Development of a Clinical MALDI-ToF Mass Spectrometry Assay for SARS-CoV-2: Rational Design and Multi-Disciplinary Team Work.

The COVID-19 pandemic caused by the SARS-CoV-2 coronavirus has stretched national testing capacities to breaking points in almost all countries of the world. The need to rapidly screen vast numbers of a country's population in order to control the spread of the infection is paramount. However, the logistical requirement for reagent supply (and associated cost) of RT-PCR based testing (the current front-line test) have been hugely problematic. Mass spectrometry-based methods using swab and gargle samples have been reported with promise, but have not approached the task from a systematic analysis of the entire diagnostic process. Here, the pipeline from sample processing, the biological characteristics of the pathogen in human biofluid, the downstream bio- and physical-chemistry and the all-important data processing with clinical interpretation and reporting, are carefully compiled into a single high-throughput and reproducible rapid process. Utilizing MALDI-ToF mass spectrometric detection to viral envelope glycoproteins in a systems biology-multidisciplinary team approach, we have achieved a multifaceted clinical MALDI ToF MS screening test, primarily (but not limited to) SARS-CoV-2, with direct application to other future epidemics/pandemics that may arise. The clinical information generated not only includes SARS-CoV-2 coronavirus detection-(Spike protein fragments S1, S2b, S2a peaks), but other respiratory viral infections detected as well as an assessment of generalised oral upper respiratory immune response (elevated total Ig light chain peak) and a measure of the viral immune response (elevated intensity of IgA heavy chain peak). The advantages of the method include; (1) ease of sampling, (2) speed of analysis, and much reduced cost of testing. These features reveal the diagnostic utility of MALDI-ToF mass spectrometry as a powerful and economically attractive global solution

The impact of bar origin and morphology on stellar migration

Different mechanisms driving bar structure formation indicate that bar origins should be distinguishable in the stellar populations of galaxies. To study how these origins affect different bar morphologies and impact stellar orbits and migration, we analyse three simulated discs which are representative of bar formation under isolated evolution motivated by disc instability, and interaction driven tidal development. The first isolated disc and the tidally driven disc produce similar bar structure, while the second isolated disc, generated by the tidal initial condition without the companion, is visibly dissimilar. Changes to radial and vertical positions, angular momentum in the disc-plane, orbital eccentricity and the subsequent disc metallicities are assessed, as is the dependence on stellar age and formation radii. Bar origin is distinguishable, with the tidal disc displaying larger migration overall, higher metallicity difference between the inner and outer disc, as well as a population of inner disc stars displaced to large radii and below the disc-plane. The affect of closest approach on populations of stars formed before, after and during this period is evident. However, bar morphology is also found to be a significant factor in the evolution of disc stellar properties, with similar bars producing similar traits in migration tendency with radius, particularly in vertical stellar motion and in the evolution of central metallicity features

A microfluidic atmospheric-pressure plasma reactor for water treatment

A dielectric barrier discharge microfluidic plasma reactor, operated at atmospheric pressure, was studied for its potential to treat organic contaminants in water. Microfluidic technology represents a compelling approach for plasma-based water treatment due to inherent characteristics such as a large surface-area-to-volume ratio and flow control, in inexpensive and portable devices. The microfluidic device in this work incorporated a dielectric barrier discharge generated in a continuous gas flow stream of a two-phase annular flow regime in the microchannels of the device. Methylene blue in solution was used to investigate plasma induced degradation of dissolved organic compounds within the microfluidic device. The relative degradation rates of methylene blue were influenced by the residence time of the sample solution in the discharge zone, type of gas applied, channel depth and flow rate. Increasing the residence time inside the plasma region led to higher levels of degradation. Oxygen was found to be the most effective gas, with the spectra obtained using Liquid Chromatography-Mass Spectroscopy indicating the most significant degradation. By reducing the channel depth from 100 to 50 µm, the best results were obtained, achieving a greater than 97% level of methylene blue degradation. The microfluidic system presented here demonstrates proof-of-concept that plasma technology can be utilised as an advanced oxidation process for water treatment, with the potential to eliminate water treatment consumables such as filters and disinfectants

