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Limb girdle muscular dystrophy R12 (LGMD 2L, anoctaminopathy) mimicking idiopathic inflammatory myopathy: key points to prevent misdiagnosis
No full textObjectives: Diagnosing the idiopathic inflammatory myopathies (IIMs) can be challenging as several conditions, including genetic myopathies such as limb girdle muscular dystrophy type R12 (LGMD 2L, anoctaminopathy), mimic the presentation. Here we describe learning points identified from review of four patients with LGMD 2L who were initially incorrectly diagnosed with IIM. Our aim is to provide clinicians working in adult rheumatology services with a toolkit to help identify non-inflammatory presentations of myopathy. Methods: We performed retrospective review of medical notes, laboratory results, muscle imaging and histological findings of four patients with LGMD 2L who were previously misdiagnosed with IIM. We focused on clinical presentation and progression, therapeutic agents used, and events leading to revision of the diagnosis. Results: Three males and one female patients with a mean age of 51 years at presentation were reviewed. In each case treatment with immunosuppressants, in one case for >15 years, was observed without a clear therapeutic response. All patients were negative for anti-nuclear antibodies and available myositis-associated/specific autoantibodies and associated connective tissue disease features were absent. Prominent fatty infiltration and selective muscle involvement on thigh muscle magnetic resonance imaging was a common. Conclusions: Adult-onset genetic myopathies, particularly LGMD R12, can mimic IIM. Accurate diagnosis is crucial to avoid use of potentially harmful immunosuppressive therapies, allow appropriate genetic counselling, and facilitate involvement in research studies
Highlights from ASCO-GI 2021 from EORTC Gastrointestinal tract cancer group
No full textLast year the field of immunotherapy was finally introduced to GI oncology, with several changes in clinical practice such as advanced hepatocellular carcinoma or metastatic colorectal MSI-H. Last month, at the virtual ASCO-GI symposium 2021, several large trial results have been reported, some leading to a change of practice. Furthermore, during ASCO-GI 2021, results from early phase trials have been presented, some with potential important implications for future treatments. We provide here an overview of these important results and their integration into routine clinical practice. <br/
Arc Synthesis, Crystal Structure, and Photoelectrochemistry of Copper(I) Tungstate
No full textA little-studied p-type ternary oxide semiconductor, copper(I) tungstate (Cu2WO4), was assessed by a combined theoretical/experimental approach. A detailed computational study was performed to solve the long-standing debate on the space group of Cu2WO4, which was determined to be triclinic P1. Cu2WO4 was synthesized by a time-efficient, arc-melting method and the crystalline reddish particulate product showed broad-band absorption in the UV-visible spectral region, thermal stability up to ~260 oC,and cathodic photoelectrochemical activity. Controlled thermal oxidation of copper from the Cu(I) to Cu(II) oxidation state showed that the crystal lattice could accomodate Cu2+ cations up to ~260°C, beyond which the compound was converted to CuO and CuWO4. This process was monitored by powder X-ray diffraction and X-ray photoelectron spectroscopy. The electronic band structure of Cu2WO4 was contrasted with that of the Cu(II) counterpart, CuWO4 using spin-polarized density functional theory (DFT). Finally, the compound Cu2WO4 was determined to have a high-lying negative potential) conduction band edge underlining its promise for driving energetic photoredox reactions
The Hoarder, the Oniomaniac and the Fashionista in me::A life histories perspective on self-concept and consumption practices
No full textIncreased negative media attention has focused on the environmental impacts the fashion industry has on the natural environment, thereby calling for solutions, focused on clothing purchase, use and end-of-life treatment. This research explores the relationship between consumers and their clothing consumption (from purchase through to disposal), through the lens of life histories, and thus exploring what impacts on end-of-life clothes treatment. The novelty of this study lies within connecting fashion consumption practices with the self-concept in the context of clothing consumption (pre- purchase through to disposal), from an individual’s life history perspective. This qualitative enquiry utilised life histories, thereby conducting 20 in-depth semi-structured interviews that were analysed through a grounded approach. Findings indicate that fashion consumption is heavily influenced by an individual’s ‘self’, in that those that have a positive perception of themselves have reduced shopping habits, whilst those with a negative perception increase them. Our results show that our participants go through various consumption practices (hoarder, oniomaniac, and ‘fashionista’) that co-exist within them and are influenced by the individual’s self. Our study calls for more intergenerational studies exploring fashion consumption and disposal and the effects on the sel
Non-viral reprogramming of human nucleus pulposus cells with FOXF1 via extracellular vesicle delivery: an in-vitro and in-vivo study
No full textIntervertebral disc (IVD) degeneration is characterized by decreased cellularity, decreased proteoglycan synthesis and increased inflammation, catabolism, and neural/vascular ingrowth. Current regenerative methods for IVD degeneration are largely cell therapy based or involve viral vectors which are associated with mutagenesis and undesired immune responses. This novel study uses bulk electroporation and engineered extracellular vesicles (EVs) to deliver the transcription factor FOXF1 mRNA to degenerate human nucleus pulposus (NP) cells as a minimally invasive therapeutic strategy for regeneration of the IVD. Bulk-electroporation was used to investigate the effects of FOXF1 on human NP cells with 4-week culture in 3D agarose constructs. Engineered EV delivery of FOXF1 into human IVD cells in monolayer was determined with subsequent in-vivo validation in a pilot mouse IVD puncture model. Transfection of FOXF1 significantly altered gene expression via upregulating healthy NP markers (FOXF1, KRT19), decreasing inflammatory cytokines (IL-1β, IL6), catabolic enzymes (MMP13) and nerve growth factor (NGF) with significant increases in glycosaminoglycan accumulation in human NP cells. Engineered EVs loaded with FOXF1 demonstrated successful encapsulation of FOXF1 cargo and effective uptake by human NP cells cultured in monolayer. Injection of EVs loaded with FOXF1 into the mouse IVD in-vivo resulted in significant upregulation of FOXF1 and Brachyury compared to controls at 7-days post-injection, with no evidence of cytotoxicity. This is the first study to demonstrate non-viral delivery of FOXF1 and reprogramming of human NP cells in-vitro and mouse IVD cells in-vivo. We highlight this strategy as a non-addictive approach for treating IVD degeneration and associated back pain
