Trends in flame retardant levels in upholstered furniture and children's consumer products after regulatory action in California.

In 2013, California revised its upholstered furniture flammability standard TB 117-2013 to improve fire safety without the need for flame retardant (FR) chemicals. Subsequent legislation (SB 1019) required disclosure of FR content. In 2020 California expanded restriction on FR chemicals to include juvenile products and upholstered furniture (AB 2998). To monitor trends in FR use, and assess the effectiveness of the new regulations, we analyzed 346 samples from upholstered furniture (n = 270) and children's consumer products (n = 76), collected pre- and post-regulatory intervention for added FR chemicals (i.e., ∑FR > 1000 mg/kg). Upholstered furniture samples, collected from products before enactment of the new regulations, had a median FR concentration of 41,600 mg/kg (range: 1360-92,900 mg/kg), with 100% of the foam samples and 13.7% of the textile samples containing ∑FR > 1000 mg/kg. Firemaster formulations (FM 550 and FM 600), a mixture of triphenyl phosphate (TPHP), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (BEH-TEBP) and a mixture of isopropyl- or tert-butyl-triphenyl phosphates (ITPs or TBPPs), were the most frequently detected FR (34%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCIPP; 25%), TPHP with a mixture of polybrominated diphenyl ethers (BDE-47, 99, 100, 153 and 154; 20%) and tris(2-chloroethyl) phosphate (TCEP; 11%). Upholstered furniture components collected after enactment of the new legislation had a median FR concentration of 2600 mg/kg (range: 1160-49,800 mg/kg, outlier sample 282,200 mg/kg), with 11.9% of the foam samples and no textile samples containing ∑FR > 1000 mg/kg. Of these samples, tris(1-chloro-2-propyl) phosphate (TCIPP) was the most frequently detected FR (55%), followed by TDCIPP (30%) and Firemaster (FM 550, 15%). No PBDEs were detected in the post-regulatory intervention products. Our initial work on children's products showed 15% of the samples contained ∑FR > 1000 mg/kg. In our post- AB 2998 work, no regulated children's product components failed compliance (i.e., ∑FR > 1000 mg/kg). The data confirm successful adoption of the new regulations with most samples in compliance, demonstrating the efficacy of regulatory intervention. Given these results, environmental FR exposure is expected to decrease as older FR treated consumer products are replaced with FR free products.

Mercury intoxication disrupts tonic signaling in B cells, and may promote autoimmunity due to abnormal phosphorylation of STIM-1 and other autoimmunity risk associated phosphoproteins involved in BCR signaling.

Epidemiological studies link exposure to mercury with autoimmune disease. Unfortunately, in spite of considerable effort, no generally accepted mechanistic understanding of how mercury functions with respect to the etiology of autoimmune disease is currently available. Nevertheless, autoimmune disease often arises because of defective B cell signaling. Because B cell signaling is dependent on phosphorylation cascades, in this report, we have focused on how mercury intoxication alters phosphorylation of B cell proteins in antigen-non stimulated (tonic) mouse (BALB/c) splenic B cells. Specifically, we utilized mass spectrometric techniques to conduct a comprehensive unbiased global analysis of the effect of inorganic mercury (Hg2+) on the entire B cell phosphoproteome. We found that the effects were pleotropic in the sense that large numbers of pathways were impacted. However, confirming our earlier work, we found that the B cell signaling pathway stood out from the rest, in that phosphoproteins which had sites which were affected by Hg2+, exhibited a much higher degree of connectivity, than components of other pathways. Further analysis showed that many of these BCR pathway proteins had been previously linked to autoimmune disease. Finally, dose response analysis of these BCR pathway proteins showed STIM1_S575, and NFAT2_S259 are the two most Hg2+ sensitive of these sites. Because STIM1_S575 controls the ability of STIM1 to regulate internal Ca2+, we speculate that STIM1 may be the initial point of disruption, where Hg2+ interferes with B cell signaling leading to systemic autoimmunity, with the molecular effects pleiotropically propagated throughout the cell by virtue of Ca2+ dysregulation.

Monitoring Pulse Rate in the Background Using Front Facing Cameras of Mobile Devices.

We propose a novel framework to passively monitor pulse rate during the time spent by users on their personal mobile devices. Our framework is based on passively capturing the user's pulse signal using the front-facing camera. Signal capture is performed in the background, while the user is interacting with the device as he/she normally would, e.g., watch movies, read emails, text, and play games. The framework does not require subject participation with the monitoring procedure, thereby addressing the well-known problem of low adherence with such procedures. We investigate various techniques to suppress the impact of spontaneous user motion and fluctuations in ambient light conditions expected in non-participatory environments. Techniques include traditional signal processing, machine learning classifiers, and deep learning methods. Our performance evaluation is based on a clinical study encompassing 113 patients with a history of atrial fibrillation (Afib) who are passively monitored at home using a tablet for a period of two weeks. Our results show that the proposed framework accurately monitors pulse rate, thereby providing a gateway for long-term monitoring without relying on subject participation or the use of a dedicated wearable device.

