Regulatory withdrawal of medicines marketed with uncertain benefits : the bevacizumab case study

Acknowledgements Professor Elizabeth Roughead is funded by a Future Fellowship from the Australian Research Council. The views expressed are those of the authors, the sponsor had no role in the preparation of the manuscript.Peer reviewedPublisher PD

Material flow analysis as a tool for environmental sanitation planning in Viet Tri, Vietnam

New environmental sanitation approaches must be developed in response to the need for more sustainable water and nutrient management. This paper illustrates how the method of Material Flow Analysis (MFA) can be applied to assess measures aiming at optimizing nitrogen recovery through improved excreta management in Viet Tri, Vietnam. The purpose of this paper is to identify how the application of MFA could be rendered more affordable for planners and decision-makers in developing countries confronted with poor data availability and quality. The analysis of the Viet Tri case indicates that a tool containing a database and assisting MFA users in determining which parameters should be determined with which accuracy (sensitivity analysis) would enable planners to optimise their data collection plan. This would help planners with limited means apply MFA as time requirement and cost for data collection would be reduced

CircleSnake: Instance Segmentation with Circle Representation

Circle representation has recently been introduced as a medical imaging optimized representation for more effective instance object detection on ball-shaped medical objects. With its superior performance on instance detection, it is appealing to extend the circle representation to instance medical object segmentation. In this work, we propose CircleSnake, a simple end-to-end circle contour deformation-based segmentation method for ball-shaped medical objects. Compared to the prevalent DeepSnake method, our contribution is three-fold: (1) We replace the complicated bounding box to octagon contour transformation with a computation-free and consistent bounding circle to circle contour adaption for segmenting ball-shaped medical objects; (2) Circle representation has fewer degrees of freedom (DoF=2) as compared with the octagon representation (DoF=8), thus yielding a more robust segmentation performance and better rotation consistency; (3) To the best of our knowledge, the proposed CircleSnake method is the first end-to-end circle representation deep segmentation pipeline method with consistent circle detection, circle contour proposal, and circular convolution. The key innovation is to integrate the circular graph convolution with circle detection into an end-to-end instance segmentation framework, enabled by the proposed simple and consistent circle contour representation. Glomeruli are used to evaluate the performance of the benchmarks. From the results, CircleSnake increases the average precision of glomerular detection from 0.559 to 0.614. The Dice score increased from 0.804 to 0.849. The code has been released: https://github.com/hrlblab/CircleSnakeComment: Machine Learning in Medical Imaging Workshop for 2022 MICCA

Identification of miRNA signatures associated with radiation-induced late lung injury in mice.

Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 70% mortality in 120 or 180 days, respectively (LD70/120 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident

Sedimentary ancient DNA: a new paleogenomic tool for reconstructing the history of marine ecosystems

Sedimentary ancient DNA (sedaDNA) offers a novel retrospective approach to reconstructing the history of marine ecosystems over geological timescales. Until now, the biological proxies used to reconstruct paleoceanographic and paleoecological conditions were limited to organisms whose remains are preserved in the fossil record. The development of ancient DNA analysis techniques substantially expands the range of studied taxa, providing a holistic overview of past biodiversity. Future development of marine sedaDNA research is expected to dramatically improve our understanding of how the marine biota responded to changing environmental conditions. However, as an emerging approach, marine sedaDNA holds many challenges, and its ability to recover reliable past biodiversity information needs to be carefully assessed. This review aims to highlight current advances in marine sedaDNA research and to discuss potential methodological pitfalls and limitations

Effect of biosynthesized silver nanoparticles on bacterial biofilm changes in S. aureus and E. coli.

One approach for solving the problem of antibiotic resistance and bacterial persistence in biofilms is treatment with metals, including silver in the form of silver nanoparticles (AgNPs). Green synthesis is an environmentally friendly method to synthesize nanoparticles with a broad spectrum of unique properties that depend on the plant extracts used. AgNPs with antibacterial and antibiofilm effects were obtained using green synthesis from plant extracts of Lagerstroemia indica (AgNPs_LI), Alstonia scholaris (AgNPs_AS), and Aglaonema multifolium (AgNPs_AM). Nanoparticles were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDX) analysis. The ability to quench free radicals and total phenolic content in solution were also evaluated. The antibacterial activity of AgNPs was studied by growth curves as well as using a diffusion test on agar medium plates to determine minimal inhibitory concentrations (MICs). The effect of AgNPs on bacterial biofilms was evaluated by crystal violet (CV) staining. Average minimum inhibitory concentrations of AgNPs_LI, AgNPs_AS, AgNPs_AM were 15 ± 5, 20 + 5, 20 + 5 μg/mL and 20 ± 5, 15 + 5, 15 + 5 μg/mL against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, respectively. The E. coli strain formed biofilms in the presence of AgNPs, a less dense biofilm than the S. aureus strain. The highest inhibitory and destructive effect on biofilms was exhibited by AgNPs prepared using an extract from L. indica

Interplay of Structural Disorder and Short Binding Elements in the Cellular Chaperone Function of Plant Dehydrin ERD14.

Details of the functional mechanisms of intrinsically disordered proteins (IDPs) in living cells is an area not frequently investigated. Here, we dissect the molecular mechanism of action of an IDP in cells by detailed structural analyses based on an in-cell nuclear magnetic resonance experiment. We show that the ID stress protein (IDSP) A. thaliana Early Response to Dehydration (ERD14) is capable of protecting E. coli cells under heat stress. The overexpression of ERD14 increases the viability of E. coli cells from 38.9% to 73.9% following heat stress (50 °C × 15 min). We also provide evidence that the protection is mainly achieved by protecting the proteome of the cells. In-cell NMR experiments performed in E. coli cells show that the protective activity is associated with a largely disordered structural state with conserved, short sequence motifs (K- and H-segments), which transiently sample helical conformations in vitro and engage in partner binding in vivo. Other regions of the protein, such as its S segment and its regions linking and flanking the binding motifs, remain unbound and disordered in the cell. Our data suggest that the cellular function of ERD14 is compatible with its residual structural disorder in vivo