Disposable MMP-9 sensor based on the degradation of peptide cross-linked hydrogel films using electrochemical impedance spectroscopy

Barts and The London Charity and Queen Mary Innovation Lt

Peptide Cross-Linked Poly(2-oxazoline) as a Sensor Material for the Detection of Proteases with a Quartz Crystal Microbalance

Inflammatory conditions are frequently accompanied by increased levels of active proteases, and there is rising interest in methods for their detection to monitor inflammation in a point of care setting. In this work, new sensor materials for disposable single-step protease biosensors based on poly(2-oxazoline) hydrogels cross-linked with a protease-specific cleavable peptide are described. The performance of the sensor material was assessed targeting the detection of matrix metalloproteinase-9 (MMP-9), a protease that has been shown to be an indicator of inflammation in multiple sclerosis and other inflammatory conditions. Films of the hydrogel were formed on gold-coated quartz crystals using thiol–ene click chemistry, and the cross-link density was optimized. The degradation rate of the hydrogel was monitored using a quartz crystal microbalance (QCM) and showed a strong dependence on the MMP-9 concentration. A concentration range of 0–160 nM of MMP-9 was investigated, and a lower limit of detection of 10 nM MMP-9 was determined

Modelling the long-term carbon cycle, atmospheric CO2, and Earth surface temperature from late Neoproterozoic to present day

Over geological timescales, CO2 levels are determined by the operation of the long term carbon cycle, and it is generally thought that changes in atmospheric CO2 concentration have controlled variations in Earth's surface temperature over the Phanerozoic Eon. Here we compile independent estimates for global average surface temperature and atmospheric CO2 concentration, and compare these to the predictions of box models of the long term carbon cycle COPSE and GEOCARBSULF. We find a strong relationship between CO2 forcing and temperature from the proxy data, for times where data is available, and we find that current published models reproduce many aspects of CO2 change, but compare poorly to temperature estimates. Models are then modified in line with recent advances in understanding the tectonic controls on carbon cycle source and sink processes, with these changes constrained by modelling 87Sr/86Sr ratios. We estimate CO2 degassing rates from the lengths of subduction zones and rifts, add differential effects of erosion rates on the weathering of silicates and carbonates, and revise the relationship between global average temperature changes and the temperature change in key weathering zones. Under these modifications, models produce combined records of CO2 and temperature change that are reasonably in line with geological and geochemical proxies (e.g. central model predictions are within the proxy windows for >~75% of the time covered by data). However, whilst broad long-term changes are reconstructed, the models still do not adequately predict the timing of glacial periods. We show that the 87Sr/86Sr record is largely influenced by the weathering contributions of different lithologies, and is strongly controlled by erosion rates, rather than being a good indicator of overall silicate chemical weathering rates. We also confirm that a combination of increasing erosion rates and decreasing degassing rates over the Neogene can cause the observed cooling and Sr isotope changes without requiring an overall increase in silicate weathering rates. On the question of a source or sink dominated carbon cycle, we find that neither alone can adequately reconstruct the combination of CO2, temperature and strontium isotope dynamics over Phanerozoic time, necessitating a combination of changes to sources and sinks. Further progress in this field relies on >108 year dynamic spatial reconstructions of ancient tectonics, paleogeography and hydrology. Whilst this is a significant challenge, the latest reconstruction techniques, proxy records and modelling advances make this an achievable target

Sex-Specific Differences in Shoaling Affect Parasite Transmission in Guppies

Background: Individuals have to trade-off the costs and benefits of group membership during shoaling behaviour. Shoaling can increase the risk of parasite transmission, but this cost has rarely been quantified experimentally. Guppies (Poecilia reticulata) are a model system for behavioural studies, and they are commonly infected by gyrodactylid parasites, notorious fish pathogens that are directly transmitted between guppy hosts. Methodology/Principal Findings:Parasite transmission in single sex shoals of male and female guppies were observed using an experimental infection of Gyrodactylus turnbulli. Parasite transmission was affected by sex-specific differences in host behaviour, and significantly more parasites were transmitted when fish had more frequent and more prolonged contact with each other. Females shoaled significantly more than males and had a four times higher risk to contract an infection. Conclusions/Significance: Intersexual differences in host behaviours such as shoaling are driven by differences in natural and sexual selection experienced by both sexes. Here we show that the potential benefits of an increased shoaling tendency are traded off against increased risks of contracting an infectious parasite in a group-living species