CRISPR-Cas12a nucleases function with structurally engineered crRNAs: SynThetic trAcrRNA.

CRISPR-Cas12a systems are becoming an attractive genome editing tool for cell engineering due to their broader editing capabilities compared to CRISPR-Cas9 counterparts. As opposed to Cas9, the Cas12a endonucleases are characterized by a lack of trans-activating crRNA (tracrRNA), which reduces the complexity of the editing system and simultaneously makes CRISPR RNA (crRNA) engineering a promising approach toward further improving and modulating editing activity of the CRISPR-Cas12a systems. Here, we design and validate sixteen types of structurally engineered Cas12a crRNAs targeting various immunologically relevant loci in-vitro and in-cellulo. We show that all our structural modifications in the loop region, ranging from engineered breaks (STAR-crRNAs) to large gaps (Gap-crRNAs), as well as nucleotide substitutions, enable gene-cutting in the presence of various Cas12a nucleases. Moreover, we observe similar insertion rates of short HDR templates using the engineered crRNAs compared to the wild-type crRNAs, further demonstrating that the introduced modifications in the loop region led to comparable genome editing efficiencies. In conclusion, we show that Cas12a nucleases can broadly utilize structurally engineered crRNAs with breaks or gaps in the otherwise highly-conserved loop region, which could further facilitate a wide range of genome editing applications.

Comment on 'Quantum correlations are weaved by the spinors of the Euclidean primitives'.

I point out fundamental mathematical errors in the recent paper published in this journal 'Quantum correlations are weaved by the spinors of the Euclidean primitives' by Joy Christian.

Assessment of facial video-based detection of atrial fibrillation across human complexion.

Background: Early self-detection of atrial fibrillation (AF) can help delay and/or prevent significant associated complications, including embolic stroke and heart failure. We developed a facial video technology, videoplethysmography (VPG), to detect AF based on the analysis of facial pulsatile signals. Objective: The purpose of this study was to evaluate the accuracy of a video-based technology to detect AF on a smartphone and to test the performance of the technology in AF patients across the whole spectrum of skin complexion and under various recording conditions. Methods: The performance of video-based monitoring depends on a set of factors such as the angle and the distance between the camera and the patient's face, the strength of illumination, and the patient's skin tone. We conducted a clinical study involving 60 subjects with a confirmed diagnosis of AF. A continuous electrocardiogram was used as the gold standard for cardiac rhythm annotation. The VPG technology was fine-tuned on a smartphone for the first 15 subjects. Validation recordings were then done using 7053 measurements collected from the remaining 45 subjects. Results: The VPG technology detected the presence of AF using the video camera from a common smartphone with sensitivity and specificity ≥90%. The ambient level of illumination needs to be ≥100 lux for the technology to deliver consistent performance across all skin tones. Conclusion: We demonstrated that facial video-based detection of AF provides accurate outpatient cardiac monitoring including high pulse rate accuracy and medical-grade performance for AF detection.

Calculating LRs for presence of body fluids from mRNA assay data in mixtures.

Messenger RNA (mRNA) profiling can identify body fluids present in a stain, yielding information on what activities could have taken place at a crime scene. To account for uncertainty in such identifications, recent work has focused on devising statistical models to allow for probabilistic statements on the presence of body fluids. A major hurdle for practical adoption is that evidentiary stains are likely to contain more than one body fluid and current models are ill-suited to analyse such mixtures. Here, we construct a likelihood ratio (LR) system that can handle mixtures, considering the hypotheses H1: the sample contains at least one of the body fluids of interest (and possibly other body fluids); H2: the sample contains none of the body fluids of interest (but possibly other body fluids). Thus, the LR-system outputs an LR-value for any combination of mRNA profile and set of body fluids of interest that are given as input. The calculation is based on an augmented dataset obtained by in silico mixing of real single body fluid mRNA profiles. These digital mixtures are used to construct a probabilistic classification method (a 'multi-label classifier'). The probabilities produced are subsequently used to calculate an LR, via calibration. We test a range of different classification methods from the field of machine learning, ways to preprocess the data and multi-label strategies for their performance on in silico mixed test data. Furthermore, we study their robustness to different assumptions on background levels of the body fluids. We find logistic regression works as well as more flexible classifiers, but shows higher robustness and better explainability. We test the system's performance on lab-generated mixture samples, and discuss practical usage in case work.

The incidence and effect of resternotomy following cardiac surgery on morbidity and mortality: a 1-year national audit on behalf of the Association of Cardiothoracic Anaesthesia and Critical Care.

