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Nickelodeon pandemonium! 3, Receiving you loud and clear
\"Calling all Nickelodeon fans! Calling all Nickelodeon fans! All-new comics featuring Nickelodeon's craziest characters are here! Join the Breadwinners, Sanjay and Craig, Harvey Beaks, Pig, Goat, Banana, Cricket, and the residents of The Loud House as they cause all sorts of Pandemonium in true Nickelodeon style!\"-- Amazon.com.
Book
The Prevalence of Asymptomatic and Symptomatic Spinal Cord Compression on Magnetic Resonance Imaging: A Systematic Review and Meta-analysis
Study Design:
Systematic review and meta-analysis.
Objectives:
Cervical spinal cord compression (SCC) due to degenerative changes of the spine is a frequent finding on magnetic resonance imaging (MRI). While most people remain asymptomatic, a proportion develop symptoms of degenerative cervical myelopathy (DCM). DCM is an often-progressive neurological disease that can cause quadriplegia. The epidemiology of SCC and DCM is poorly understood. We sought to estimate the prevalence of degenerative cervical SCC and DCM from cross-sectional cohorts undergoing MRI.
Methods:
We conducted a systematic review and meta-analysis of MRI reports on human subjects older than 16 years with degenerative SCC. A predetermined search strategy was used to identify relevant literature on MEDLINE. Title and abstract screenings were followed by full text screening. Data was extracted and analyzed by fixed or random-effects models.
Results:
The present search returned 1506 publications. Following our exclusion criteria, 19 studies were included. Subgroup analysis of 3786 individuals estimated the prevalence of asymptomatic SCC in a healthy population as 24.2% with a significantly higher prevalence of SCC in older populations compared with younger populations and American/European populations compared with Asian populations. Subgroup analysis of 1202 individuals estimated the prevalence of DCM in a healthy population as 2.3%.
Conclusions:
We present the first estimates of the prevalence of asymptomatic SCC and DCM. Studies investigating the epidemiology of SCC are heterogeneous in methodology and results. These data indicate the need for more studies into the epidemiology of SCC and DCM performed with consistent methodologies.
Journal Article
Imaging in metastatic breast cancer, CT, PET/CT, MRI, WB-DWI, CCA: review and new perspectives
Background
Breast cancer is the most frequent cancer in women and remains the second leading cause of death in Western countries. It represents a heterogeneous group of diseases with diverse tumoral behaviour, treatment responsiveness and prognosis. While major progress in diagnosis and treatment has resulted in a decline in breast cancer-related mortality, some patients will relapse and prognosis in this cohort of patients remains poor. Treatment is determined according to tumor subtype; primarily hormone receptor status and HER2 expression. Menopausal status and site of disease relapse are also important considerations in treatment protocols.
Main body
Staging and repeated evaluation of patients with metastatic breast cancer are central to the accurate assessment of disease extent at diagnosis and during treatment; guiding ongoing clinical management. Advances have been made in the diagnostic and therapeutic fields, particularly with new targeted therapies. In parallel, oncological imaging has evolved exponentially with the development of functional and anatomical imaging techniques. Consistent, reproducible and validated methods of assessing response to therapy is critical in effectively managing patients with metastatic breast cancer.
Conclusion
Major progress has been made in oncological imaging over the last few decades. Accurate disease assessment at diagnosis and during treatment is important in the management of metastatic breast cancer. CT (and BS if appropriate) is generally widely available, relatively cheap and sufficient in many cases. However, several additional imaging modalities are emerging and can be used as adjuncts, particularly in pregnancy or other diagnostically challenging cases. Nevertheless, no single imaging technique is without limitation. The authors have evaluated the vast array of imaging techniques – individual, combined parametric and multimodal - that are available or that are emerging in the management of metastatic breast cancer. This includes WB DW-MRI, CCA, novel PET breast cancer-epitope specific radiotracers and radiogenomics.