WebCARMA: a web application for the functional and taxonomic classification of unassembled metagenomic reads

Gerlach W, Jünemann S, Tille F, Goesmann A, Stoye J. WebCARMA: a web application for the functional and taxonomic classification of unassembled metagenomic reads. BMC Bioinformatics. 2009;10(1):430.Background Metagenomics is a new field of research on natural microbial communities. High-throughput sequencing techniques like 454 or Solexa-Illumina promise new possibilities as they are able to produce huge amounts of data in much shorter time and with less efforts and costs than the traditional Sanger technique. But the data produced comes in even shorter reads (35-100 basepairs with Illumina, 100-500 basepairs with 454-sequencing). CARMA is a new software pipeline for the characterisation of species composition and the genetic potential of microbial samples using short, unassembled reads. Results In this paper, we introduce WebCARMA, a refined version of CARMA available as a web application for the taxonomic and functional classification of unassembled (ultra-)short reads from metagenomic communities. In addition, we have analysed the applicability of ultra-short reads in metagenomics. Conclusions We show that unassembled reads as short as 35 bp can be used for the taxonomic classification of a metagenome. The web application is freely available at http://webcarma.cebitec.uni-bielefeld.d

Multicenter evaluation of a lateral-flow device test for diagnosing invasive pulmonary aspergillosis in ICU patients.

Published onlineClinical TrialJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tINTRODUCTION: The incidence of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is increasing, and early diagnosis of the disease and treatment with antifungal drugs is critical for patient survival. Serum biomarker tests for IPA typically give false-negative results in non-neutropenic patients, and galactomannan (GM) detection, the preferred diagnostic test for IPA using bronchoalveolar lavage (BAL), is often not readily available. Novel approaches to IPA detection in ICU patients are needed. In this multicenter study, we evaluated the performance of an Aspergillus lateral-flow device (LFD) test for BAL IPA detection in critically ill patients. METHODS: A total of 149 BAL samples from 133 ICU patients were included in this semiprospective study. Participating centers were the medical university hospitals of Graz, Vienna and Innsbruck in Austria and the University Hospital of Mannheim, Germany. Fungal infections were classified according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: Two patients (four BALs) had proven IPA, fourteen patients (sixteen BALs) had probable IPA, twenty patients (twenty-one BALs) had possible IPA and ninety-seven patients (one hundred eight BALs) did not fulfill IPA criteria. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratios for diagnosing proven and probable IPA using LFD tests of BAL were 80%, 81%, 96%, 44% and 17.6, respectively. Fungal BAL culture exhibited a sensitivity of 50% and a specificity of 85%. CONCLUSION: LFD tests of BAL showed promising results for IPA diagnosis in ICU patients. Furthermore, the LFD test can be performed easily and provides rapid results. Therefore, it may be a reliable alternative for IPA diagnosis in ICU patients if GM results are not rapidly available. TRIAL REGISTRATION: ClinicalTrials.gov NCT02058316. Registered 20 January 2014.PfizerOesterreichische Nationalbank (Anniversary Fund, project number 15346)

Congenital Plasmodium vivax malaria mimicking neonatal sepsis: a case report

Although malaria in pregnancy can cause very significant neonatal morbidity, congenital malaria is a very rare condition in both endemic and non-endemic areas. A case of congenital malaria by Plasmodium vivax, initially mistaken for neonatal sepsis, is described. The correct diagnosis was accidentally done, as congenital malaria had been missed in the initial differential diagnosis

