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A low‐cost, sensitive and specific PCR ‐based tool for rapid clinical detection of HLA‐B*35 alleles associated with delayed drug hypersensitivity reactions
Get PDFHLA (HLA) alleles are risk factors for CD8+ T-cell-mediated drug hypersensitivity reactions. However, as most HLA associations are incompletely predictive and/or involve risk alleles at low frequency, costly sequence-based typing can elude an economically productive cost: benefit ratio for clinical validation studies and diagnostic and/or preventative screening. Hence rapid and low-cost detection assays are now required, both for single alleles but also across risk loci associated with broader multi-disease risk; exemplified by associations with diverse alleles in HLA-B*35, including HLA-B*35:01 and green tea- or co-trimoxazole-induced liver injury. Here, we developed a cost-effective (<$10USD) qPCR assay for rapid (<2.5 h) clinical detection of HLA-B*35 alleles. The assay was validated using 430 DNA samples with previous American society for histocompatibility and immunogenetics-accredited sequence-based high-resolution HLA typing, positively detecting all HLA-B*35 allelic variants in our cohort, and as expected by primer design, the six samples that expressed low-frequency B*78:01. The assay did not result in positive detection for any negative control allele. With expected detection of B*35 and B*78, our assay sensitivity (95% CI, 95.07%–100.00%) and specificity (95% CI, 98.97%–100.00%) of 100% using as low as 10 ng of DNA provides a reliable HLA-B*35 screening tool for clinical validation and HLA–risk-based prevention and diagnostics
Direct low field J-edited diffusional proton NMR spectroscopic measurement of COVID-19 inflammatory biomarkers in human serum
Get PDFA JEDI NMR pulse experiment incorporating relaxational, diffusional and J-modulation peak editing has been implemented for a low field (80 MHz proton resonance frequency) spectrometer system to measure quantitatively two recently discovered plasma markers of SARS-CoV-2 infection and general inflammation. JEDI spectra capture a unique signature of two biomarker signals from acetylated glycoproteins (Glyc) and the supramolecular phospholipid composite (SPC) signals that are relatively enhanced by the combination of relaxation, diffusion and J-editing properties of the JEDI experiment that strongly attenuate contributions from the other molecular species in plasma. The SPC/Glyc ratio data were essentially identical in the 600 MHz and 80 MHz spectra obtained (R2 = 0.97) and showed significantly different ratios for control (n = 28) versus SARS-CoV-2 positive patients (n = 29) (p = 5.2 × 10−8 and 3.7 × 10−8 respectively). Simplification of the sample preparation allows for data acquisition in a similar time frame to high field machines (∼4 min) and a high-throughput version with 1 min experiment time could be feasible. These data show that these newly discovered inflammatory biomarkers can be measured effectively on low field NMR instruments that do not not require housing in a complex laboratory environment, thus lowering the barrier to clinical translation of this diagnostic technology
Biofuels as renewable reductants for the processing of ilmenite to produce synthetic rutile
No full textThis study assessed the technical feasibility of using biofuels as renewable reductants in the production of synthetic rutile (88–95% TiO2) from ilmenite (FeTiO3) by the Becher process. Three biofuels were evaluated—charcoal (CC), wood kindling (WK) and gum tree sticks (GTS)—for the quality of the synthetic rutile products that were produced from a representative ilmenite sample and compared with that of a Western Australian coal (WAC), which is typical of coals that are being used in this technology. The results show that the carbon content of the different reductants ranged from 46% each for GTS and WK to 82% for CC, compared with 58% for WAC. The renewable reductants yielded synthetic rutile products with TiO2 content between 93% for GTS and 95% each for CC and WK, compared with 94% for WAC. The iodine numbers of carbon residues from the reduction process were 900 each for WK, CC and GTS, while that of WAC was 700. Overall, these results indicate that biofuels could be alternatives to coal in the production of synthetic rutile from ilmenite
Allergy, inflammation, hepatopathy and coagulation biomarkers in dogs with suspected anaphylaxis due to insect envenomation
Get PDFObjectives: To compare concentrations of biomarkers of; allergy [mast cell tryptase (MCT) and histamine], inflammation [interleukin (IL)-6,-10, and−18, CXCL8, CCL2, keratinocyte chemoattractant (KC), C-reactive protein (CRP)], endothelial glycocalyx shedding (hyaluronan), coagulation [prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and von Willebrand Factor antigen, protein C (PC) and antithrombin (AT) activity], and hepatopathy [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin] between dogs with anaphylaxis after suspected insect exposure, dogs with critical illness, and healthy dogs.
