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Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

Abstract Background Osteonecrosis of the femoral head can be a debilitating disease leading to collapse of the femoral head and the subsequent need for a hip arthroplasty. Core decompression has emerged as a leading treatment to prevent collapse. Adjunctive therapies, such as bone graft, bone marrow aspirate concentrates, or synthetic bone substitutes are utilized to promote native bone regeneration. Determining the amount of bone resected and the volume of adjunct required is challenging, especially with newer minimally invasive reamers. Under- or over-filling the defect may impact progression of the disease or cause morbidity. Surgical technique We introduce a mathematical method to be utilized intraoperatively to calculate the volume of bone resected during core decompression with an expandable reamer. This method approximates the core decompression defect as two cylinders using measurements that can be easily taken during the procedure and can be adapted for use with any of the expandable reamer systems available. Using this technique, surgeons can calculate the size of the defect created, which can be used to personalize the amount of adjunct delivered to each patient. Conclusions When adjunctive therapies are used with core decompression to treat ONFH, care must be taken when filling the core decompression defect to avoid under- or over-filling the defect, potentially increasing the risk of complications or reducing the efficacy of the procedure. We provide a simple worksheet that can be used by surgeons to help determine how much adjunct should be used.

Abstract Linear and volumetric analysis are the typical methods to measure tumor size. 3D volumetric analysis has risen in popularity; however, this is very time and labor intensive limiting its implementation in clinical practice. This study aims to show that an AI-led approach can shorten the length of time required to conduct 3D volumetric analysis of VS tumors and improve image processing accuracy. From Yale New Haven Hospital and public patient recruitment, 143 MRIs were included in the ground truth dataset. To create the tumor models for the ground truth dataset, an image processing software (Simpleware ScanIP, Synopsys) was used. The helper (DPP V1.0) was trained using proprietary AI- and ML-based algorithms and information. A proof-of-concept AI model achieved a mean DICE score of 0.76 (standard deviation 0.21). After the final testing stage, the model improved to a final mean DICE score of 0.88 (range 0.74–0.93, standard deviation 0.04). Our study has demonstrated an efficient, accurate AI for 3D volumetric analysis of vestibular schwannomas. The use of this AI will enable faster 3D volumetric analysis compared to manual segmentation. Additionally, the overlay function would allow visualization of growth patterns. The tool will be a method of assessing tumor growth and allow clinicians to make more informed decisions.

Abstract We introduce a family of membrane-targeted azobenzenes (MTs) with a push-pull character as a new tool for cell stimulation. These molecules are water soluble and spontaneously partition in the cell membrane. Upon light irradiation, they isomerize from trans to cis, changing the local charge distribution and thus stimulating the cell response. Specifically, MTs photoisomerization induces clear and reproducible depolarization. The most promising species, MTP2, was extensively studied. Time-resolved spectroscopy techniques provide insights into the excited state evolution and a complete understanding of its isomerization reaction. Molecular Dynamics simulations reveal the spontaneous and stable partitioning of the compound into the cellular membrane, without significant alterations to the bilayer thickness. MTP2 was tested in different cell types, including HEK293T cells, primary neurons, and cardiomyocytes, and a steady depolarization is always recorded. The observed membrane potential modulation in in-vitro models is attributed to the variation in membrane surface charge, resulting from the light-driven modulation of the MT dipole moment within the cell membrane. Additionally, a developed mathematical model successfully captures the temporal evolution of the membrane potential upon photostimulation. Despite being insufficient for triggering action potentials, the rapid light-induced depolarization holds potential applications, particularly in cardiac electrophysiology. Low-intensity optical stimulation with these modulators could influence cardiac electrical activity, demonstrating potential efficacy in destabilizing and terminating cardiac arrhythmias. We anticipate the MTs approach to find applications in neuroscience, biomedicine, and biophotonics, providing a tool for modulating cell physiology without genetic interventions.

