alterations to be frequent mechanisms for inactivation of NF2, BAP1 and SETD2. Through integrated analyses, we identified alterations in Hippo, mTOR, histone methylation, RNA helicase and p53 signaling pathways in MPMs.
Organic photovoltaics are an emerging solar power technology which embody properties such as transparency, flexibility, and rapid, roll to roll manufacture, opening the potential for unique niche ...applications. We report a detailed techno-economic analysis of one such application, namely the photovoltaic greenhouse, and discuss whether the unique properties of the technology can provide advantages over conventional photovoltaics. The potential for spectral selectivity through the choice of OPV materials is evaluated for the case of a photovoltaic greenhouse. The action spectrum of typical greenhouse crops is used to determine the impact on crop growth of blocking different spectral ranges from the crops. Transfer matrix optical modelling is used to assess the efficiency and spectrally resolved transparency of a variety of commercially available semi-conducting polymer materials, in addition to a non-commercial low-band-gap material with absorption outside that required for crop growth. Economic analysis suggests there could be a huge potential for OPV greenhouses if aggressive cost targets can be met. Technical analysis shows that semi-transparent OPV devices may struggle to perform better than opaque crystalline silicon with partial coverage, however, OPV devices using the low-band-gap material PMDPP3T, as well as a high efficiency mid-band-gap polymer PCDTBT, can demonstrate improved performance in comparison to opaque, flexible thin-film modules such as CIGS. These results stress the importance of developing new, highly transparent electrode and interlayer materials, along with high efficiency active layers, if the full potential of this application is going to be realised.
We aimed to update a previously published, multi-institutional nomogram of outcomes for salvage radiotherapy (SRT) following radical prostatectomy (RP) for prostate cancer, including patients treated ...in the contemporary era.
Individual data from node-negative patients with a detectable post-RP prostate-specific antigen (PSA) treated with SRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 10 academic institutions. Freedom from biochemical failure (FFBF) and distant metastases (DM) rates were estimated, and predictive nomograms were generated.
Overall, 2,460 patients with a median follow-up of 5 years were included; 599 patients (24%) had a Gleason score (GS) ≤ 6, 1,387 (56%) had a GS of 7, 244 (10%) had a GS of 8, and 230 (9%) had a GS of 9 to 10. There were 1,370 patients (56%) with extraprostatic extension (EPE), 452 (18%) with seminal vesicle invasion (SVI), 1,434 (58%) with positive surgical margins, and 390 (16%) who received ADT (median, 6 months). The median pre-SRT PSA was 0.5 ng/mL (interquartile range, 0.3 to 1.1). The 5-yr FFBF rate was 56% overall, 71% for those with a pre-SRT PSA level of 0.01 to 0.2 ng/mL (n = 441), 63% for those with a PSA of 0.21 to 0.50 ng/mL (n = 822), 54% for those with a PSA of 0.51 to 1.0 ng/mL (n = 533), 43% for those with a PSA of 1.01 to 2.0 ng/mL (n = 341), and 37% for those with a PSA > 2.0 ng/mL (n = 323); P < .001. On multivariable analysis, pre-SRT PSA, GS, EPE, SVI, surgical margins, ADT use, and SRT dose were associated with FFBF. Pre-SRT PSA, GS, SVI, surgical margins, and ADT use were associated with DM, whereas EPE and SRT dose were not. The nomogram concordance indices were 0.68 (FFBF) and 0.74 (DM).
Early SRT at low PSA levels after RP is associated with improved FFBF and DM rates. Contemporary nomograms can estimate individual patient outcomes after SRT in the modern era.
Management of bladder cancer (BC) is primarily driven by stage, grade, and biological potential. Knowledge of each is derived using clinical, histopathological, and radiological investigations. This ...multimodal approach reduces the risk of error from one particular test, but may present a staging dilemma when results conflict. Multiparametric magnetic resonance imaging (mpMRI) may improve patient care through imaging of the bladder with better resolution of the tissue planes than computed tomography and without radiation exposure.
To define a standardized approach to imaging and reporting mpMRI for BC, by developing a VI-RADS score.
We created VI-RADS (Vesical Imaging-Reporting And Data System) through consensus using existing literature.
We describe standard imaging protocols and reporting criteria (including size, location, multiplicity, and morphology) for bladder mpMRI. We propose a five-point VI-RADS score, derived using T2-weighted MRI, diffusion-weighted imaging, and dynamic contrast enhancement, which suggests the risks of muscle invasion. We include sample images used to understand VI-RADS.
We hope that VI-RADS will standardize reporting, facilitate comparisons between patients, and in future years, will be tested and refined if necessary. While we do not advocate mpMRI for all patients with BC, this imaging may compliment pathology or reduce radiation-based imaging. Bladder mpMRI may be most useful in patients with non–muscle-invasive cancers, in expediting radical treatment or for determining response to bladder-sparing approaches.
Magnetic resonance imaging (MRI) scans for bladder cancer are becoming more common and may provide accurate information that helps improve patient care. Here, we describe a standardized reporting criterion for bladder MRI. This should improve communication between doctors and allow better comparisons between patients.
Magnetic resonance imaging (MRI) scans for bladder cancer are becoming more common and may provide accurate information that helps improve patient care. Here, we describe a standardized reporting criterion for bladder MRI. This should improve communication between doctors and allow better comparisons between patients.
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