Projected expansion of Trichodesmium’s geographical distribution and increase of growth potential in response to climate change

Estimates of marine N₂ fixation range from 52 to 73 Tg N yr‾¹, of which we calculate up to 84% is from Trichodesmium based on previous measurements of nifH gene abundance and our new model of Trichodesmium growth. Here we assess the likely effects of four major climate change‐related abiotic factors on the spatiotemporal distribution and growth potential of Trichodesmium for the last glacial maximum (LGM), the present (2006‐2015) and the end of this century (2100) by mapping our model of Trichodesmium growth onto inferred global surface ocean fields of pCO₂, temperature, light and Fe. We conclude that growth rate was severely limited by low pCO₂ at the LGM, that current pCO₂ levels do not significantly limit Trichodesmium growth and thus, the potential for enhanced growth from future increases of CO₂ is small. We also found that the area of the ocean where sea surface temperatures (SST) are within Trichodesmium’s thermal niche increased by 32% from the LGM to present, but further increases in SST due to continued global warming will reduce this area by 9%. However, the range reduction at the equator is likely to be offset by enhanced growth associated with expansion of regions with optimal or near optimal Fe and light availability. Between now and 2100, the ocean area of optimal SST and irradiance is projected to increase by 7%, and the ocean area of optimal SST, irradiance and iron is projected to increase by 173%. Given the major contribution of this keystone species to annual N₂ fixation and thus pelagic ecology, biogeochemistry and CO₂ sequestration, the projected increase in the geographical range for optimal growth could provide a negative feedback to increasing atmospheric CO₂ concentrations

Review of Antimicrobial Nanocoatings in Medicine and Dentistry: Mechanisms of Action, Biocompatibility Performance, Safety, and Benefits Compared to Antibiotics

This review discusses topics relevant to the development of antimicrobial nanocoatings and nanoscale surface modifications for medical and dental applications. Nanomaterials have unique properties compared to their micro- and macro-scale counterparts and can be used to reduce or inhibit bacterial growth, surface colonization and biofilm development. Generally, nanocoatings exert their antimicrobial effects through biochemical reactions, production of reactive oxygen species or ionic release, while modified nanotopographies create a physically hostile surface for bacteria, killing cells via biomechanical damage. Nanocoatings may consist of metal nanoparticles including silver, copper, gold, zinc, titanium, and aluminum, while nonmetallic compounds used in nanocoatings may be carbon-based in the form of graphene or carbon nanotubes, or composed of silica or chitosan. Surface nanotopography can be modified by the inclusion of nanoprotrusions or black silicon. Two or more nanomaterials can be combined to form nanocomposites with distinct chemical or physical characteristics, allowing combination of different properties such as antimicrobial activity, biocompatibility, strength, and durability. Despite their wide range of applications in medical engineering, questions have been raised regarding potential toxicity and hazards. Current legal frameworks do not effectively regulate antimicrobial nanocoatings in matters of safety, with open questions remaining about risk analysis and occupational exposure limits not considering coating-based approaches. Bacterial resistance to nanomaterials is also a concern, especially where it may affect wider antimicrobial resistance. Nanocoatings have excellent potential for future use, but safe development of antimicrobials requires careful consideration of the "One Health" agenda, appropriate legislation, and risk assessment

Pharmacokinetic-Pharmacodynamic Modelling of the Analgesic and Antihyperalgesic Effects of Morphine after Intravenous Infusion in Human Volunteers