Design: This was a single center prospective clinical observational comparative biomarker study that included 25 dogs with anaphylaxis (evidence of insect exposure, acute dermatological signs, and other organ involvement), 30 dogs with other critical illness, and 20 healthy dogs. Differences across groups in biomarker concentrations were tested using one-way ANOVA or Kruskal-Wallis test, with significant P values (<0.05) reported for pairwise differences detected by post-hoc tests. Logistic regression models were used to calculate the area under the receiver operator characteristic curve (AUROC) for discrimination between anaphylaxis and non-anaphylactic illness.
Results: Histamine concentration was significantly higher in the anaphylaxis group than the healthy (P < 0.001) and critically ill groups (P < 0.001), whereas no differences in MCT were detected amongst groups. Biomarker concentrations that were increased relative to healthy dogs in both the anaphylaxis and critically ill groups included IL-10 (P < 0.001 and P = 0.007, respectively), CCL2 (P = 0.007 and P < 0.001, respectively) and AST (both P < 0.001), whereas only the critically ill group had significantly increased CRP (P < 0.001), IL-6 (P < 0.001), KC (P < 0.001), ALP (P < 0.001), and fibrinogen (P = 0.016) concentrations, compared to the healthy group. Only dogs with anaphylaxis had significantly higher hyaluronan (P = 0.021) and ALT (P = 0.021) concentrations, and lower PC (P = 0.030) and AT (P = 0.032) activities, compared to healthy dogs. Both CRP and histamine concentration showed good discrimination between anaphylaxis and other critical illness, with an AUROC of 0.96 (95% CI 0.91–1) and 0.81 (95% CI 0.69–0.93), respectively.
Conclusions: This preliminary study in dogs with anaphylaxis after suspected insect exposure, found evidence of an early innate immune response, glycocalyx shedding and anticoagulant consumption. Both CRP and histamine showed potential clinical utility for differentiation between anaphylaxis and other critical illness
Hydrometallurgy
No full textHydrometallurgy: Theory provides the necessary fundamental background to the multidisciplinary field of hydrometallurgy, presenting the tools needed to utilize the theory to quantitatively describe, model and control the unit operations used in hydrometallurgical plants. The book describes the development and operation of processes utilizing hydrometallurgical operations, making it a valuable resource and reference for researchers, academics, students and industry professionals. It focuses on quantitative problem-solving with many worked examples and focused problems based on Nicol’s many years of experience in teaching hydrometallurgy to students, researchers and industry professionals
Osmopriming combined with Boron-Tolerant Bacteria (Bacillus sp. MN54) improved the productivity of Desi Chickpea under rainfed and irrigated conditions
Get PDFChickpeas are rich source of protein and predominantly grown in boron (B)-deficient sandy-loam soils in Pakistan. Boron-tolerant bacteria (BTB) could tolerate higher B levels in soil and increase B availability to the plants. Field trials were conducted under irrigated (district Layyah) and rainfed (district Chakwal) conditions to evaluate the interactive effects of pre-optimized B application methods and BTB (Bacillus sp. MN54) on the nodule’s population, grain quality, productivity, and grain-B concentration in desi chickpea during 2019–2020 and 2020–2021. Boron was applied as soil application (1 kg B ha−1), foliar application (0.025% B), osmopriming (0.001% B), and seed coating (1.5 g B kg−1 seed) with or without BTB inoculation. Untreated seeds receiving no B through any of the methods were regarded as control. The individual and interactive effects (up to three-way interaction of location × BTB inoculation × B application methods) of year, location, B application methods and BTB inoculation significantly altered the growth and yield-related traits of desi chickpea. The four-way interaction of year × location × BTB inoculation × B application methods was non-significant for all recorded growth and yield-related traits. Regarding individual effects, the higher values of growth and yield-related traits were noted for 2020–2021, rainfed location, BTB inoculation and B application through seed priming. Similarly, in two-way interactions 2020–2021 with rainfed location and BTB inoculation, rainfed location with BTB inoculation and osmopriming and osmopriming with BTB inoculation recorded higher values of the growth and yield-related traits. Osmopriming combined with BTB inoculation significantly improved dry matter accumulation and leaf area index in both locations. Boron application through all the methods significantly improved grain quality, yield grain B concentration. The highest grain and biological yields, and nodules’ population were recorded with osmopriming followed by soil application of B combined with BTB inoculation. The highest plant B concentration (75.05%) was recorded with foliar application of B followed by osmopriming (68.73%) combined with BTB inoculation. Moreover, the highest economic returns (USD 2068.5 ha−1) and benefit–cost ratio (3.7%) were recorded with osmopriming + BTB inoculation in 2020–2021 under rainfed conditions. Overall, B application through osmopriming and soil application combined with BTB inoculation could be used to increase productivity and profitability of desi chickpea, whereas foliar application is a better method to enhance grain and plant B concentration
Detection of filovirus-reactive antibodies in Australian bat species
Get PDFBats have been implicated as the reservoir hosts of filoviruses in Africa, with serological evidence of filoviruses in various bat species identified in other countries. Here, serum samples from 190 bats, comprising 12 different species, collected in Australia were evaluated for filovirus antibodies. An in-house indirect microsphere assay to detect antibodies that cross-react with Ebola virus (Zaire ebolavirus; EBOV) nucleoprotein (NP) followed by an immunofluorescence assay (IFA) were used to confirm immunoreactivity to EBOV and Reston virus (Reston ebolavirus; RESTV). We found 27 of 102 Yinpterochiroptera and 19 of 88 Yangochiroptera samples were positive to EBOV NP in the microsphere assay. Further testing of these NP positive samples by IFA revealed nine bat sera that showed binding to ebolavirus-infected cells. This is the first report of filovirus-reactive antibodies detected in Australian bat species and suggests that novel filoviruses may be circulating in Australian bats
Psychedelic forum member preferences for carer experience and consumption behavior: Can “Trip Sitters” Help Inform Psychedelic Harm Reduction Services?
