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Objectives The use of Bruton’s tyrosine kinase (BTK) inhibitors has changed the clinical history of patients with chronic lymphocytic leukemia (CLL) in both naïve and relapsed/refractory settings. “Accelerated” chronic lymphocytic leukemia (a-CLL) is a relatively rare form of CLL representing less than 1 % of all CLL cases. a-CLL patients usually have a more aggressive course and a reduced overall survival was reported with conventional chemo-immunotherapy approaches. Methods The role of Bruton Tyrosine Kinase-inhibitor, ibrutinib, in a-CLL is well established with encouraging preliminary results. Results We report a case of a-CLL-treated first-line with second-generation BTKi, acalabrutinib with a prompt clinical response. As known, it is the first literature report on acalabrutinib in a-CLL highlighting the role of second-generation BTKi also in this high-risk setting. Conclusions Target therapies (Bruton Kinase inhibitors and Bcl2 inhibitors) have improved the therapeutic landscape of CLL. The availability of therapeutic targets requires greater diagnostic accuracy to choose the most appropriate therapy for each patient.

Primary Sjögren's syndrome (pSS) is an autoimmune systemic disease mainly affecting exocrine glands and resulting in disabling symptoms, as dry eye and dry mouth. Mechanisms underlying pSS pathogenesis are intricate, involving multiplanar and, at the same time, interlinked levels, e.g., genetic predisposition, epigenetic modifications and the dysregulation of both immune system and glandular-resident cellular pathways, mainly salivary gland epithelial cells. Unravelling the biological and molecular complexity of pSS is still a great challenge but much progress has been made in recent years in basic and translational research field, allowing the identification of potential novel targets for therapy development. Despite such promising novelties, however, none therapy has been specifically approved for pSS treatment until now. In recent years, growing evidence has supported the modulation of Janus kinases (JAK) - signal transducers and activators of transcription (STAT) pathways as treatment strategy immune mediated diseases. JAK-STAT pathway plays a crucial role in autoimmunity and systemic inflammation, being involved in signal pathways of many cytokines. This review aims to report the state-of-the-art about the role of JAK-STAT pathway in pSS, with particular focus on available research and clinical data regarding the use of JAK inhibitors in pSS.

A Síndrome hemofagocitica (SHF) é um quadro caracterizado por uma proliferação maligna de histiocitos com intensa atividade fagocitaria de células saudáveis, ocasionando a ativação sistêmica de macrófagos, levando a um processo inflamatório agudo grave, rapidamente progressivo. É uma condição clínica de difícil diagnóstico e com múltiplas causas: infecções, neoplasias, doenças autoimunes e doenças onco-hematologicas. Objetivos: expor um relato de caso da SHF, atendido em um pronto atendimento de um hospital de grande centro e apresentar uma discussão a cerca dessa doença com base na literatura, considerando sua dificuldade em fazer o diagnóstico e sua gravidade. O maior empecilho para o tratamento bem sucedido é um atraso no diagnóstico e infelizmente esse fator ocorre em vista da raridade da síndrome, da apresentação clínica variável e da falta de especificidade dos achados clínicos e laboratoriais. Logo, a importância de iniciar tratamento quando houver uma suspeita clínica forte de síndrome hemofagocítica. Conclusão: vê-se que a síndrome hemofagocítica é sim um diagnóstico raro, mas que não pode ser descartado quando se apresenta como uma hipótese diagnóstica, já que como discutido é um quadro de gravidade que leva a uma disfunção múltipla dos órgãos de forma súbita.