Abstract Background informal caregivers of people with dementia are at greater risk of developing physical and mental health problems when compared to the general population: they often experience high levels of stress which can lead to a lowered sense of well-being, feelings of being burdened, depression and compromised physical health. The significant beneficial effects of Psychoeducational Interventions on the critical outcomes of caregiver burden and strain were considered sufficient to warrant a recommendation in favour of the intervention. The emergence of the COVID-19 pandemic has significantly increased the use internet-based interventions: this study describes the effectiveness of support program for informal caregivers of people with dementia internet-based and on-site conditions. Methods A Psychoeducational Interventions program, consisting of 5 meetings every 2 weeks, has been structured. It aims to provide information and strategies for managing cognitive and psycho-behavioral symptoms in neurodegenerative diseases, as well as to develop effective communication skills and understanding of the caregiver's experience. Intervention formats include slides, video, group discussions and are always led by a psychologist. We assessed in 73 caregivers (33 internet-based and 40 on-site conditions) level of Behavioural and Psychological Symptoms of Dementia management, dementia awareness, social support, find leisure time, harmony with relative, stress, with Visual-Analogue Scale at the beginning of PI and at the end. During the pandemic period the protocol was adapted to be available online and subsequently proposed to caregivers belonging to the Cognitive Disorders and Dementia Centre. Results in both modalities, internet-based and on-site condition, a statistically significant improvement was highlighted in all aspects (p

The development of anticancer diagnostic and therapeutic strategies is of crucial importance to improve efficacy and therapeutic specificity. Here, we describe the synthesis and characterization of fluorescent self-assembling nanomicelles (NMs) based on a biocompatible polysaccharide (cellulose, CE) functionalized with a tetraphenyl ethylene derivative (TPEHy) and loaded with Doxorubicin (DOX) with aggregation-induced emission (AIE) properties and pH-dependent drug release. We obtained CE-TPEHy-NMs with an average diameter of 60 ± 17 nm for unloaded NMs and 86 ± 25 nm for NMs loaded with DOX, respectively. Upon testing different conditions, we obtained an encapsulation efficiency of 86% and a loading capacity of 90%. A controlled dialysis experiment showed that the release of DOX after 48 h is minimal at pH 7.4 (11%), increasing at pH 6.5 (50%) and at its maximum at pH 4.5 (80%). The cytotoxicity of blank and loaded CE-TPEHy-NMs at increasing concentrations and different pH conditions was tested on a MG-63 human osteosarcoma cell line. Based on viability assays at pH 7.4, neither unloaded nor loaded CE-TPEHy-NMs exerted any inhibition on cell proliferation. At pH 6.5, proliferation inhibition significantly increased, confirming the pH-dependent release. We characterized and studied the performance of CE-based amphiphilic, biocompatible NMs for controlled drug release in acidic conditions, such as tumor microenvironments. Further studies are required to optimize their synthesis process and to validate their antitumoral properties in vivo.

Background: Multiple options exist for fulcrums in balanced cable bone segment transport (BC-BST) procedures, but there is no consensus among orthopedic surgeons on best practices. Aims and Objectives: This study investigates the mechanical differences between a variety of fulcrums used to perform this reconstructive technique. Materials and Methods: A custom testing rig was built to determine the tension-modifying effects of different fulcrums on the BC-BST system. Results: The stiffness of the system was inversely related to the displacement of the spring, and the least stiff system occurred in fulcrums without threads and of larger diameter. Conclusion: These observed differences suggest that the diameter and type of fulcrum used impact the BC-BST system and there may be an opportunity for greater personalization of the pull tension.