No full textBackground:
There is limited research on the provision of harm reduction services to people who use psychedelics. Little is known about provision of care to people consuming psychedelics outside of clinical trials.
Methods:
We investigated how people who used psychedelics discussed their preferences for care (or “trip sitting”) on two online forums: The Shroomery and DMT Nexus. A thematic analysis of the discussion was conducted to better understand consumer preferences for harm reduction services and resources.
Results:
We identified two key themes: experience and remote sitting. Forum participants valued trip sitters who had experienced psychedelic and other non-ordinary states of consciousness, who had knowledge of the health and medical industry, psychedelic literature and/or had previously cared for other psychedelic consumers. Forum participants also identified the value of consuming a psychedelic without somebody who was in their physical proximity, through communicating their plans to a remote trip sitter. The use of online tools was identified as a way to maximize the benefit of privacy while retaining carer benefits.
Conclusion:
Demand for trip sitters with lived psychedelic experience is likely influenced by stigma and empathy. Trip sitters who could relate to the effects of psychedelics assisted consumers in avoiding stigma while vulnerable under the effects of psychedelics. As such, psychedelic harm reduction services should be delivered by peers to ensure care maximizes the benefits of empathy. Psychedelic harm reduction services should consider how remote workers could be employed. There is a clear demand for remote psychedelic care services and to our knowledge this has not yet been explored
Improving voltage regulation and unbalance in distribution networks using Peer-to-Peer data sharing between Single-Phase PV Inverters
No full textThis paper proposes a novel reactive power-based control strategy for single-phase PV inverters (PVIs) to simultaneously improve voltage unbalance (VU) and voltage regulation (VR) in low-voltage distribution networks. The proposed strategy relies on communication links between neighboring PVIs to exchange limited data. In this strategy, each PVI finds communication paths between itself and the closest neighboring ones connected to other phases. Then, using the obtained paths and the maximum and the minimum voltage magnitude of the grid, PVIs improve both VU and VR at the same time. The performance of the proposed control strategy is evaluated by various simulation studies using the IEEE European low-voltage test feeder and considering different operational conditions. In addition, the impacts of moving clouds and a failure in the communication links have been assessed. The simulation results exhibit that using the proposed control strategy, the voltage magnitude of all the nodes will remain within the allowed limits and at the same time, the phase voltage unbalance factor will be also significantly improved
Forecasting photovoltaic power generation with a stacking ensemble model
Get PDFNowadays, photovoltaics (PV) has gained popularity among other renewable energy sources because of its excellent features. However, the instability of the system’s output has become a critical problem due to the high PV penetration into the existing distribution system. Hence, it is essential to have an accurate PV power output forecast to integrate more PV systems into the grid and to facilitate energy management further. In this regard, this paper proposes a stacked ensemble algorithm (Stack-ETR) to forecast PV output power one day ahead, utilizing three machine learning (ML) algorithms, namely, random forest regressor (RFR), extreme gradient boosting (XGBoost), and adaptive boosting (AdaBoost), as base models. In addition, an extra trees regressor (ETR) was used as a meta learner to integrate the predictions from the base models to improve the accuracy of the PV power output forecast. The proposed model was validated on three practical PV systems utilizing four years of meteorological data to provide a comprehensive evaluation. The performance of the proposed model was compared with other ensemble models, where RMSE and MAE are considered the performance metrics. The proposed Stack-ETR model surpassed the other models and reduced the RMSE by 24.49%, 40.2%, and 27.95% and MAE by 28.88%, 47.2%, and 40.88% compared to the base model ETR for thin-film (TF), monocrystalline (MC), and polycrystalline (PC) PV systems, respectively