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BACKGROUND: Patients with acute heart failure are frequently or systematically hospitalized, often because the risk of adverse events is uncertain and the options for rapid follow-up are inadequate. Whether the use of a strategy to support clinicians in making decisions about discharging or admitting patients, coupled with rapid follow-up in an outpatient clinic, would affect outcomes remains uncertain. METHODS: In a stepped-wedge, cluster-randomized trial conducted in Ontario, Canada, we randomly assigned 10 hospitals to staggered start dates for one-way crossover from the control phase (usual care) to the intervention phase, which involved the use of a point-of-care algorithm to stratify patients with acute heart failure according to the risk of death. During the intervention phase, low-risk patients were discharged early (in ≤3 days) and received standardized outpatient care, and high-risk patients were admitted to the hospital. The coprimary outcomes were a composite of death from any cause or hospitalization for cardiovascular causes within 30 days after presentation and the composite outcome within 20 months. RESULTS: A total of 5452 patients were enrolled in the trial (2972 during the control phase and 2480 during the intervention phase). Within 30 days, death from any cause or hospitalization for cardiovascular causes occurred in 301 patients (12.1%) who were enrolled during the intervention phase and in 430 patients (14.5%) who were enrolled during the control phase (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.78 to 0.99; P = 0.04). Within 20 months, the cumulative incidence of primary-outcome events was 54.4% (95% CI, 48.6 to 59.9) among patients who were enrolled during the intervention phase and 56.2% (95% CI, 54.2 to 58.1) among patients who were enrolled during the control phase (adjusted hazard ratio, 0.95; 95% CI, 0.92 to 0.99). Fewer than six deaths or hospitalizations for any cause occurred in low- or intermediate-risk patients before the first outpatient visit within 30 days after discharge. CONCLUSIONS: Among patients with acute heart failure who were seeking emergency care, the use of a hospital-based strategy to support clinical decision making and rapid follow-up led to a lower risk of the composite of death from any cause or hospitalization for cardiovascular causes within 30 days than usual care. (Funded by the Ontario SPOR Support Unit and others; COACH ClinicalTrials.gov number, NCT02674438.).
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/terapia , Hospitalização , Ontário , Alta do Paciente , Doença Aguda , Resultado do Tratamento , Tomada de Decisão Clínica , Canadá , Sistemas Automatizados de Assistência Junto ao Leito , AlgoritmosRESUMO
AIM: To evaluate a lesion detection algorithm designed to detect focal cortical dysplasia (FCD) in children undergoing stereoelectroencephalography (SEEG) as part of their presurgical evaluation for drug-resistant epilepsy. METHOD: This was a prospective, single-arm, interventional study (Idea, Development, Exploration, Assessment, and Long-Term Follow-Up phase 1/2a). After routine SEEG planning, structural magnetic resonance imaging sequences were run through an FCD lesion detection algorithm to identify putative clusters. If the top three clusters were not already sampled, up to three additional SEEG electrodes were added. The primary outcome measure was the proportion of patients who had additional electrode contacts in the SEEG-defined seizure-onset zone (SOZ). RESULTS: Twenty patients (median age 12 years, range 4-18 years) were enrolled, one of whom did not undergo SEEG. Additional electrode contacts were part of the SOZ in 1 out of 19 patients while 3 out of 19 patients had clusters that were part of the SOZ but they were already implanted. A total of 16 additional electrodes were implanted in nine patients and there were no adverse events from the additional electrodes. INTERPRETATION: We demonstrate early-stage prospective clinical validation of a machine learning lesion detection algorithm used to aid the identification of the SOZ in children undergoing SEEG. We share key lessons learnt from this evaluation and emphasize the importance of robust prospective evaluation before routine clinical adoption of such algorithms. WHAT THIS PAPER ADDS: The focal cortical dysplasia detection algorithm collocated with the seizure-onset zone (SOZ) in 4 out of 19 patients. The algorithm changed the resection boundaries in 1 of 19 patients undergoing stereoelectroencephalography for drug-resistant epilepsy. The patient with an altered resection due to the algorithm was seizure-free 1 year after resective surgery. Overall, the algorithm did not increase the proportion of patients in whom SOZ was identified.