Over 30,000 adult cardiac operations are carried out in the UK annually. A small number of these patients need to return to theatre in the first few days after the initial surgery, but the exact proportion is unknown. The majority of these resternotomies are for bleeding or cardiac tamponade. The Association of Cardiothoracic Anaesthesia and Critical Care carried out a 1-year national audit of resternotomy in 2018. Twenty-three of the 35 centres that were eligible participated. The overall resternotomy rate (95%CI) within the period of admission for the initial operation in these centres was 3.6% (3.37-3.85). The rate varied between centres from 0.69% to 7.6%. Of the 849 patients who required resternotomy, 127 subsequently died, giving a mortality rate (95%CI) of 15.0% (12.7-17.5). In patients who underwent resternotomy, the median (IQR [range]) length of stay on ICU was 5 (2-10 [0-335]) days, and time to tracheal extubation was 20 (12-48 [0-2880]) hours. A total of 89.3% of patients who underwent resternotomy were transfused red cells, with a median (IQR [range]) of 4 (2-7 [1-1144]) units of red blood cells. The rate (95%CI) of needing renal replacement therapy was 23.4% (20.6-26.5). This UK-wide audit has demonstrated that resternotomy after cardiac surgery is associated with prolonged intensive care stay, high rates of blood transfusion, renal replacement therapy and very high mortality. Further research into this area is required to try to improve patient care and outcomes in patients who require resternotomy in the first 24 h after cardiac surgery.

Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial).

There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg-1 based on factor IX) or fresh frozen plasma (15 ml.kg-1 ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α2 -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.

Comparative metabolomic responses of low- and high-cadmium accumulating genotypes reveal the cadmium adaptive mechanism in Brassica napus.

Recently, oilseed rape has gathered interest for its ability to withstand elevated metal contents in plant, a key feature for remediation of contaminated soils. In this study, comparative and functional metabolomic analyses using liquid chromatography/mass spectrometry were undertaken to explore the metabolic basis of this attribute under cadmium (Cd) stress. Results revealed both conserved and differential metabolomic responses between genotype CB671 (tolerant Cd-accumulating) and its sensitive counterpart ZD622. CB671 responded to Cd stress by rearranging carbon flux towards production of compatible solutes, sugar storage forms and ascorbate, as well as jasmonates, ethylene and vitamin B6. Intriguingly, IAA abundance was reduced by 1.91-fold, which was in connection with tryptophan funnelling into serotonin (3.48-fold rise). In ZD622 by contrast, Cd provoked drastic depletion of carbohydrates and vitamins, but subtle hormones alteration. A striking accumulation of unsaturated fatty acids and oxylipins in CB671, paralleled by glycerophospholipids build-up and induction of inositol-derived signalling metabolites (up to 5.41-fold) suggested ability for prompt triggering of detoxifying mechanisms. Concomitantly, phytosteroids, monoterpenes and carotenoids were induced, denoting fine-tuned mechanisms for membrane maintenance, which was not evident in ZD622. Further, ZD622 markedly accumulated phenolics from upstream sub-classes of flavonoids; in CB671 however, a distinct phenolic wiring was activated, prioritizing anthocyanins and lignans instead. Along with cell wall (CW) saccharides, the activation of lignans evoked CW priming in CB671. Current results have demonstrated existence of notable metabolomic-based strategies for Cd tolerance in metal-accumulating oilseed rapes, and provided a holistic view of metabolites potentially contributing to Cd tolerance in this species.

Massive Tibial Bone Regeneration with Autologous Peripheral Blood Stem Cells using Ilizarov Bone Transport: A Case Report.

This is a case report of a Gustilo-Anderson Type IIIB comminuted open right tibial fracture with massive bone loss, complicated by methicillin-resistant Staphylococus aureus (MRSA) infection. Non-viable and contaminated bony fragments were removed and infected bone resected. Soft tissue coverage and antibiotics were effective against the MRSA infection. A unifocal bone transport with the Ilizarov method regenerated 13cm of the missing tibia. Autologous peripheral blood stem cells (PBSC) injections into the osteogenesis site boosted bone regeneration and consolidation with a shortened Bone Healing index (BHI) of 23 days/cm.

Complications related to peri-operative transoesophageal echocardiography - a one-year prospective national audit by the Association of Cardiothoracic Anaesthesia and Critical Care.