Journal Article
Stan Lee
A collection of comics that celebrates the career of prolific storyteller Stan Lee, Marvel Comics' primary creative leader for two decades and co-creator of numerous iconic superhero characters.
Book
Neural Network-Based Prediction of Wave Pressure Distribution on Hyperbolic Paraboloid Surfaces
Recent studies have demonstrated the potential of hyperbolic paraboloid (hypar), a doubly curved geometry, in coastal engineering applications. Predicting pressure distribution, critical for subsequent finite element analysis, on such novel three-dimensional structures require Computational Fluid Dynamics (CFD) simulations, which are computationally intensive. To address this challenge, the current study develops an artificial neural network (ANN) surrogate to predict pressure distributions on hypar free-surface breakwaters (FSBWs) under solitary wave loading. Using Smoothed Particle Hydrodynamics (SPH) as the CFD tool, simulations generate the supervised learning dataset, where inputs are the hypar warping R[sub.n], breakwater draft d[sub.r], and wave height H. The targets consist of two 30×30 pressure maps at wave arrival (hydrostatic) and peak, together with the wave rise time P(t[sub.0]), P(t[sub.peak]), Δt=t[sub.peak]−t[sub.0]. Three architectures, FNN, CNN, and DeepONet, are trained with homoscedastic uncertainty loss weighting, each at two parameter sizes (~50k and ~500k). Results for training and testing show that all models achieve low errors, with models with ~50k parameters found to be sufficient, and scaling to ~500k yields some generalization improvement. Further reducing the parameters (~5k) degrades accuracy for all models, with DeepONet proven most robust to parameter size reduction. Overall, this study introduces a novel SPH-ANN workflow for predicting wave pressures on hypar FSBWs, where inference on new samples occurs in a few milliseconds per sample, delivering orders-of-magnitude speedups relative to running new SPH simulations. This computational efficiency enables rapid design iteration and optimization of hypar FSBWs, facilitating their potential deployment in coastal defense.
Journal Article
Evidence of impaired macroautophagy in human degenerative cervical myelopathy
Degenerative cervical myelopathy (DCM) is a common progressive disease of the spinal cord which can cause tetraplegia. Despite its prevalence, few studies have investigated the pathophysiology of DCM. Macroautophagy is a cellular process which degrades intracellular contents and its disruption is thought to contribute to many neurodegenerative diseases. The present study tests the hypothesis that macroautophagy is impaired in DCM. To address this, we utilised a collection of post-mortem cervical spinal cord samples and investigated seven DCM cases and five human controls. Immunohistochemical staining was used to visualise proteins involved in autophagy. This demonstrated significantly reduced numbers of LC3 puncta in cases versus controls (p = 0.0424). Consistent with reduced autophagy, we identified large aggregates of p62 in four of seven cases and no controls. Tau was increased in two of five cases compared to controls. BCL-2 was significantly increased in cases versus controls (p = 0.0133) and may explain this reduction in autophagy. Increased BCL-2 (p = 0.0369) and p62 bodies (p = 0.055) were seen in more severe cases of DCM. This is the first evidence that autophagy is impaired in DCM; the impairment appears greater in more severe cases. Further research is necessary to investigate whether macroautophagy has potential as a therapeutic target in DCM.