Using a modelling approach, this study aimed to (i) examine whether the pharmacodynamics of the analgesic and antihyperalgesic effects of morphine differ; (ii) investigate the influence of demographic, pain sensitivity and genetic (OPRM1) variables on between-subject variability of morphine pharmacokinetics and pharmacodynamics in human experimental pain models. The study was a randomized, double-blind, 5-arm, cross-over, placebo-controlled study. The psychophysical cutaneous pain tests, electrical pain tolerance (EPTo) and secondary hyperalgesia areas (2HA) were studied in 28 healthy individuals (15 males). The subjects were chosen based on a previous trial where 100 subjects rated (VAS) their pain during a heat injury (47°C, 7 min., 12.5 cm²). The 33% lowest- and highest pain-sensitive subjects were offered participation in the present study. A two-compartment linear model with allometric scaling for weight provided the best description of the plasma concentration-time profile of morphine. Changes in the EPTo and 2HA responses with time during the placebo treatment were best described by a linear model and a quadratic model, respectively. The model discrimination process showed clear evidence for adding between-occasion variability (BOV) on baseline and the placebo slope for EPTo and 2HA, respectively. The sensitivity covariate was significant on baseline EPTo values and genetics as a covariate on the placebo slope for 2HA. The analgesic and antihyperalgesic effects of morphine were pharmacologically distinct as the models had different effect site equilibration half-lives and different covariate effects. Morphine had negligible effect on 2HA, but significant effect on EPTo.Pernille Ravn, David J.R. Foster, Mads Kreilgaard, Lona Christrup, Mads U. Werner, Erik L. Secher, Ulrik Skram and Richard Upto

Gated pipelined folding ADC based low power sensor for large-scale radiometric partial discharge monitoring

Partial discharge is a well-established metric for condition assessment of high-voltage plant equipment. Traditional techniques for partial discharge detection involve physical connection of sensors to the device under observation, limiting sensors to monitoring of individual apparatus, and therefore, limiting coverage. Wireless measurement provides an attractive low-cost alternative. The measurement of the radiometric signal propagated from a partial discharge source allows for multiple plant items to be observed by a single sensor, without any physical connection to the plant. Moreover, the implementation of a large-scale wireless sensor network for radiometric monitoring facilitates a simple approach to high voltage fault diagnostics. However, accurate measurement typically requires fast data conversion rates to ensure accurate measurement of faults. The use of high-speed conversion requires continuous high-power dissipation, degrading sensor efficiency and increasing cost and complexity. Thus, we propose a radiometric sensor which utilizes a gated, pipelined, sample-and-hold based folding analogue-todigital converter structure that only samples when a signal is received, reducing the power consumption and increasing the efficiency of the sensor. A proof of concept circuit has been developed using discrete components to evaluate the performance and power consumption of the system

NMDA-receptor antibodies alter cortical microcircuit dynamics

NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities-or even seizures-is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in pediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab-related changes render microcircuitry critically susceptible to overt EEG paroxysms when these key parameters are changed, even though the same parameter fluctuations are tolerated in the in silico model of the control condition. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Evaluation of the methodological quality of studies of the performance of diagnostic tests for bovine tuberculosis using QUADAS

There has been little assessment of the methodological quality of studies measuring the performance (sensitivity and/or specificity) of diagnostic tests for animal diseases. In a systematic review, 190 studies of tests for bovine tuberculosis (bTB) in cattle (published 1934-2009) were assessed by at least one of 18 reviewers using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) checklist adapted for animal disease tests. VETQUADAS (VQ) included items measuring clarity in reporting (n = 3), internal validity (n = 9) and external validity (n = 2). A similar pattern for compliance was observed in studies of different diagnostic test types. Compliance significantly improved with year of publication for all items measuring clarity in reporting and external validity but only improved in four of the nine items measuring internal validity (p < 0.05). 107 references, of which 83 had performance data eligible for inclusion in a meta-analysis were reviewed by two reviewers. In these references, agreement between reviewers' responses was 71% for compliance, 32% for unsure and 29% for non-compliance. Mean compliance with reporting items was 2, 5.2 for internal validity and 1.5 for external validity. The index test result was described in sufficient detail in 80.1% of studies and was interpreted without knowledge of the reference standard test result in only 33.1%. Loss to follow-up was adequately explained in only 31.1% of studies. The prevalence of deficiencies observed may be due to inadequate reporting but may also reflect lack of attention to methodological issues that could bias the results of diagnostic test performance estimates. QUADAS was a useful tool for assessing and comparing the quality of studies measuring the performance of diagnostic tests but might be improved further by including explicit assessment of population sampling strategy.The SE3238 project “Meta-analysis of diagnostic tests and modelling to identify appropriate testing strategies to reduce M. bovis infection in GB herds” was funded by the UK Department for Environment, Food and Rural Affairs (Defra).http://www.elsevier.com/locate/prevetmedam2018Veterinary Tropical Disease