Purpose: To examine a method to visualize a 3-dimensional (3D) rendered distal femur using 3D curvature analysis and to compare models of patellofemoral instability (PFI) with controls to study the reliability of the entry point to trochlear groove angle (EPTG) metric. Methods: The 3D models of patients with recurrent patellar instability, defined by at least 2 reported patellar dislocation events, and age- and sex-matched controls were created from computed tomography scans. Curvature was calculated to highlight the proximal trochlear ridges and the trochlear groove by overlaying them on the 3D models. Anteroposterior views with and without curvature visualization were created and used for qualitative comparison and to measure the EPTG. The EPTG was measured by 2 raters with and without the aid of the curvature maps. Significant differences between patients with PFI and controls were compared with a Mann-Whitney U test. Inter-rater reliability was calculated using interclass correlation coefficients, classified according to literature and compared using a permutation test. Significance was assumed at .05. Results: Qualitive analysis between 30 PFI patient knees (age: 23.9 ± 8.4 years, female/male: 24/6) and 30 control knees (age: 21.8 ± 5.6 years, female/male: 22/8) showed that in general, patients with PFI have a lateralized medial ridge and trochlear groove, with the trochlear groove being shorter and shallower. Qualitatively, differences between patients with PFI and controls were significant for measurements both with and without the aid of the curvature maps. Inter-rater reliability was significantly (P = .0349) better when using the curvature visualization. Conclusions: Curvature-based visualization aids overlain on a 3D model have the power to increase the information gained from 3D imaging and corresponding 3D models, amplifying their potential value in clinical decision-making. Such visualizations facilitate both the identification of qualitative differences between patient and control morphology and improve the reliability of the EPTG trochlear dysplasia metric. Level of Evidence: Level III, retrospective cohort study.

IntroductionEvidence increasingly shows that facial emotion recognition (FER) is impaired in refractory mesial temporal lobe epilepsy (rMTLE), especially in patients with a right focus. This study explores FER in both mild (mMTLE) and refractory forms, examining the influence of epileptic focus lateralization on FER.Methods50 MTLE patients, categorized by epilepsy severity and focus lateralization, were compared with healthy controls. FER was assessed using the Ekman Faces Test (EFT), which evaluates recognition of six basic emotions, alongside a battery of cognitive and mood tests.ResultsmMTLE patients showed selective deficits in recognizing fear and anger, while rMTLE patients displayed broader deficits, affecting all emotions except surprise. Patients with a right focus underperformed across all negative emotions, whereas those with a left focus showed deficits mainly in fear and anger. Analysis indicated that early epilepsy onset was associated with poorer FER in right-focused patients; febrile seizures and mesial temporal sclerosis significantly impacted FER in left-focused patients.ConclusionMTLE affects circuits of FER even in mild subjects, although to a lesser extent than in refractory ones. Earlier onset of MTLE could disrupt the development of FER, possibly interfering during a critical phase of maturation of its circuits, when the focus is right. Conversely, left MTLE may cause less damage to FER circuits, requiring additional factors such as a history of febrile seizures and/or mesial temporal sclerosis for significant impact. Clinically, refractory and right-sided MTLE might be viewed as risk factors of FER deficits.

Abstract Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

This paper aims to develop sustainable geopolymer composites reinforced with silverskin fibers derived from coffee industry waste. Geopolymer and geopolymer composites were synthesized from blast furnace slags (BFS) with a solid/liquid (alkaline solution) ratio of 1.4. A sodium metasilicate/sodium hydroxide (Na2SiO3/NaOH) mixture at a mass ratio of 2.5 served as the alkaline activator in the geopolymerization process. The composites were evaluated by incorporating 2%, 3%, and 5% by weight of silverskin fibers, which were used in their natural form (SGCn), after treatment with sodium hydroxide (SGCNaOH), and after treatment with sodium hydroxide followed by a steam explosion process (SGCSE).Characterizations of the geopolymer composites included X-ray fluorescence analysis (XRF) for elemental oxide identification, Fourier transform infrared spectroscopy (FTIR) for functional group detection, and thermogravimetric analysis (TGA) for thermal stability assessment. The influence of fibers on the hardness of the geopolymer materials was evaluated using hardness scale measurements. Morphologies, microstructures, and elemental compositions were analyzed through field emission gun scanning electron microscopy with energy dispersive X-ray spectroscopy (FEG-SEM/EDS).The results demonstrate that the incorporation of silverskin fibers, especially those treated with NaOH and subjected to steam explosion, significantly enhances the thermal stability of geopolymer composites. The 5% NaOH-treated fiber composite exhibited the highest Tmax and Tend, indicating superior thermal stability. Additionally, the 5% SGCNaOH composite showed the highest residual mass, further supporting the enhanced thermal stability of these composites.Unlike other fibers, which showed a decrease in hardness, the addition of SGCSE fibers maintains a relatively high hardness in the geopolymer composites. The 2% SGCSE composite exhibited an average hardness equal to that of the pure geopolymer at 66 Shore D.These findings underscore the potential of using treated silverskin fibers to develop more thermally stable, cost-effective, and sustainable geopolymer materials. By utilizing industrial residues and waste, these advanced materials can be applied in the production of construction and building materials, contributing to both environmental sustainability and economic efficiency.

Climate change poses a threat not only to the environmental and physical aspects of the places where people live, but also to their identities and ways of living, as well as those of the communities around them. Conducted as part of the requirements of the Master of Advanced Studies in Marine Biodiversity and Conservation at Scripps Institution of Oceanography (SIO), this capstone project consists of a climate vulnerability assessment of the La Fortaleza and San Juan National Historic Site World Heritage Site in Puerto Rico, based on a literature review of existing scientific data. Its purpose is to inform a broader effort led by SIO’s Human Ecology Lab, which will complement this top-down approach with a bottom-up assessment of climate change threats to the area based on the perspectives of local stakeholders. This project includes two products: the full climate vulnerability assessment presented below and an online summary of its main findings with interactive maps, which can be found at https://arcg.is/1quumK. Ultimately, this project contributes to the ongoing development of a climate vulnerability assessment tool for cultural heritage that can be used independently by stakeholders to meaningfully assess the vulnerability of their own cultural heritage to climate change through a decentralized process that can inspire local climate action, inform decision-making at different levels, and be repeated consistently as the components of vulnerability change over time.  Please see the media created for this project here: https://storymaps.arcgis.com/stories/79ebff9ddfd741d788141b1b10cb0b54

Abstract The SHiP-charm project was proposed to measure the associated charm production induced by 400 GeV/c protons in a thick target, including the contribution from cascade production. An optimisation run was performed in July 2018 at CERN SPS using a hybrid setup. The high resolution of nuclear emulsions acting as vertex detector was complemented by electronic detectors for kinematic measurements and muon identification. Here we present first results on the analysis of nuclear emulsions exposed in the 2018 run, which prove the capability of reconstructing proton interaction vertices in a harsh environment, where the signal is largely dominated by secondary particles produced in hadronic and electromagnetic showers within the lead target.

Currently, problems related to antibiotic resistance are shifting the focus of pharmaceutical research towards natural molecules with antibacterial properties. Among them, flavonoids represent promising molecules with strong antibacterial features; however, they have poor biopharmaceutical properties. In this study, we developed solid lipid nanoparticles (SLNs) loaded with the flavanone naringenin (NRG) to offer an option for treating bacterial infections. NRG-SLNs systems were prepared by a solvent emulsification/diffusion and ultrasonication method, using Compritol® 888 ATO (COM) as the lipid. The optimal formulation was obtained using a 10% (w/w) theoretical amount of NRG (NRG10-SLNs), exhibiting homogeneous sizes (approximately 50 nm and 0.15 polydispersity index), negative zeta potential (−30 mV), and excellent encapsulation parameters (an encapsulation efficiency percentage of 97.9% and a drug content of 4%). NRG10-SLNs presented good physical stability over 4 weeks. A cumulative drug release of 55% in 24 h and the prolonged release of the remaining amount over 10 days was observed. In addition, µ-Raman spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction measurements were carried out to characterize the drug–lipid interactions. Finally, the in vitro antibacterial and antibiofilm activities of NRG10-SLNs were assayed and compared to free NRG. NRG10-SLNs were bacteriostatic against Staphylococcus aureus, including the methicillin-resistant S. aureus (MRSA) and Escherichia coli strains. An improvement in the antibacterial activity of NRG-loaded SLNs compared to the free molecule was observed against S. aureus strains, probably due to the interaction of the surfactant-coated SLNs with the bacterial surface. A similar trend was observed for the biofilm inhibition.