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Epilepsia Resistente a Medicamentos , Epilepsia , Displasia Cortical Focal , Criança , Humanos , Pré-Escolar , Adolescente , Eletroencefalografia/métodos , Estudos Retrospectivos , Epilepsia/diagnóstico , Epilepsia/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , ConvulsõesRESUMO
Although glioblastoma is the commonest primary brain tumour in adults, its location in the cerebellum is extremely rare. We present thirteen cases (3 female, 10 male; median age at presentation 56 [age range 21-77]) of surgically managed, histologically confirmed, primary cerebellar glioblastoma (cGB) over a 17 year period (2005-2022). Pre-operative radiological diagnosis was challenging given cGB rarity, although MRI demonstrated ring enhancement in all cases. Surgical management included posterior fossa craniectomy and debulking in 11 cases and burr hole biopsy in two. CSF diversion was necessary in four cases. No evidence of IDH or ATRX gene mutations was found when tested. Survival ranged from 1 to 22 months after diagnosis (mean 10.9 months). We also seek to understand why glioblastoma is rare in this location and discuss potential reasons for this. We hypothesise that increasing anatomical distance from germinal regions and decreased local endogenous neural stem cell activity (which has been associated with glioblastoma) may explain why glioblastoma is rare in the cerebellum. We hereby seek to add to the limited literature on cGB as this is the largest UK cGB series to date.
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Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis-driven stimuli-responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, with multifunctional features that circumvent insufficient blood-brain barrier (BBB) trafficking and lack of GBM targeting-two major hurdles for anti-GBM therapies. NPs are dual-surface tailored with a i) brain-targeted acid-responsive Angiopep-2 moiety that triggers NP structural rearrangement within BBB endosomal vesicles, and ii) L-Histidine moiety that provides NP preferential accumulation into GBM cells post-BBB crossing. In tumor invasive margin patient cells, the stimuli-responsive multifunctional NPs target GBM cells, enhance cell uptake by 12-fold, and induce three times higher cytotoxicity in 2D and 3D cell models. Moreover, the in vitro BBB permeability is increased by threefold. A biodistribution in vivo trial confirms a threefold enhancement of NP accumulation into the brain. Last, the in vivo antitumor efficacy is validated in GBM orthotopic models following intratumoral and intravenous administration. Median survival and number of long-term survivors are increased by 50%. Altogether, a preclinical proof of concept supports these stimuli-responsive multifunctional NPs as an effective anti-GBM multistage chemotherapeutic strategy, with ability to respond to multiple fronts of the GBM microenvironment.
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Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Nanomedicina , Distribuição Tecidual , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Encéfalo , Barreira Hematoencefálica/patologia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Decomposition and fire are major carbon pathways in many ecosystems, yet potential linkages between these processes are poorly understood. We test whether variability in decomposability and flammability across species are related to each other and to key plant functional traits in tropical swamp forests, where habitat degradation is elevating decomposition and fire regimes. Using senesced and fresh leaves of 22 swamp tree species in Singapore, we conducted an in situ decomposition experiment and a laboratory flammability experiment. We analysed 16 leaf physical and biochemical traits as predictors of decomposability and components of flammability: combustibility, ignitability and sustainability. Decomposability and flammability were largely decoupled across species, despite some shared predictive traits such as specific leaf area (SLA). Physical traits predicted that thicker leaves with a smaller SLA and volume decomposed faster, while various cation concentrations predicted flammability components, particularly ignitability. We show that flammability and decomposability of swamp forest leaves are decoupled because flammability is mostly driven by biochemical traits, while decomposition is driven by physical traits. Our approach identifies species that are slow to decompose and burn (e.g. Calophyllum tetrapterum and Xanthophyllum flavescens), which could be planted to mitigate carbon losses in tropical swamp reforestation.