Implementación de un tren motriz eléctrico brushless para un prototipo ligero de bajo consumo energético tipo monoplaza

En los últimos años se han realizado investigaciones acerca del cambio climático y su impacto en los países latinoamericanos. El acuerdo de París indica que en los próximos años hasta el 2030 el aumento de temperatura ascendería a 1.5 °C. Sin embargo, los últimos estudios e investigaciones realizadas por el Instituto Geofísico del Ecuador indica que el calentamiento global asciende de manera acelerada, lo cual es perjudicial para la vida en el planeta. Esto se debe a que se esperaba, que para el año 2100 el aumento sería máximo hasta los de 2.0 °C. Un factor importante para este acontecimiento es la contaminación y gases de efecto invernadero provocados por medios de transporte que usan combustibles fósiles, además se tiene como evidencia un incremento entre el 15% y 20% en emisiones de gases contaminantes como el CO2 o dióxido de carbono. Estas emisiones de gases contaminantes afectan a la atmósfera terrestre, deteriora edificios, daña la materia prima de la población, la vida animal y vegetal. Para encontrar una respuesta a los problemas se ha propuesto la fabricación de un prototipo eléctrico junto a su implementación de propulsión eléctrica para cumplir con un objetivo que es la optimización de energía renovable y la reducción de contaminación en el aire. Se puede destacar que las energías renovables seguramente serán el presente y el futuro para el desarrollo mundial, ofreciendo ventajas como son la reducción a los niveles de emisiones de gases contaminantes que provienen de los vehículos que utilizan motores a gasolina o diésel. En el informe presentado por el Instituto Geofísico del Ecuador indica que las energías renovables en el año 2019 representaron más del 70% de la capacidad energética mundial ofreciendo así una opción buena y rentable para la reducción de contaminación. El prototipo eléctrico genera cero emisiones contaminantes convirtiéndose en una buena opción para el uso incorrecto de restos peligrosos para la salud como son refrigerantes, aceites o desengrasantes.In recent years, research has been conducted on climate change and its impact on Latin American countries. According to the Paris agreement, it indicates that in the coming years until 2030 the temperature increase would amount to 1.5 °C. However, the latest studies and research indicate that global warming is accelerating, which is detrimental to life on the planet because it was expected that by the year 2100 the increase would be a maximum of 2.0 °C. An important factor is transportation, which accounts for between 15% and 20%of the emissions of the most polluting gases, obviously CO2 is the main polluting factor here. This is due to the various emissions caused by engines with combustion chambers that are a risk to health and life in general. These emissions of polluting gases affect the earth's atmosphere, deteriorate buildings, raw materials, animal and plant life. To find an answer to these problems, it has been proposed the manufacture of a prototype and implementation of a brushless electric power to train for the optimization of renewable energy and thus find the pollution in the air, in addition to reduce diseases caused by pollution. It can be highlighted that renewable energies will surely be the present and the future for the global development of all types of energies, reducing considerably the levels of emissions coming from polluting vehicles or gasoline or diesel engines. In the report presented by internationally known companies focused on effectively renewable energies in the year 2019, this type of energies represented more than 70% of world energy capacity thus concluding one of the sources destined to become more profitable electricity for the planet and its circular economic development, wishing to meet objectives and commitments with the present project. The electric prototype generates zero emissions that cause the greenhouse effect that are generated from the batteries that feed the engine and obviously its fuel. Finally, they are a good option because they require less polluting substances such as oils, coolants, degreasers, etc

Impacts of past occupational injury and long-duration compensated work disability on future hospital admissions.