Previous studies on the safety of peri-operative transoesophageal echocardiography seem to suggest a low rate of associated morbidity and mortality. That said, there has been a paucity of prospective multicentre studies in this important area of clinical practice. We carried out a one-year prospective study in 2017, co-ordinated by the Association of Cardiothoracic Anaesthesia and Critical Care, to determine the rate and severity of complications associated with peri-operative transoesophageal echocardiography in anaesthetised cardiology and cardiac surgical patients. With the help of clinicians from 28 centres across the UK and Ireland, we recorded the total number of examinations conducted in anaesthetised patients during the study period. All major complications at each centre were prospectively reported and recorded. Of the 22,314 examinations, there were 17 patients diagnosed with a major complication which caused either palatal injury or gastro-oesophageal disruption. This corresponds to an incidence of 0.08% (95%CI 0.05-0.13%) or approximately 1:1300 examinations. There were seven deaths reported during the study period which were directly attributed to these complications, corresponding to an incidence of 0.03% (95%CI 0.01-0.07%) or approximately 1:3000. These figures are higher than previously reported and suggest a high probability of death following the development of a complication (~40%). Most complications occurred in patients without known risk factors for transoesophageal echocardiography associated gastro-oesophageal injury. We suggest clinicians and departments review their procedural guidelines, especially in relation to probe insertion techniques, together with the information communicated to patients when the risks and benefits of such examinations are discussed.

Dynamic Off-Body Rician Channel Modeling for Indoor Wireless Body Area Networks.

Wireless off-body channel is commonly treated as a traditional communication system assuming large and small scale fading to be independent. In this work, we challenge this approach and experimentally show that in a typical WBAN environment of a single room, this assumption is not accurate. We propose an off-body channel model where path loss and multipath fading are entirely determined by Rician distribution and linked through a stochastic Rician factor K. Treating K as a random variable, whose density is determined by the scenario under consideration, allows our model to naturally address different types of body motion along with correlated shadowing. By means of simulation supported by experiments, we show that our model is able to accurately describe probability densities of instantaneous received power in various static and dynamic settings. In addition, we demonstrate that the proposed approach can predict the off-body diversity gains due to correlated antenna reception when selection combining scheme is applied.

C-kit-derived CD11b+ cells are critical for cardiac allograft prolongation by autologous C-kit+ progenitor cells.

Autologous C-kit+ cells robustly prolong cardiac allografts. As C-kit+ cells can transdifferentiate to hematopoietic cells as well as non-hematopoietic cells, we aimed to clarify the class(es) of C-kit-derived cell(s) required for cardiac allograft prolongation. Autologous C-kit+ cells were administered post-cardiac transplantation and allografts were evaluated for C-kit+ inoculum-derived cells. Results suggested that alloimmunity was a major signal for trafficking of C-kit-derived cells to the allograft and demonstrated that C-kit+ inoculum-derived cells expressed CD11b early after transfer. Allograft survival studies with CD11b-DTR C-kit+ cells demonstrated a requirement for C-kit+-derived CD11b+ cells. Co-therapy studies demonstrated near complete abrogation of acute rejection with concomitant CTLA4-Ig therapy and no loss of prolongation in combination with Cyclosporine A. These results strongly implicate a C-kit-derived myeloid population as critical for allograft preservation and demonstrate the potential therapeutic application of autologous C-kit+ progenitor cells as calcineurin inhibitor-sparing agents and possibly as co-therapeutics for durable graft survival.

Massive Tibial Bone Regeneration with Autologous Peripheral Blood Stem Cells using Ilizarov Bone Transport: A Case Report

@#This is a case report of a Gustilo-Anderson Type IIIB comminuted open right tibial fracture with massive bone loss, complicated by methicillin-resistant Staphylococus aureus (MRSA) infection. Non-viable and contaminated bony fragments were removed and infected bone resected. Soft tissue coverage and antibiotics were effective against the MRSA infection. A unifocal bone transport with the Ilizarov method regenerated 13cm of the missing tibia. Autologous peripheral blood stem cells (PBSC) injections into the osteogenesis site boosted bone regeneration and consolidation with a shortened Bone Healing index (BHI) of 23 days/cm.

Synthetic chimeric nucleases function for efficient genome editing.

CRISPR-Cas systems have revolutionized genome editing across a broad range of biotechnological endeavors. Many CRISPR-Cas nucleases have been identified and engineered for improved capabilities. Given the modular structure of such enzymes, we hypothesized that engineering chimeric sequences would generate non-natural variants that span the kinetic parameter landscape, and thus provide for the rapid selection of nucleases fit for a particular editing system. Here, we design a chimeric Cas12a-type library with approximately 560 synthetic chimeras, and select several functional variants. We demonstrate that certain nuclease domains can be recombined across distantly related nuclease templates to produce variants that function in bacteria, yeast, and human cell lines. We further characterize selected chimeric nucleases and find that they have different protospacer adjacent motif (PAM) preferences and the M44 chimera has higher specificity relative to wild-type (WT) sequences. This demonstration opens up the possibility of generating nuclease sequences with implications across biotechnology.

Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.