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Ecossistema , Áreas Alagadas , Florestas , Árvores/metabolismo , Plantas , Folhas de Planta/metabolismo , Carbono/metabolismoRESUMO
Differential scanning calorimetry (DSC) was used to study the fast aging behavior of two petroleum pitch materials despite being only three to five years old. We observe that these highly aromatic pitches with broad distributions of both molecular weight and aromaticity exhibit large enthalpic relaxation endotherms in initial DSC heating scans, and 20-32 °C reductions in the fictive temperature and 0.35-0.87 of θK, which are indicative of aged glasses similar to ultrastable glasses and 20 MA aged amber. Quantifying the degree of thermodynamic stability relative to the Kauzmann temperature vs. the aging time demonstrates that these materials age just as quickly as low fragility metallic glasses. Additionally, we observe that pitches age faster than polymers reported in the literature when compared using down-jump experiments. We hypothesize that the fraction of higher aromaticity of pitch molecules plays a crucial role in faster dynamics. The unique aging behavior and the ability to produce pitches in bulk quantities using pilot-scale equipment, while being possible to tailor their molecular composition, make them a useful material for studying complex aging dynamics in the deep glassy state.
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OBJECTIVE: Self-limiting Rolandic epilepsy (RE) is the most common epilepsy in school-age children. Seizures are generally infrequent, but cognitive, language, and motor coordination problems can significantly impact the child's life. To better understand brain structure and function changes in RE, we longitudinally assessed neurocognition, cortical thickness, and subcortical volumes. METHODS: At baseline, we recruited 30 participants diagnosed with RE and 24-healthy controls and followed up for 4.94 ± 0.8 years when the participants with RE were in seizure remission. Measures included were as follows: T1-weighted magnetic resonance brain imaging (MRI) with FreeSurfer analysis and detailed neuropsychological assessments. MRI and neuropsychological data were compared between baseline and follow-up in seizure remission. RESULTS: Longitudinal MRI revealed excess cortical thinning in the left-orbitofrontal (p = 0.0001) and pre-central gyrus (p = 0.044). There is a significant association (p = 0.003) between a reduction in cortical thickness in the left-orbitofrontal cluster and improved processing of filtered words. Longitudinal neuropsychology revealed significant improvements in the symptoms of developmental coordination disorder (DCD, p = 0.005) in seizure remission. CONCLUSIONS: There is evidence for altered development of neocortical regions between active seizure state and seizure remission in RE within two clusters maximal in the left-orbitofrontal and pre-central gyrus. There is significant evidence for improvement in motor coordination between active seizures and seizure remission and suggestive evidence for a decline in fluid intelligence and gains in auditory processing.
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Epilepsia Rolândica , Criança , Humanos , Epilepsia Rolândica/diagnóstico por imagem , Estudos Prospectivos , Estudos Longitudinais , Convulsões/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
We investigated how the biodistribution of cannabidiol (CBD) within the central nervous system (CNS) is influenced by two different formulations, an oil-in-water (O/W) nanoemulsion and polymer-coated nanoparticles (PCNPs). We observed that both CBD formulations administered were preferentially retained in the spinal cord, with high concentrations reaching the brain within 10 min of administration. The CBD nanoemulsion reached Cmax in the brain at 210 ng/g within 120 min (Tmax), whereas the CBD PCNPs had a Cmax of 94 ng/g at 30 min (Tmax), indicating that rapid brain delivery can be achieved through the use of PCNPs. Moreover, the AUC0-4h of CBD in the brain was increased 3.7-fold through the delivery of the nanoemulsion as opposed to the PCNPs, indicating higher retention of CBD at this site. Both formulations exhibited immediate anti-nociceptive effects in comparison to the respective blank formulations.