Journal Article
Research priorities for young people with cancer: a UK priority setting partnership with the James Lind Alliance
ObjectivesTo conduct a UK-wide survey of young people who have experienced cancer, carers and professionals, to identify and prioritise research questions to inform decisions of research funders and support the case for research with this unique cancer population.DesignJames Lind Alliance Priority Setting Partnership.SettingUK health service and community.MethodsA steering group oversaw the initiative and partner organisations were recruited. Unanswered questions were collected in an online survey. Evidence searching verified uncertainties. An interim survey was used to rank questions prior to a final prioritisation workshop.ParticipantsYoung people aged 13–24 years with a current or previous cancer diagnosis, their families, friends, partners and professionals who work with this population.ResultsTwo hundred and ninety-two respondents submitted 855 potential questions. Following a refining process and removal of ‘out of scope’ questions, 208 unique questions remained. Systematic evidence checking identified seven answered questions and 16 were the subject of ongoing studies. The interim survey was completed by 174 participants. The top 30 questions were prioritised at a workshop attended by 25 young people, parents and multidisciplinary professionals. The top three priorities are: (1) What psychological support package improves psychological well-being, social functioning and mental health during and after treatment? (2) What interventions, including self-care, can reduce or reverse adverse short-term and long-term effects of cancer treatment? (3) What are the best strategies to improve access to clinical trials? The remaining questions reflect the complete cancer pathway: new therapies, life after cancer, support, education/employment, relapse and end-of-life care.ConclusionsWe have identified shared research priorities for young people with cancer using a rigorous, person-centred approach involving stakeholders typically not involved in setting the research agenda. The breadth of priorities suggest future research should focus on holistic and psychosocial care delivery as well as traditional drug/biology research.
Journal Article
Design and FEM Analysis of High-Torque Power Density Permanent Magnet Synchronous Motor (PMSM) for Two-Wheeler E-Vehicle Applications
Launch of electric vehicles have seen a substantial rise for the past few years in emerging economies like India. In countries like India, the growth and penetration of the electric vehicles in the Indian automotive industry specifically for the two-wheeler segments are driven by the demand surge where cost and motor metrics have a substantial deciding factor. The in-wheel hub-motor, which is the prime mover for the two wheelers, decides the comfort zone of the customer in various metrics such as efficiency, torque, speed range, charging, and hence the distance covered. This paper addresses the design formulation of achieving a high torque Permanent Magnet Synchronous Motor (PMSM) conventionally known as the hub-motor, explicitly for electric two-wheeler application. The hub-motor is aimed for the defined D and L (280 × 30 mm) of volumetric constraints to deliver the rated torque of 50 Nm at the spinning speed of 400 rpm. The hub-motor design is aimed for distance range of 108 km/charge, at the vehicle speed of 54 km/hr for the designed diametric and volumetric constraints. This will lead to a typical cost-effective e-vehicle system since the required distance range of 108 km is achievable at the defined rim size and geometry with an enhanced efficiency greater than 90%. The design is carried out by Finite Element Analysis (FEA) using the electromagnetic software MotorSolve. The results computed are analyzed and validated for the optimal loading conditions for the ambient temperature of 50°C. The results confirm the effectiveness of the proposed design formulation and methodology for achieving the high power density hub-motors for satisfying the customer’s comfort zone in establishing the performance metrics of the electromagnetic system.
Journal Article
Refractory Metastatic Colorectal Cancer: Current Challenges and Future Prospects
Despite advances, patients with metastatic colorectal cancer (mCRC) still have poor long-term survival. Identification of molecular subtypes is important to guide therapy through standard treatment pathways and holds promise for the development of new treatments. Following standard first- and second-line chemotherapy plus targeted agents, many patients retain a reasonable performance status, and thus are seeking further effective treatment to extend life and maintain symptom control. The challenge lies in selecting the most appropriate therapy in the third- and fourth-line settings, from a range of options including the relatively new oral agents TAS-102 and regorafenib, or rechallenge with previous chemotherapy or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (mAB). Beyond this, therapy consists of trials involving novel agents and new combinations of treatments with theoretical synergy and/or non-overlapping toxicity. There is a great focus on enhancing immunogenicity in mCRC, to reflect the impressive results of immunotherapy drugs in the small cohort with mismatch repair deficient (dMMR) mCRC. Rare molecular subtypes of mCRC are increasingly being identified, including Her2-positive disease, NTRK fusions and others. Clinical trials exploring the efficacy of immunomodulatory and precision agents are plentiful and will hopefully yield clinically meaningful results that can be rapidly translated into routine care. Keywords: molecular targets, genomic profiling, immunotherapy, precision medicine
Journal Article