Bioavailability of Manufactured Nanomaterials in Terrestrial Ecosystems

Manufactured nanomaterials (MNMs) from the rapidly increasing number of consumer products that contain MNMs are being discharged into waste streams. Increasing evidence suggests that several classes of MNMs may accumulate in sludge derived from wastewater treatment and ultimately in soil following land application as biosolids. Little research has been conducted to evaluate the impact of MNMs on terrestrial ecosystems, despite the fact that land application of biosolids from wastewater treatment will be a major pathway for the introduction of MNMs to the environment. To begin addressing this knowledge gap, we have conducted a series of experiments designed to test how bioavailable MNMs are to terrestrial ecoreceptors when exposed through a variety of pathways. First, we used the model organisms Nicotiana tabacum L. cv Xanthi (tobacco) and Triticum aestivum (wheat) to investigate plant uptake of 10, 30 and 50 nm diameter gold (Au) MNMs coated with either tannate (T-MNMs) or citrate (C-MNMs). Both C-MNMs and T-MNMs of each size treatment bioaccumulated in tobacco, but no bioaccumulation of MNMs was observed for any treatment in wheat. In a second exposure, we investigated the potential for bioaccumulation of MNMs from contaminated plant surfaces by a terrestrial secondary consumer, tobacco hornworm (Manduca sexta). We found that hornworms bioaccumulate Au MNMs, but that the assimilation efficiency of bioaccumulation was low. Hornworms eliminate ingested Au MNMs rapidly from 0-24 h, but very slowly from 1 d to 7 d. Finally, we used the model organisms tobacco and tobacco hornworm to investigate the potential for trophic transfer of Au MNMs. Biomagnification of Au MNMs was observed in the hornworms. We have demonstrated that MNMs of a wide range of size and with different surface chemistries are bioavailable to plants, that MNMs resuspended by wind, rain, biota, and mechanical disturbance from soil onto plant surfaces are bioavailable to terrestrial consumers, and that trophic transfer and biomagnification of plant accumulated MNMs can occur. These results have important implications for risks associated with nanotechnology, including the potential for human exposure

Nanoparticles Composed of Zn and ZnO Inhibit \u3cem\u3ePeronospora tabacina\u3c/em\u3e Spore Germination \u3cem\u3ein vitro\u3c/em\u3e and \u3cem\u3eP. tabacina\u3c/em\u3e Infectivity on Tobacco Leaves

Manufactured nanoparticles (NPs) are increasingly being used for commercial purposes and certain NP types have been shown to have broad spectrum antibacterial activity. In contrast, their activities against fungi and fungi-like oomycetes are less studied. Here, we examined the potential of two types of commercially available Zn NPs (Zn NPs and ZnO NPs) to inhibit spore germination and infectivity on tobacco leaves resulting from exposure to the fungi-like oomycete pathogen Peronospora tabacina (P. tabacina). Both types of NPs, as well as ZnCl2 and bulk ZnO control treatments, inhibited spore germination compared to a blank control. ZnO ENMs were shown to be a much more powerful suppressor of spore germination and infectivity than bulk ZnO. ZnO and Zn NPs significantly inhibited leaf infection at 8 and 10 mg·L−1, respectively. Both types of NPs were found to provide substantially higher concentration dependent inhibition of spore germination and infectivity than could be readily explained by the presence of dissolved Zn. These results suggest that both NP types have potential for use as economic, low-dose, potentially non-persistent anti-microbial agents against the oomycete P. tabacina

Survival outcome according to KRAS mutation status in newly diagnosed patients with stage IV non-small cell lung cancer treated with platinum doublet chemotherapy

INTRODUCTION: Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20-25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear. METHODS: We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58-2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48-1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01). CONCLUSIONS: KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy

kNN Classification of Epilepsy Brainwaves

Epilepsy is a disorder of the normal brain function by the existence of abnormal synchronous discharges in large groups of neurons in brain structures and it is estimated about 1% of the world’s population suffers from this disease [Tzallas et al., 2009]. It has been reported that the brainwave of Epilepsy patient mostly in sharp, spike and complex wave pattern [Tzallas et al., 2009]. In addition, Epilepsy brainwaves pattern lies in wide variety of Electroencephalogram (EEG) signals in formed of low-amplitude and polyspikes activity [Vargas et al., 2011]. Generally, this disease was examined through the brainwaves or EEG signals by clinical neurulogists. An EEG is a device to record the brainwaves in term of electrical activity from the brain. Brain patterns from wave shapes that are commonly sinusoidal and measured from peak to peak that range from 0.5 μV to 100 μV in amplitude. Moreover, the brainwaves have been categorized into four frequency bands, Beta (>13 Hz), Alpha (8-13 Hz), Theta (4-8 Hz) and Delta (0.5-4 Hz). All the frequency bands will be used to characterize the Epilepsy brainwave in terms of amplitude (voltage) and frequency [Mustafa et al., 2013]. The Epilepsy brainwaves were downloaded from http://www.vis.caltech.edu/~rodri/data.htm of Fp1 and Fp2 channels which is from rats. The brainwaves consists Epilepsy and non-Epilepsy samples. Then, the brainwaves were pre-processed to remove artefact (noise). Various methods had been introduced to detect spike-wave discharge in Epilepsy patient brainwave. Brainwave is nonstationary signal, therefore, time-frequency analysis is appropriate methods to analyse the signals[Tzallas et al., 2009, Vargas et al., 2011]. One of the most popular time-frequency analyses is ShortTime Fourier Transform (STFT). After the brainwaves were pre-processed, STFT was employed to the clean brainwaves. The STFT spectrogram was generated for four frequency bands of the samples