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Canabidiol , Nanopartículas , Humanos , Distribuição Tecidual , Dor/tratamento farmacológico , Encéfalo , Administração OralRESUMO
We report a case of coil migration into the oropharynx five years after treatment of a left internal carotid pseudoaneurysm following abandoned transsphenoidal resection of a pituitary macroadenoma. Eight other cases were found on literature review, with coil migration occurring between 2 and 120 months often after a history of transsphenoidal surgery. The majority of these were treated with trimming in a day case setting. This report highlights the need for careful extended follow up when a pseudoaneurysm forms with a concurrent skull base deficit.
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Falso Aneurisma , Lesões das Artérias Carótidas , Embolização Terapêutica , Neoplasias Hipofisárias , Humanos , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Lesões das Artérias Carótidas/etiologia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Embolização Terapêutica/efeitos adversosRESUMO
Inherited optic neuropathies are rare eye diseases of optic nerve dysfunction that present in various genetic forms. Previously, mutation in three genes encoding mitochondrial proteins has been implicated in autosomal recessive forms of optic atrophy that involve progressive degeneration of optic nerve and retinal ganglion cells (RGC). Using whole exome analysis, a novel double homozygous mutation p.L81R and pR212W in malonyl CoA-acyl carrier protein transacylase (MCAT), a mitochondrial protein involved in fatty acid biosynthesis, has now been identified as responsible for an autosomal recessive optic neuropathy from a Chinese consanguineous family. MCAT is expressed in RGC that are rich in mitochondria. The disease variants lead to structurally unstable MCAT protein with significantly reduced intracellular expression. RGC-specific knockdown of Mcat in mice, lead to an attenuated retinal neurofiber layer, that resembles the phenotype of optic neuropathy. These results indicated that MCAT plays an essential role in mitochondrial function and maintenance of RGC axons, while novel MCAT p.L81R and p.R212W mutations can lead to optic neuropathy.
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Proteína de Transporte de Acila S-Maloniltransferase/genética , Genes Recessivos , Mitocôndrias/patologia , Doenças do Nervo Óptico/patologia , Nervo Óptico/patologia , Células Ganglionares da Retina/patologia , Proteína de Transporte de Acila S-Maloniltransferase/química , Proteína de Transporte de Acila S-Maloniltransferase/metabolismo , Sequência de Aminoácidos , Animais , Criança , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Mutação , Nervo Óptico/metabolismo , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/metabolismo , Linhagem , Conformação Proteica , Células Ganglionares da Retina/metabolismo , Homologia de Sequência , Sequenciamento do ExomaRESUMO
Many people with chronic hepatitis C infection don't engage in treatment. To eliminate hepatitis C and avoid health inequalities therapy must be provided to everyone. In other diseases peers with lived experience of the condition have improved care but, for hepatitis C, studies have not shown unequivocal benefit. We completed a retrospective analysis of the English National Health Service treatment registry comparing treatment networks with and without peers using Bayesian Poisson (for count outcomes) or Bayesian Binomial (for proportion outcomes) mixed effects models with time fixed effects. For each outcome, we estimated relative ratio (RR-Poisson model) or odds ratio (Odds Ratio (OR)-Binomial model) between peer and non-peer networks. We analysed 30,729 patients within 20 operational delivery networks. In networks with peers there was an increase in the number of people initiating therapy (RR 1.12 95%, credible interval 1.02-1.21) and an increase in the proportion completing therapy (OR 2.45 95%, credible interval 1.49-3.84). However, we saw no change in proportions of people using drugs who initiated therapy nor any significant change in virological response (OR 1.14 95% credible interval 0.979-1.36). We repeated the analysis looking at the impact of peers two months after they had been introduced, when they had established networks of contacts, and saw an increase in the proportion of people treated in addiction services. In treating patients with chronic hepatitis C infection the inclusion of peer supporters may increase the number of people who initiate and complete antiviral therapy.