Hypofractionated radiotherapy for prostate cancer

In the last few years, hypofractionated external beam radiotherapy has gained increasing popularity for prostate cancer treatment, since sufficient evidence exists that prostate cancer has a low alpha/beta ratio, lower than the one of the surrounding organs at risk and thus there is a potential therapeutic benefit of using larger fractionated single doses. Apart from the therapeutic rationale there are advantages such as saving treatment time and medical resources and thereby improving patient's convenience. While older trials showed unsatisfactory results in both standard and hypofractionated arm due to insufficient radiation doses and non-standard contouring of target volumes, contemporary randomized studies have reported on encouraging results of tumor control mostly without an increase of relevant side effects, especially late toxicity. Aim of this review is to give a detailed analysis of relevant, recently published clinical trials with special focus on rationale for hypofractionation and different therapy settings

Nonlinear dynamics and chaos in an optomechanical beam

[EN] Optical nonlinearities, such as thermo-optic mechanisms and free-carrier dispersion, are often considered unwelcome effects in silicon-based resonators and, more specifically, optomechanical cavities, since they affect, for instance, the relative detuning between an optical resonance and the excitation laser. Here, we exploit these nonlinearities and their intercoupling with the mechanical degrees of freedom of a silicon optomechanical nanobeam to unveil a rich set of fundamentally different complex dynamics. By smoothly changing the parameters of the excitation laser we demonstrate accurate control to activate two-and four-dimensional limit cycles, a period-doubling route and a six-dimensional chaos. In addition, by scanning the laser parameters in opposite senses we demonstrate bistability and hysteresis between two-and four-dimensional limit cycles, between different coherent mechanical states and between four-dimensional limit cycles and chaos. Our findings open new routes towards exploiting silicon-based optomechanical photonic crystals as a versatile building block to be used in neurocomputational networks and for chaos-based applications.This work was supported by the European Comission project PHENOMEN (H2020-EU-713450), the Spanish Severo Ochoa Excellence program and the MINECO project PHENTOM (FIS2015-70862-P). DNU, PDG and MFC gratefully acknowledge the support of a Ramon y Cajal postdoctoral fellowship (RYC-2014-15392), a Beatriu de Pinos postdoctoral fellowship (BP-DGR 2015 (B) and a Severo Ochoa studentship, respectively. We would like to acknowledge Jose C. Sabina de Lis, J.M. Plata Suarez, A. Trifonova and C. Masoller for fruitful discussions.Navarro-Urrios, D.; Capuj, NE.; Colombano, MF.; García, PD.; Sledzinska, M.; Alzina, F.; Griol Barres, A.... (2017). Nonlinear dynamics and chaos in an optomechanical beam. Nature Communications. 8. https://doi.org/10.1038/ncomms14965S8Strogatz, S. H. 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Examination and measurement of coping among adolescents with spinal cord injury

Objectives: To describe coping strategy use in adolescents with spinal cord injury (SCI), to explore the underlying factor structure of a measure of coping among adolescents with SCI and to assess relationships between coping and psychosocial outcomes. Setting: Multiple pediatric SCI centers in the United States. Methods: One hundred and eighty-two participants aged 13–17 years who experienced an SCI completed measures including the Kidcope, Children’s Depression Inventory, Revised Children’s Manifest Anxiety Scale and the Pediatric Quality of Life Inventory. Results: Participants reported that cognitive restructuring and resignation are the most used coping strategies, whereas social support, emotional regulation (calming) and cognitive restructuring are the most effective coping strategies. An exploratory factor analysis revealed that a three-factor solution provided the most parsimonious model for the relationships between the different coping strategies. However, only one of the three factors had acceptable internal consistency. This factor comprised escape-oriented coping strategies or an avoidant approach to coping with the sequelae of SCI. After controlling for demographic/injury-related factors, higher scores on the escape-oriented factor were associated with the lower quality of life and higher levels of depression and anxiety symptomatology. Conclusion: Escape-oriented coping is associated with maladaptive psychosocial outcomes in adolescents with SCI. These adolescents report that active coping strategies are most effective in reducing SCI-related distress. Coping strategy use may mediate psychosocial outcomes in adolescents with SCI and represent an intervention target in adolescents who overly rely on escape-oriented coping