The Recognizability and Localizability of Auditory Alarms: Setting Global Medical Device Standards.

Objective Four sets of eight audible alarms matching the functions specified in IEC 60601-1-8 were designed using known principles from auditory cognition with the intention that they would be more recognizable and localizable than those currently specified in the standard. Background The audible alarms associated with IEC 60601-1-8, a global medical device standard, are known to be difficult to learn and retain, and there have been many calls to update them. There are known principles of design and cognition that might form the basis of more readily recognizable alarms. There is also scope for improvement in the localizability of the existing alarms. Method Four alternative sets of alarms matched to the functions specified in IEC 60601-1-8 were tested for recognizability and localizability and compared with the alarms currently specified in the standard. Results With a single exception, all prototype sets of alarms outperformed the current IEC set on both recognizability and localizability. Within the prototype sets, auditory icons were the most easily recognized, but the other sets, using word rhythms and simple acoustic metaphors, were also more easily recognized than the current alarms. With the exception of one set, all prototype sets were also easier to localize. Conclusion Known auditory cognition and perception principles were successfully applied to an existing audible alarm problem. Application This work constitutes the first (benchmarking) phase of replacing the alarms currently specified in the standard. The design principles used for each set demonstrate the relative ease with which different alarm types can be recognized and localized

Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital

Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in the Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated the potential of a panel of novel biomarkers (with enhanced liver expression or linked to the mechanisms of toxicity) to identify patients with acetaminophen-induced acute liver injury (ALI) at first presentation to the hospital when currently used markers are within the normal range. In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction). Receiver operator characteristic curve analysis and positive/negative predictive values were used to compare sensitivity to report liver injury versus alanine transaminase (ALT) and International Normalized Ratio (INR). In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR. In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose. Conclusion: Elevations in plasma miR-122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range. The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies

Neural predictors of treatment response to brain stimulation and psychological therapy in depression: a double-blind randomized controlled trial

Standard depression treatments, including antidepressant medication and cognitive behavioural therapy (CBT), are ineffective for many patients. Prefrontal transcranial direct current stimulation (tDCS) has been proposed as an alternative treatment, but has shown inconsistent efficacy for depression, and its mechanisms are poorly understood. We recruited unmedicated patients with major depressive disorder (N = 71 approached; N = 39 randomised) for a mechanistic, double-blind, randomized controlled trial consisting of eight weekly sessions of prefrontal tDCS administered to the left prefrontal cortex prior to CBT. We probed (1) whether tDCS improved the efficacy of CBT relative to sham stimulation; and (2) whether neural measures predicted clinical response. We found a modest and non-significant effect of tDCS on clinical outcome over and above CBT (active: 50%; sham: 31.6%; odds ratio: 2.16, 95% CI = 0.59–7.99), but a strong relationship, predicted a priori, between baseline activation during a working memory task in the stimulated prefrontal region and symptom improvement. Repeating our analyses of symptom outcome splitting the sample according to this biomarker revealed that tDCS was significantly superior to sham in individuals with high left prefrontal cortex activation at baseline; we also show 86% accuracy in predicting clinical response using this measure. Exploratory analyses revealed several other regions where activation at baseline was associated with subsequent response to CBT, irrespective of tDCS. This mechanistic trial revealed variable, but predictable, clinical effects of prefrontal tDCS combined with CBT for depression. We have discovered a potential explanation for this variability: individual differences in baseline activation of the region stimulated. Such a biomarker could potentially be used to pre-select patients for trials and, eventually, in the clinic.This work was supported by the Brain and Behavior Research Foundation (grant number 20162) to JPR and a Brain Research Trust PhD studentship awarded to CLN, and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre (SP). JPR consults for Cambridge Cognition, Takeda Ltd and GE

The Chandra Source Catalog

The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public ACIS imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents <~ 30''. The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports scientific analysis using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1 sigma uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of <~ 1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively.Comment: To appear in The Astrophysical Journal Supplement Series, 53 pages, 27 figure

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): PartA = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W