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Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Teorema de Bayes , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Humanos , Estudos Retrospectivos , Medicina EstatalRESUMO
Synaptic plasticity processes, which underlie learning and memory formation, require RNA to be translated local to synapses. The synaptic tagging hypothesis has previously been proposed to explain how mRNAs are available at specific activated synapses. However how RNA is regulated, and which transcripts are silenced or processed as part of the tagging process is still unknown. Modification of RNA by N6-methyladenosine (m6A/m) influences the cellular fate of mRNA. Here, by advanced microscopy, we showed that m6A demethylation by the eraser protein ALKBH5 occurs at active synaptic ribosomes and at synapses during short term plasticity. We demonstrated that at activated glutamatergic post-synaptic sites, both the YTHDF1 and YTHDF3 reader and the ALKBH5 eraser proteins increase in co-localisation to m6A-modified RNAs; but only the readers showed high co-localisation to modified RNAs during late-stage plasticity. The YTHDF1 and YTHFDF3 readers also exhibited differential roles during synaptic maturation suggesting that temporal and subcellular abundance may determine specific function. m6A-sequencing of human parahippocampus brain tissue revealed distinct white and grey matter m6A methylome profiles indicating that cellular context is a fundamental factor dictating regulated pathways. However, in both neuronal and glial cell-rich tissue, m6A effector proteins are themselves modified and m6A epitranscriptional and posttranslational modification processes coregulate protein cascades. We hypothesise that the availability m6A effector protein machinery in conjunction with RNA modification, may be important in the formation of condensed synaptic nanodomain assemblies through liquid-liquid phase separation. Our findings support that m6A demethylation by ALKBH5 is an intrinsic component of the synaptic tagging hypothesis and a molecular switch which leads to alterations in the RNA methylome, synaptic dysfunction and potentially reversible disease states.
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Epigenoma , Sinapses , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Encéfalo/metabolismo , Desmetilação , Humanos , Plasticidade Neuronal/fisiologia , Sinapses/metabolismoRESUMO
This paper presents design and operation of a multi-axis optical probe for independently measuring the relative displacements of external surfaces. Displacement is measured by mechanically modulating the optical cavity formed by an internal surface and the external surfaces, each of which comprise a Fabry-Perot interferometer. Multiple sensing axes are created using a beam splitter, and these sensing axes are separated by modulating the measurement paths at different frequencies. Two probes have been fabricated and tested; the first uses a single laser source with axes monitored by shuttering; the second probe uses two source wavelengths with beam splitting achieved using dichroic mirrors. Experimental results are presented for mirrors moving independently over distances of 1 to 2 µm with displacement noise less than 10-nm rms that is higher than the noise floor of 2.8 nm for stationary mirrors. Currently, the bandwidth is limited to the modulation frequencies ranging between 200 Hz and 2.43 kHz.
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The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating electric fields (tumor treating fields-TTFields) to the patient for the treatment of primary and recurrent Glioblastoma multiforme (GBM). Various mechanisms have been proposed to explain the effects of TTFields and other electrical therapies. Here, we present the first study of genome-wide expression of electrotherapy (delivered via TTFields or Deep Brain Stimulation (DBS)) on brain tumor cell lines. The effects of electric fields were assessed through gene expression arrays and combinational effects with chemotherapies. We observed that both DBS and TTFields significantly affected brain tumor cell line viability, with DBS promoting G0-phase accumulation and TTFields promoting G2-phase accumulation. Both treatments may be used to augment the efficacy of chemotherapy in vitro. Genome-wide expression assessment demonstrated significant overlap between the different electrical treatments, suggesting novel interactions with mitochondrial functioning and promoting endoplasmic reticulum stress. We demonstrate the in vitro efficacy of electric fields against adult and pediatric high-grade brain tumors and elucidate potential mechanisms of action for future study.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Encéfalo/patologia , Proliferação de Células/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Criança , Terapia Combinada/métodos , Terapia por Estimulação Elétrica/métodos , Estresse do Retículo Endoplasmático/genética , Fase G2/genética , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Mitocôndrias/genética , Fase de Repouso do Ciclo Celular/genéticaRESUMO