A pesquisa aborda sobre a nova metodologia de análise do Grau de Alavancagem Financeira das firmas listadas na Bolsa de Valores Brasileira [B]³. A metodologia foi denominada Grau de Alavancagem Financeira – Modificada (GAF-M) e foi construída com base em informações secundárias da plataforma Economatica. A nova metodologia permite que outsiders, analistas financeiros, investidores, acionistas, executivos, bancos e mercado em geral, compreendam o quanto da Alavancagem Financeira está sendo gerado de riqueza ao acionista pela eficiência da operação da firma e não advindo do Planejamento Tributário. O modelo foi capaz de capturar o efeito do planejamento tributário realizado pelas firmas entre os anos de 2018 e 2021, período de análise proposto pelo artigo. Outro ponto apresentado pelo modelo é a existência de uma distinção no Planejamento Tributário entre firmas do Setor Regulado versus o Setor não Regulado. E para finalizar o modelo não identificou variações no planejamento tributário das firmas no auge do pico da pandemia do Covid-19 no ano de 2020.

In the past 20 years, earlier diagnosis and more intensive management have considerably improved the prognosis of rheumatoid arthritis (RA), with milder disease course achieved in particular in seropositive patients. In contrast, seronegative RA has remained largely neglected, and continues to be surrounded by uncertainties regarding its correct diagnosis, clinical phenotype, optimal treatment strategies and relevant outcomes.The purpose of this review is to summarise new insights about the pathogenic, clinical and prognostic peculiarities of seronegative RA that emerged during 2022, and that make this disease subset at least partially different from its seropositive counterpart.

Accurate identification and effective removal of unwanted variation is essential to derive meaningful biological results from RNA sequencing (RNA-seq) data, especially when the data come from large and complex studies. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we examined several sources of unwanted variation and demonstrate here how these can significantly compromise various downstream analyses, including cancer subtype identification, association between gene expression and survival outcomes and gene co-expression analysis. We propose a strategy, called pseudo-replicates of pseudo-samples (PRPS), for deploying our recently developed normalization method, called removing unwanted variation III (RUV-III), to remove the variation caused by library size, tumor purity and batch effects in TCGA RNA-seq data. We illustrate the value of our approach by comparing it to the standard TCGA normalizations on several TCGA RNA-seq datasets. RUV-III with PRPS can be used to integrate and normalize other large transcriptomic datasets coming from multiple laboratories or platforms.

Os cálculos biliares se encontram em mais de 10% da população mundial, sendo que esta incidência se torna maior com o avanço da idade. Sendo assim a colecistite pode ser considerada como uma emergência comum no mundo, sendo que na maior parte dos casos é decorrente da inflamação da parede interna da vesícula devido á impactação do cálculo e decorrente obstrução no ducto cístico, produzindo assim dor repentina e aguda, entretanto a colecistite aguda alitiásica ocorre sem que haja cálculos em seu interior. Esse trabalho possui como sua pergunta de pesquisa qual conduta deve ser adotada para reduzir a taxa de internação em UTI’s em pacientes que apresentem colicistite aguda alitiásica. E assim como seu objetivo geral demonstrar a conduta adequada para manejo de pacientes que apresentem colicistite aguda alitiásica. E como seus objetivos específicos: Identificar do que se trata um quadro de colicistite aguda alitiásica; Auxiliar na tomada de conduta pelos profissionais acerca do tratamento adequado; Disponibilizar informações acerca do assunto. Esse trabalho trata-se de uma revisão sistemática de artigos extraídos das plataformas do PubMed, BVS, Lilacs, Medline, Scielo, esses que possuem datas dos últimos 5 anos e escritos nos seguintes idiomas: português, inglês e espanhol. Com isso conclui-se que ainda são escassos os estudos acerca do tema, portanto é necessário que os médicos consigam de forma significativa o diagnóstico com agilidade, e para isso o conhecimento sobre assunto por uma equipe multidisciplinar deve ser amplamente desenvolvido.

The key role of auxins as integrators of environmental signals has become well-known in recent years, and emerging evidence indicates that auxin biosynthesis is an essential component of the overall mechanisms of plant tolerance to stress. However, although the knowledge of the involvement auxins in the responses related to the generation of roots and accumulation of biomass, studies in ornamental species concerning the commercial propagation in plug cell trays are scarce. Thus, the aim of this work was to evaluate the accumulation of pre-transplant biomass in Impatiens walleriana plants growing in two propagation systems (soilless medium-based plug cell trays and a floating system) with trays of different cell sizes and sprayed either with a single dose of the auxin indole acetic acid (IAA) or with two inhibitors of endogenous auxins, N-1-naphthylphthalamic acid (NPA) and 2,3,5-triiodobenzoic acid (TIBA). Our results demonstrate that plants from both floating system and those sprayed with IAA present both the highest leaf area and fresh and dry weight at the end of the experiment. Conversely, as a negative control, the use of NPA and TIBA as antagonists of the synthesis and translocation of auxins caused an opposite effect in such variables as compared to control plants. However, before making commercial recommendations, it would be necessary to evaluate the potential post-transplant effects of these treatments on the generation of I. walleriana yield. Resumo O papel chave das auxinas como integradores de sinais ambientais tornou-se bem conhecido nos últimos anos e evidências emergentes indicam que a biossíntese de auxinas é um componente essencial dos mecanismos gerais de tolerância das plantas ao estresse. No entanto, apesar do conhecimento do envolvimento das auxinas nas respostas relacionadas à geração de raízes e acúmulo de biomassa, estudos em espécies ornamentais sobre a propagação comercial em bandejas multicelulares são escassos. Assim, o objetivo deste trabalho foi avaliar o acúmulo de biomassa pré-transplante em plantas de Impatiens walleriana cultivadas em dois sistemas (bandejas multicelulares com substrato para plantas sem solo solo e sistema floating) com bandejas de diferentes tamanhos de células e pulverizadas com dose única da auxina ácido indol acético (AIA) ou com dois inibidores de auxinas endógenas, ácido-1-N-naftilftalâmico (NPA) e ácido 2,3,5-triiodobenzóico (TIBA). Nossos resultados demonstram que as plantas no sistema floating e as pulverizadas com AIA apresentam a maior área foliar e massa fresca e seca ao final do experimento. Por outro lado o uso de NPA e TIBA, como antagonistas da síntese e translocação de auxinas, causou efeito oposto nessas variáveis em relação às plantas controle. No entanto, antes de fazer recomendações comerciais, seria necessário avaliar os potenciais efeitos pós-transplante desses tratamentos na geração de produtividade de I. walleriana.

Introdução: O processo de amputação causa relevantes mudanças funcionais nos indivíduos amputados, além de causar complicações que interferem na reabilitação psicomotora e na qualidade de vida do paciente. Somado a isso, grande parcela dos amputados apresentam dor no membro fantasma a curto ou longo prazo, o que prejudica fases da reabilitação. Objetivo: Avaliar a reabilitação física e psicológica de pessoas amputadas através do trabalho multiprofissional visando à reinserção biopsicossocial do paciente. Métodos: Trata-se de estudo exploratório e prospectivo de delineamento transversal quali-quantitativo, onde foram avaliados, pacientes amputados e profissionais de saúde na Associação Norte Paranaense de Reabilitação de Maringá/PR por meio de questionários específicos, baseados na Teoria Cognitivo-Comportamental e em estudos farmacológicos. Os resultados foram armazenados através do Excel 2016 e, posteriormente, analisados com base nos estudos mais atuais sobre o assunto pesquisado. Resultados: A principal causa de amputação dos pacientes foi a diabetes. Além disso, observou-se que o trabalho multiprofissional se mostrou importante para a recuperação física e psicológica dos pacientes. Conclusão: O presente estudo conclui que a abordagem multiprofissional é essencial para a reabilitação do pacientes amputado a fim de promover uma melhora na qualidade de vida e promoção da saúde do paciente.

The protective role against SARS-CoV-2 infection by the third booster dose of mRNA vaccines in cancer patients with solid malignancies is presently unknown. We prospectively investigated the occurrence of COVID-19 in cancer patients on active therapy after the booster vaccine dose.Cancer patients on treatment at the Center for Immuno-Oncology (CIO) of the University Hospital of Siena, Italy, and health care workers at CIO who had received a booster third dose of mRNA vaccine entered a systematic follow-up monitoring period to prospectively assess their potential risk of SARS-CoV-2 infection. Serological and microneutralization assay were utilized to assess levels of anti-spike IgG, and of neutralizing antibodies to the SARS-CoV-2 Wild Type, Delta and Omicron variants, respectively, after the booster dose and after negativization of the nasopharyngeal swab for those who had developed COVID-19.Ninety cancer patients with solid tumors on active treatment (Cohort 1) and 30 health care workers (Cohort 2) underwent a booster third dose of mRNA vaccine. After the booster dose, the median value of anti-spike IgG was higher (p = 0.009) in patients than in healthy subjects. Remarkably, 11/90 (12%) patients and 11/30 (37%) healthy subjects tested positive to SARS-CoV-2 infection during the monitoring period. Similar levels of anti-spike IgG and of neutralizing antibodies against all the investigated variants, with geometric mean titers of neutralizing antibodies against the Omicron being the lowest were detected after the booster dose and after COVID-19 in both Cohorts.The occurrence of SARS-CoV-2 infection we observed in a sizable proportion of booster-dosed cancer patients and in healthy subjects during the Omicron outbreak indicates that highly specific vaccines against SARS-CoV-2 variants are urgently required.

A análise SWOT é uma ferramenta de análise do planejamento estratégico, que auxilia na identificação do ambiente interno (pontos fortes e fracos) e ambiente externo (oportunidades e ameaças), com o intuito de proporcionar a sobrevivência, manutenção, crescimento e desenvolvimento da empresa. Nesse contexto, o presente estudo objetivou analisar uma empresa pelo prisma de seus clientes, a partir da análise de SWOT. A empresa analisada foi uma escola de natação, tendo como público crianças e adultos. Na coleta dos dados foi aplicado aos clientes um questionário estruturado em: aspectos internos (atendimentos, aspectos físicos, piscinas e administrativo) e aspectos externos (outros itens). Realizou-se análise descritiva dos resultados e na sequência o teste de Wilcoxon para validação das hipóteses. Na visão dos usuários, a empresa tem mais pontos fortes do que fracos e, suas oportunidades são maiores do que as ameaças. O trabalho contribui por um olhar diferenciado da utilização da análise de SWOT. Palavras-chave: SWOT. Planejamento Estratégico. Turismo.

This is the accepted manuscript version of the work published in its final form as Fonseca, R., Burn, T. N., Gandolfo, L. C., Devi, S., Park, S. L., Obers, A., Evrard, M., Christo, S. N., Buquicchio, F. A., Lareau, C. A., McDonald, K. M., Sandford, S. K., Zamudio, N. M., Zanluqui, N. G., Zaid, A., Speed, T. P., Satpathy, A. T., Mueller, S. N., Carbone, F. R., & Mackay, L. K. (2022). Runx3 drives a CD8+ T cell tissue residency program that is absent in CD4+ T cells.Nature Immunology,23(8), 1236-1245. https://doi.org/10.1038/s41590-022-01273-4 Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.

Este escrito es a varias voces, desde un entramado de haceres colectivos y de encuentros más allá de las fronteras, encontrando allí narrativas des-centradas, que queremos transcribir, con el fin de poner en palabras los relatos que vamos escuchando en el recorrido de una práctica política activa en el campo de la discapacidad, pero más específicamente con las mujeres con discapacidad que vamos conociendo y reconociendo en el camino. Proponemos hacer aquí, una escritura que rompa algunas lógicas academicistas y capacitistas, para anotar lo que queremos se lea, en clave de resonancias, de lo que vamos acumulando en la escucha. Esta co-producción tampoco reviste el formato de entrevista a una mujer con discapacidad, porque denunciamos en cada ocasión, las acciones extractivistas que muchas veces asumen algunas prácticas, sino que la asumimos como una conversación de afectaciones mutuas.

Technical information about deep foundations of built structures may in some cases be unavailable or incomplete due to the lack of construction documentation and electronic media in which the reports are stored. This problem is particularly relevant for telecommunication towers constructed two-to-three decades ago but still under operation and subject to new loading demands from expanding networks. Nondestructive evaluation with geophysical methods has been applied to determine the depth to the bottom of deep foundations, a key parameter to evaluate their bearing capacity and settlements. This is done by lowering a borehole magnetometry (BM) sensor down a drillhole installed close to the unknown structure, thereby measuring the magnetic field along the testing drillhole. Determining the bottom depth of the structure using BM data configures an edge detection problem: a classical problem in magnetic data interpretation, but in this case with poor data coverage (only a profile close to the structure) to characterize a complex magnetization distribution. Common practices to locate pile bottom from characteristic peak or inflection points in the observed magnetic anomaly may work at some sites but usually fail to account for the complex anomaly patterns from built structures. We summarize a set of numerical and field-work applications showing that no single characteristic attribute of the observed field can undoubtedly be used to determine the foundation depth. We verify that most of the measured field along the testing drillhole is disturbed by fields from facilities at the ground surface and develop a data inversion procedure enforcing data fitting to measurements at the lower portions of the drillhole. The efficacy of this technique is illustrated with field tests in different geologic scenarios with results compared with as-built documentation and/or independent evaluation with other methods.

El presente trabajo tiene como objetivo analizar el diseño curricular de un programa de formación de profesores de Física en relación con las oportunidades que ofrece para el desarrollo del conocimiento pedagógico del contenido (CPC) de los alumnos. En particular, se hace foco en el currículo de los espacios curriculares relacionados con los contenidos disciplinares. Se pretende identificar las oportunidades que el currículo de estas asignaturas ofrece para el desarrollo del CPC de los estudiantes. El estudio se realiza sobre el currículo del profesorado de Física del Instituto de Educación Superior Simón Bolívar, de la ciudad de Córdoba, Argentina. A través del análisis, se detectan instancias en las que el currículo ofrece oportunidades para fortalecer el CPC de los futuros docentes, pero también existen carencias que pueden ser abordadas en futuras elaboraciones del mismo.

Methanol is a fuel that can be produced using renewable electricity, green hydrogen, and a carbon-neutral carbon source. As a low-carbon liquid fuel, methanol is a leading candidate as a drop-in replacement fuel for rapid decarbonization of the transportation sector. In this work, methanol is tested experimentally in mixing-controlled compression ignition using a single-cylinder research engine. Specifically, the impact of a double injection strategy and high exhaust gas recirculation (EGR) dilution on performance and emissions parameters are studied. As a single-carbon, oxygenated fuel, methanol has a near-zero sooting potential, meaning there is no soot-NOx tradeoff as EGR dilution is increased. EGR dilution effectively reduces NOx emissions without a significant combustion efficiency or thermal efficiency penalty until the global equivalence ratio exceeds 0.9, at which point, a significant combustion efficiency penalty is incurred in the form of increased CO emissions. If stoichiometric operation with high EGR dilution is considered, engine-out NOx emissions are low, even at very high loads, and NOx aftertreatment is simplified through the use of a three-way catalyst. However, a relative decrease in the net fuel conversion efficiency of up to 8.5% was observed, demonstrating an emissions-efficiency tradeoff. Under lean and stoichiometric conditions, no appreciable agglomeration of particulate matter was observed.