Soil microbial diversity-biomass relationships are driven by soil carbon content across global biomes
No full textThe relationship between biodiversity and biomass has been a long standing debate in ecology. Soil biodiversity and biomass are essential drivers of ecosystem functions. However, unlike plant communities, little is known about how the diversity and biomass of soil microbial communities are interlinked across globally distributed biomes, and how variations in this relationship influence ecosystem function. To fill this knowledge gap, we conducted a field survey across global biomes, with contrasting vegetation and climate types. We show that soil carbon (C) content is associated to the microbial diversity-biomass relationship and ratio in soils across global biomes. This ratio provides an integrative index to identify those locations on Earth wherein diversity is much higher compared with biomass and vice versa. The soil microbial diversity-to biomass ratio peaks in arid environments with low C content, and is very low in C-rich cold environments. Our study further advances that reductions in soil C content associated with land use intensification and climate change could cause dramatic shifts in the microbial diversity-biomass ratio, with potential consequences for broad soil processes
On the Implementation of OPF Based Setpoints for Active Distribution Networks
No full textIn the context of active distribution networks, AC Optimal Power Flow (OPF) has shown great potential to calcu-late setpoints for controllable devices. Although considerable literature exists, temporal aspects that may affect the actual exe-cution of these setpoints are rarely investigated. Due to the di-verse operating characteristics of controllable devices (i.e., de-lays, ramp rates and deadbands), when these setpoints are exe-cuted by multiple devices without adequate considerations, the resulting outcome can differ drastically from what is expected; leading to violations of network constraints and excessive control actions. Therefore, this work proposes a series of necessary adap-tations within the controllers of existing devices as well as in the OPF formulation to cater for the diversity in operating charac-teristics, ensuring that calculated setpoints are adequately im-plemented by controllable devices. This involves the direct con-trol of conventional devices and enforcing a new ramping behav-ior for inverter-interfaced devices. Furthermore, a linear, mixed-integer formulation is proposed to handle discrete devices and improve scalability in large networks. Co-simulation results (us-ing a UK test network with the objective of maximizing renewa-ble energy production and considering 1s time-step) demonstrate that, by catering for the operating characteristics of controllable devices, the expected outcome from OPF-based setpoints can be achieved
Uterine remodelling bleeds into the second trimester: digitalised historic samples illuminate vascular adaptation to pregnancy
No full textTunable valley splitting and bipolar operation in graphene quantum dots
No full textQuantum states in graphene are two-fold degenerate in spins, and two-fold in valleys. Both degrees of freedom can be utilized for qubit preparations. In our bilayer graphene quantum dots, we demonstrate that the valley g-factor gv, dened analogously to the spin g-factor gs for valley splitting in perpendicular magnetic field, is tunable by over a factor of four from 20 to 90, by gate voltage adjustments only. Larger gv resultsfrom larger electronic dot sizes, determined from the charging energy. On our versatile device, bipolar operation, charging our quantum dot with charge carriers of the same or the opposite polarity as the leads, can be performed. Dots of both polarities are tunable to the first charge carrier, such that the transition from an electron to a hole dot by action of the plunger gate can be observed. Addition of gates easily extends the system to host tunable double dots
Hybrid Evolutionary-based Sparse Channel Estimation for IRS-assisted mmWave MIMO Systems
No full textThe intelligent reflecting surface (IRS)-assisted millimeter wave (mmWave) communication system has emerged as a promising technology for coverage extension and capacity enhancement. Prior works on IRS have mostly assumed perfect channel state information (CSI), which facilitates in deriving the upper-bound performance but is difficult to realize in practice due to passive elements of IRS without signal processing capabilities.In this paper, we propose a compressive channel estimation techniques for IRS-assisted mmWave multi-input and multioutput (MIMO) system. To reduce the training overhead, the inherent sparsity of mmWave channels is exploited. By utilizing the properties of Kronecker products, IRS-assisted mmWave channel is converted into a sparse signal recovery problem, which involves two competing cost function terms (measurement error and sparsity term). Existing sparse recovery algorithms solve the combined contradictory objectives function using a regularization parameter, which leads to a suboptimal solution. To address this concern, a hybrid multiobjective evolutionary paradigm is developed to solve the sparse recovery problem, which can overcome the difficulty in the choice of regularization parameter value. Simulation results show that under a wide range of simulation settings, the proposed method achieves competitive error performance compared to existing channel estimation methods