Observational studies with long-term follow-up of patients with primary central nervous system lymphoma (PCNSL) are scarce. Patient data over a period of four decades were retrospectively analysed from databases at Nottingham University Hospitals Trust, UK. The cohort was delineated by two distinct therapeutic eras; the first from 01/01/1982 to 31/12/2010 (n = 147) and the second 01/01/2011 to 31/07/2020 (n = 125). The median age at diagnosis was significantly older in the second era compared to the first (69 and 65 years respectively, P = 0·003). The 3-, 6- and 12-month overall survival (OS) rates in the second era were significantly higher compared to the first, at 85%, 77%, 62% versus 56%, 49%, 38% respectively (log-rank test P < 0·0001). On multivariate analysis, high-dose methotrexate (HD-MTX)-based induction protocols employed in the second era were associated with improved OS compared to those used in the first [hazard ratio (HR) 0·40, 95% confidence interval (CI) 0·28-0·57]. Within the second era, superior OS rates were seen with the use of intensive HD-MTX protocols (including consolidation with high-dose chemotherapy and autologous stem cell transplantation) compared to non-intensive HD-MTX schedules (HR 0·47, 95% CI 0·22-0·99). Initiating chemotherapy within 14 days of biopsy and use of rituximab were independently associated with improved OS and progression-free survival during the second era. These data suggest that prompt treatment initiation and use of intensive HD-MTX- and rituximab-based protocols have resulted in improved survival outcomes for patients.
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Neoplasias do Sistema Nervoso Central/mortalidade , Linfoma não Hodgkin/mortalidade , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carmustina/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/terapia , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Transplante de Células-Tronco Hematopoéticas , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/terapia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Mortalidade/tendências , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Reino Unido/epidemiologia , Vincristina/administração & dosagemRESUMO
A model for calculating the X-ray reflectivity (XRR) of surfaces to extract both roughness and waviness features is presented. Expressions of reflectivity intensity are derived as a function of root-mean-square (RMS) roughness σ, RMS waviness σL, and the cut-off frequency between the features ω0. Experiments were conducted at the Advanced Light Source at Lawrence Berkeley National Laboratory, beamline 8.3.2, on BK7 glass manufactured with a multi-step polishing process to validate the model, and were compared with atomic force microscopy (AFM), Fizeau interferometry and surface profilometry measurements. The parameter results and their deviations for XRR measurements were σ = 2.9 ± 0.2â nm and σL = 14.6 ± 0.5â nm with a wavelength cut-off of 1/(18â ±â 2)â µm-1, while the results from the AFM, Fizeau and profilometry measurements were σAFM = 3.4 ± 0.4â nm, σL,Fizeau = 21.6â nm, σprof = 4.0 ± 0.1â nm, and σL,prof = 21.4 ± 0.1â nm with cut-offs for the profilometry and Fizeau measurements limited to frequencies of (1/16)â µm-1 to (1/4)â mm-1.
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Pitch-based carbon fibers are of considerable interest as high-performance materials. There are reports over the last several decades detailing (i) methods of improving pitch-based carbon fiber performance, and (ii) reducing the cost of production via novel processing techniques. However, there remain considerable challenges in producing high-performance pitch-based carbon fibers consistently on an industrial scale. This is arguably due to the difficulty of scaling the melt-spinning process to compensate for variability in pitch feedstock quality and a lack of understanding of processing-structure-performance relationships. This work focuses on the early stages of heat treatment (pyrolysis) of isotropic pitch and its effect on the chemical, thermal, and rheological properties of the pitch, which help determine its processability. More specifically, we quantify significant changes in chemical structure, Mw, Tg, Ts, and shear and extensional rheology as a function of pyrolysis time at 400 °C. The extensional rheology, in particular, shows that the 'stretchability' of the pitch samples strongly depends on pyrolysis severity, and is important for characterizing 'drawability'. Using a novel analysis of the uniaxial stretching kinematics, we show an isothermal 'drawability window' that allows for the largest axial and radial Hencky strains at constant rate. We hypothesize that this extensional drawability window could facilitate the successful processing of pitch into high quality fiber, minimizing the trial-and-error approach currently used in the field.