Objectives To investigate changes in the prevalence and nature of hospital admissions towards the end of long-duration workers’ compensation claims (>2 years), and afterwards. To examine differences in hospitalisation when workers’ compensation claims end due to either a 260-week duration limit, or otherwise, and comparisons with hospitalisations of a community comparator. Approach A retrospective cohort study examined 2475 workers, termed the s39 group, whose workers’ compensation ceased due to a 260-week limit in 2017/2018 under s39(1) of the Workers’ Compensation Act New South Wales 2012 legislative amendments (Australia). Comparator groups were injured workers with long-duration claims whose compensation ceased independently of s39 (termed the injured control group, N=3626) and a community group (N=8485). Workers’ compensation records were linked to national social security payments, and hospital admissions. Outcomes describe the prevalence and diagnostic categories of hospital admissions 12 months before, and after, the cessation of workers’ compensation stopped payments. Results Musculoskeletal health conditions were common diagnoses in overnight hospitalisations for injured workers. Single-day hospital care for mental health disorders were more common for injured workers (17% of same-day admissions) than for members of a community control (3% of same-day admissions) across two years. Exiting the workers’ compensation scheme is associated with significantly fewer annual hospital admissions for the injured control group (OR 0.76), but not for the s39 group (OR 1.01). Injured workers with long-duration compensated work disability were admitted to hospital more often than the community comparator group during the year after workers’ compensation stops (s39 group: OR 1.55, injured control group: OR 1.30). Across all study groups, hospital admission was more common for people receiving disability social security benefits and older age groups. Conclusion Policy change in the New South Wales workers’ compensation system introduced a 260-week limit on compensation, leaving workers with an elevated need for hospital care after their compensation ended. Welfare policies that disrupt key determinants of health require dedicated inter-agency provisions to support the elevated health needs of those affected

Shades of empire: police photography in German South-West Africa

This article looks at a photographic album produced by the German police in colonial Namibia just before World War I. Late 19th- and early 20th-century police photography has often been interpreted as a form of visual production that epitomized power and regimes of surveillance imposed by the state apparatuses on the poor, the criminal and the Other. On the other hand police and prison institutions became favored sites where photography could be put at the service of the emergent sciences of the human body—physiognomy, anthropometry and anthropology. While the conjuncture of institutionalized colonial state power and the production of scientific knowledge remain important for this Namibian case study, the article explores a slightly different set of questions. Echoing recent scholarship on visuality and materiality the photographic album is treated as an archival object and visual narrative that was at the same time constituted by and constitutive of material and discursive practices within early 20th-century police and prison institutions in the German colony. By shifting attention away from image content and visual codification alone toward the question of visual practice the article traces the ways in which the photo album, with its ambivalent, unstable and uncontained narrative, became historically active and meaningful. Therein the photographs were less informed by an abstract theory of anthropological and racial classification but rather entrenched with historically contingent processes of colonial state constitution, socioeconomic and racial stratification, and the institutional integration of photography as a medium and a technology into colonial policing. The photo album provides a textured sense of how fragmented and contested these processes remained throughout the German colonial period, but also how photography could offer a means of transcending the limits and frailties brought by the realities on the ground.International Bibliography of Social Science

The climatic impact‐driver framework for assessment of risk‐relevant climate information

The climate science and applications communities need a broad and demand-driven concept to assess physical climate conditions that are relevant for impacts on human and natural systems. Here, we augment the description of the “climatic impact-driver” (CID) approach adopted in the Working Group I (WGI) contribution to the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Report. CIDs are broadly defined as “physical climate system conditions (e.g., means, events, and extremes) that affect an element of society or ecosystems. Depending on system tolerance, CIDs and their changes can be detrimental, beneficial, neutral, or a mixture of each across interacting system elements and regions.” We give background information on the IPCC Report process that led to the development of the 7 CID types (heat and cold, wet and dry, wind, snow and ice, coastal, open ocean, and other) and 33 distinct CID categories, each of which may be evaluated using a variety of CID indices. This inventory of CIDs was co-developed with WGII to provide a useful collaboration point between physical climate scientists and impacts/risk experts to assess the specific climatic phenomena driving sectoral responses and identify relevant CID indices within each sector. The CID Framework ensures that a comprehensive set of climatic conditions informs adaptation planning and risk management and may also help prioritize improvements in modeling sectoral dynamics that depend on climatic conditions. CIDs contribute to climate services by increasing coherence and neutrality when identifying and communicating relevant findings from physical climate research to risk assessment and planning activities

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies