Search

Abstract Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0–36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.

Introduction: Articular cartilage injuries of the knee are a complex and challenging clinical pathology. Objectives: The purpose of this study was to establish consensus statements via a Delphi process on the management of failed knee cartilage surgery. Methods: A consensus process on knee cartilage injuries utilizing a modified Delphi technique was conducted. Seventy-nine surgeons across 17 countries participated in these consensus statements. Eleven questions were generated on the management of failed knee cartilage surgery, with 3 rounds of questionnaires and final voting occurring. Consensus was defined as achieving 80% to 89% agreement, whereas strong consensus was defined as 90% to 99% agreement, and unanimous consensus was defined as 100% agreement with a proposed statement. Results: Of the 11 total questions and consensus statements on the management of failed knee cartilage surgery developed from 3 rounds of voting, 0 achieved unanimous consensus, 10 achieved strong consensus, and 1 achieved consensus. Conclusions: The statements that achieved strong consensus related to revision cartilage indications, contraindications, lesion size, prior procedures, unipolar/bipolar lesions, and salvage procedures. The statement that did not achieve strong consensus was related to the management of a failed osteochondral autograft/allograft.

Introduction Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective.Methods and analysis The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement.Ethics and dissemination The trial was approved by the London—Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.Trial registration number ISRCTN87336549.

Objectives: Identifying the key factors associated with vaccine hesitancy remains a challenge as has been highlighted throughout the COVID-19 vaccine roll out and pandemic. The aim of this study was to determine characteristics associated with vaccine safety and compare perceived safety by vaccine. Our hypothesis is that vaccine safety perception will vary by vaccine with COVID-19 as ranked lowest for safety. Study design: Cross sectional. Methods: A statewide sample (n = 1024) responded to an online 28-point questionnaire via anonymous linked invitation. Results: Among the eight vaccines assessed, COVID-19 had the lowest perceived safety (53.13%) followed by human papillomavirus HPV (63.38%). A binomial logistic regression assessed COVID-19 vaccine safety beliefs (safe v not safe) finding age, political orientation, and perceived safety of certain vaccines as statistically significant. As age increased by year, vaccine safety beliefs increased. Persons who identified as conservative demonstrated less belief in vaccine safety than all other groups. Among persons who did not perceive the COVID-19 vaccine as safe, 65.8% believed chicken pox was safe, 63.3% and 61.1% perceived hepatitis A& B were safe. Conclusions: These findings demonstrate that vaccine safety beliefs differ by vaccine and that persons who do not believe in the safety of the COVID-19 are not exclusively against all vaccines. Understanding factors that increase vaccine safety by vaccine could assist in developing an intervention which could increase belief in safety for all vaccines.

Abstract The notion that phonons can carry pseudo‐angular momentum has many major consequences, including topologically protected phonon chirality, Berry curvature of phonon band structure, and the phonon Hall effect. When a phonon is resonantly coupled to an orbital state split by its crystal field environment, a so‐called vibronic bound state forms. Here, a vibronic bound state is observed in NaYbSe2, a quantum spin liquid candidate. In addition, field and polarization dependent Raman microscopy is used to probe an angular momentum transfer of ΔJz = ±ℏ between phonons and the crystalline electric field mediated by the vibronic bound stat. This angular momentum transfer between electronic and lattice subsystems provides new pathways for selective optical addressability of phononic angular momentum via electronic ancillary states.

Background Electronic health systems contain large amounts of unstructured data (UD) which are often unanalyzed due to the time and costs involved. Unanalyzed data creates missed opportunities to improve health outcomes. Natural language processing (NLP) is the foundation of generative artificial intelligence (GAI), which is the basis for large language models, such as ChatGPT. NLP and GAI are machine learning methods that analyze large amounts of data in a short time at minimal cost. The ability of NLP to conduct qualitative analyses is increasing, yet the results can lack context and nuance in their findings, requiring human intervention. Methods Our study compared outcomes, time, and costs of a previously published qualitative study. Our approach partnered an NLP model and a qualitative researcher (NLP+). UD from behavioral health patients were analyzed using NLP and a Latent Dirichlet allocation to identify the topics using probability of word coherence scores. The topics were then analyzed by a qualitative researcher, translated into themes, and compared with the original findings. Results The NLP + method results aligned with the original, qualitative derived themes. Our model also identified two additional themes which were not originally detected. The NLP + method required 6 hours of labor, 3 minutes for transcription, and a transcription cost of $1.17. The original, qualitative researcher only method required more than 36 hours ($2,250) of time and $1,100 for transcription. Conclusions While natural language processing analyzes voluminous amounts of data in seconds, context and nuance in human language are regularly missed. Combining a qualitative researcher with NLP + could be deployed in many settings, reducing time and costs, and improving context. Until large language models are more prevalent, a human interaction can help translate the patient experience by contextualizing data rich in social determinant indicators which may otherwise go unanalyzed.

Abstract Background Isolated ACL reconstructions (ACLR) demonstrate limitations in restoring native knee kinematics. This study investigates the knee mechanics of ACLR plus various anterolateral augmentations using a patient-specific musculoskeletal knee model. Materials and methods A patient-specific knee model was developed in OpenSim using contact surfaces and ligament details derived from MRI and CT data. The contact geometry and ligament parameters were varied until the predicted knee angles for intact and ACL-sectioned models were validated against cadaveric test data for that same specimen. Musculoskeletal models of the ACLR combined with various anterolateral augmentations were then simulated. Knee angles were compared between these reconstruction models to determine which technique best matched the intact kinematics. Also, ligament strains calculated by the validated knee model were compared to those of the OpenSim model driven by experimental data. The accuracy of the results was assessed by calculating the normalised RMS error (NRMSE); an NRMSE 60%). Similar errors were observed between ACL strain results (NRMSE > 60%). Other ligament comparisons were acceptable. All ACLR plus anterolateral augmentation models restored kinematics toward the intact state, with ACLR plus anterolateral ligament reconstruction (ACLR + ALLR) achieving the best match and the greatest strain reduction in ACL, PCL, MCL, and DMCL. Conclusion The intact and ACL-sectioned models were validated against cadaveric experimental results for all rotations. It is acknowledged that the validation criteria are very lenient; further refinement is required for improved validation. The results indicate that anterolateral augmentation moves the kinematics closer to the intact knee state; combined ACLR and ALLR provide the best outcome for this specimen.

Despite decades of research and clinical trials, metastatic castration-resistant prostate cancer (mCRPC) remains incurable and typically fatal. Current treatments may provide modest increases in progression-free survival but can come with significant adverse effects and are disaggregated from the diagnostic imaging needed to fully assess the spread of metastatic disease. A theranostic approach, using radiolabeled ligands that target the cell surface protein PSMA, simplifies the visualization and disease treatment process by enabling both to use similar agents. Here, we describe an exemplary case wherein a gentleman in his 70s with mCRPC on diagnosis was treated with 177Lu–PSMA-617 and abiraterone, and remains disease-free to date, over five years later.

Abstract Objective The primary aim of the present study was to evaluate the long-term outcomes including survivorship of computer navigated distal femoral lateral opening wedge osteotomy (DFLOWO). The secondary aim was to identify the potential factors that may influence its survivorship. Methods A retrospective analysis of prospectively collected data for patients with lateral compartment arthritis who underwent navigated DFLOWO from December 2006 to November 2012 was performed. The International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were analyzed for outcome measures. Conversion to arthroplasty during the follow-up was the end point. Results A total of 19 DFLOWOs were performed in 17 patients with a mean age of 46.6 ± 6.5 years formed the study cohort. The coronal alignment was corrected from a mean of 7.1° (2-11°) valgus to a mean of 2.1° (0.5°-3°) varus. The IKDC scores improved from mean of 39 preoperatively to 53 at the mean long-term follow-up of 9.1 years. The mean KOOS scores at the long-term follow-up were pain 71, symptoms 56, activities of daily living 82, sports and recreation 59, quality of life 43. Survivorship of the DFLOWO was 78.9% at a follow-up of 9.1 years. Presence of ≥ grade 2 according to the International Cartilage Repair Society (ICRS) cartilage degeneration in the medial compartment of the knee and >7° preoperative valgus deformity were strongly correlated with conversion to total knee arthroplasty (TKA) at the long-term follow-up (r= 0.66). ConclusionsComputer navigated DFLOWO has satisfactory clinical outcomes and 79% survivorship in long-term follow-up. Presence of more than ICRS ≥ grade 2 degenerative changes in the medial compartment of knee with > 7° preoperative valgus deformity negatively affects the survivorship of DFLOWO in the long-term follow-up.

Here, the authors introduce a live-cell imaging system using chiroptical contrast, enabling the study of chiral interactions. They demonstrate simultaneous imaging of enantiomeric pairs of molecular probes emitting circularly polarised light, using both single and two-photon excitation.

While the anatomical properties of regenerated axons across spinal cord lesion sites have been studied extensively, little is known of how the functional properties of regenerated synapses compared to those in unlesioned animals. This study aims to compare the properties of synapses made by regenerated axons with unlesioned axons using the lamprey, a model system for spinal injury research, in which functional locomotor recovery after spinal cord lesions is associated with axonal regeneration across the lesion site. Regenerated synapses below the lesion site did not differ from synapses from unlesioned axons with respect to the amplitude and duration of single excitatory postsynaptic potentials. They also showed the same activity-dependent depression over spike trains. However, regenerated synapses did differ from unlesioned synapses as the estimated number of synaptic vesicles was greater and there was evidence for increased postsynaptic quantal amplitude. For axons above the lesion site, the amplitude and duration of single synaptic inputs also did not differ significantly from unlesioned animals. However, in this case, there was evidence of a reduction in release probability and inputs facilitated rather than depressed over spike trains. Synaptic inputs from single regenerated axons below the lesion site thus do not increase in amplitude to compensate for the reduced number of descending axons after functional recovery. However, the postsynaptic input was maintained at the unlesioned level using different synaptic properties. Conversely, the facilitation from the same initial amplitude above the lesion site made the synaptic input over spike trains functionally stronger. This may help to increase propriospinal activity across the lesion site to compensate for the lesion-induced reduction in supraspinal inputs. The animal experiments were approved by the Animal Ethics Committee of Cambridge University.

Este texto fue originalmente publicado por David S. Parker en el año 1998 como introducción al libro The Idea of the Middle Class: White-Collar Workers and Peruvian Society, 1900-1950, publicado por la editorial Penn State University. En él, el autor reflexiona sobre la sindicación de los empleados de Lima (Perú) y sobre el origen de la ley de 1924 que estableció una distinción legal entre empleado y obrero. Tanto la escuela «constructivista» como el giro lingüístico plantean que las clases sociales son abstracciones, inventos del imaginario colectivo, es decir, ideas que compiten en un mercado ideológico. De entre las infinitas maneras de conceptualizar la sociedad solo unas cuantas imágenes y discursos llegan a convertirse en sentido común, influyendo en la formación de identidades e inspirando leyes y políticas públicas. El presente texto afirma y caracteriza que la formación del concepto clase media en el Perú se debe a procesos ideológicos, discursivos y políticos.