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Quantitative markers extracted from resting-state electroencephalogram (EEG) reveal subtle neurophysiological dynamics which may provide useful information to support the diagnosis of seizure disorders. We performed a systematic review to summarize evidence on markers extracted from interictal, visually normal resting-state EEG in adults with idiopathic epilepsy or psychogenic nonepileptic seizures (PNES). Studies were selected from 5 databases and evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. 26 studies were identified, 19 focusing on people with epilepsy, 6 on people with PNES, and one comparing epilepsy and PNES directly. Results suggest that oscillations along the theta frequency (4-8â¯Hz) may have a relevant role in idiopathic epilepsy, whereas in PNES there was no evident trend. However, studies were subject to a number of methodological limitations potentially introducing bias. There was often a lack of appropriate reporting and high heterogeneity. Results were not appropriate for quantitative synthesis. We identify and discuss the challenges that must be addressed for valid resting-state EEG markers of epilepsy and PNES to be developed.
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Epilepsia , Transtornos Mentais , Adulto , Eletroencefalografia , Epilepsia/diagnóstico , Humanos , Convulsões/diagnósticoRESUMO
BACKGROUND: There is a pressing need for more sustainable healthcare. UK medical graduates are required to apply social, economic, and environmental principles of sustainability to their practice. The Centre for Sustainable Healthcare has developed a sustainability in quality improvement (SusQI) framework and educator's toolkit to address these challenges. We aimed to develop and evaluate SusQI teaching using this toolkit at Bristol Medical School. METHODS: We facilitated a SusQI workshop for all third-year Bristol Medical School students. We used mixed methods including questionnaires, exit interviews and follow-up focus groups to evaluate the outcomes and processes of learning. RESULTS: Students reported: improvements in knowledge, confidence, and attitudes in both sustainable healthcare and quality improvement; increased self-rated likelihood to engage in SusQI projects; and willingness to change practices to reduce environmental impact in their healthcare roles. Factors for successful teaching included: interactivity; collaboration and participation; and real-life, relevant and tangible examples of projects delivered by credible role models. CONCLUSIONS: Students reported that SusQI education supported by the toolkit was effective at building knowledge and skills, and reframed their thinking on sustainability in quality improvement. Combining the two topics provided enhanced motivation for and engagement in both. Further research is needed on the clinical impacts of SusQI learning.
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Educação de Graduação em Medicina , Estudantes de Medicina , Currículo , Humanos , Aprendizagem , Melhoria de Qualidade , Faculdades de MedicinaRESUMO
BACKGROUND: The healthcare sector is a major contributor to climate change and there are international calls to mitigate environmental degradation through more sustainable forms of clinical care. The UK healthcare sector has committed to net zero carbon by 2040 and sustainable healthcare is a nationally mandated outcome for all UK graduating doctors who must demonstrate their ability to address social, economic, and environmental challenges. Bristol Medical School piloted successful Sustainability in Quality Improvement (SusQI) workshop, but identified challenges translating classroom learning into clinical practice. This paper aims to identify and address those challenges. METHODS: We conducted five focus groups that identified and iteratively explored barriers and facilitators to practice among medical students, comparing a range of experiences to generate a conceptual model. We then combined our findings with behaviour change theory to generate educational recommendations. RESULTS: Students that applied their learning to the clinical workplace were internally motivated and self-determined but needed time and opportunity to complete projects. Other students were cautious of disrupting established hierarchies and practices or frustrated by institutional inertia. These barriers impacted on their confidence in suggesting or achieving change. A minority saw sustainable healthcare as beyond their professional role. CONCLUSIONS: We present a series of theoretically informed recommendations. These include wider curricular engagement with concepts of sustainable clinical practice; supportive workplace enablement strategies such as workplace champions and co-creation of improvement goals; and time and headspace for students to engage through structured opportunities for credit-bearing project work.