Two distinct types of fossil infructescences from the early Eocene Laguna del Hunco flora, Chubut Province, Patagonia, Argentina, preserve features of the family Cunoniaceae. The goal of the study was to assess their affinities within Cunoniaceae and to interpret their evolutionary and biogeographical significance.Specimens were collected from the Tufolitas Laguna del Hunco, Huitrera Formation. They were prepared, photographed, and compared morphologically with similar extant and fossil fruits and infructescences using published literature and herbarium material.The fruit and infructescence morphology place the fossil taxa within Cunoniaceae. They do not conform to any extant genus, supporting the erection of two new fossil genera. Racemofructus gen. nov. shares diagnostic features of the tribe Cunonieae, especially Weinmannia s.l., and exhibits two tribal morphological synapomorphies: a racemose inflorescence and a replum composed of a single column. Cunoniocarpa gen. nov. specimens are paniculate inflorescences with basipetally dehiscent, bicarpellate capsules that have persistent styles and calyces. Its replum morphology suggests an affinity to the tribe Caldcluvieae, particularly to the genus Ackama.The new Patagonian fossils described herein constitute the oldest record of cunoniaceous capsules globally, supplementing a significant body of fossil evidence from pollen, wood, and reproductive structures from southern South America and Antarctica that suggests that the Cunoniaceae were diversified and widely distributed in the southern hemisphere by the early Eocene. Racemofructus and Cunoniocarpa are, respectively, the first fossil records from South America of reproductive structures with affinity to tribes Cunonieae and Caldcluvieae.

Peripheral immune-checkpoint blockade with mAbs to programmed cell death receptor-1 (PD-1) (either nivolumab or pembrolizumab) or PD-Ligand-1 (PD-L1) (atezolizumab, durvalumab, or avelumab) alone or in combination with doublet chemotherapy represents an expanding treatment strategy for metastatic non-small cell lung cancer (mNSCLC) patients. This strategy lays on the capability of these mAbs to rescue tumor-specific cytotoxic T lymphocytes (CTLs) inactivated throughout PD-1 binding to PD-L1/2 in the tumor sites. This inhibitory interactive pathway is a physiological mechanism of prevention against dangerous overreactions and autoimmunity in case of prolonged and/or repeated CTL response to the same antigen peptides. Therefore, we have carried out a retrospective bioinformatics analysis by single-cell flow cytometry to evaluate if PD-1/PD-L1-blocking mAbs modulate the expression of specific peripheral immune cell subsets, potentially correlated with autoimmunity triggering in 28 mNSCLC patients. We recorded a treatment-related decline in CD4+ T-cell and B-cell subsets and in the neutrophil-to-lymphocyte ratio coupled with an increase in natural killer T (NKT), CD8+PD1+ T cells, and eosinophils. Treatment-related increase in autoantibodies [mainly antinuclear antibodies (ANAs) and extractable nuclear antigen (ENA) antibodies] as well as the frequency of immune-related adverse events were associated with the deregulation of specific immune subpopulations (e.g., NKT cells). Correlative biological/clinical studies with deep immune monitoring are badly needed for a better characterization of the effects produced by PD-1/PD-L1 immune-checkpoint blockade.

Navigating our complex social world requires processing the interactions we observe. Recent psychophysical and neuroimaging studies provide parallel evidence that the human visual system may be attuned to efficiently perceive dyadic interactions. This work implies, but has not yet demonstrated, that activity in body-selective cortical regions causally supports efficient visual perception of interactions. We adopt a multi-method approach to close this important gap. First, using a large fMRI dataset (N=92), we found that the left-hemisphere Extrastriate Body Area (EBA) responds more to face-to-face than non-facing dyads. Second, we replicated a behavioural marker of visual sensitivity to interactions: categorisation of facing dyads is more impaired by inversion than non-facing dyads. Third, we used fMRI-guided transcranial magnetic stimulation to show that online stimulation of the left EBA, but not a nearby control region, abolishes this selective inversion effect. Activity in left EBA, thus, causally supports the efficient perception of social interactions.

Introduction: Tricuspid regurgitation (TR) is a relatively common valvular disease, which can result from structural abnormalities of any anatomic part of the tricuspid valve. Severe TR is linked to congestive heart failure and hemodynamic impairment, resulting in high mortality when repaired by elective surgery. This study was undertaken to quantify the structural and hemodynamic performance of the novel Transcatheter Bicaval Valves System (TricValve) percutaneously implanted in the superior vena cava (SVC) and inferior vena cava (IVC) of two patients with severe TR and venous congestion.Methods: After developing the SVC and IVC device models, the contact pressure exerted on the vena cava wall was obtained by computational analysis. Both smoothed-particle hydrodynamics (SPH) and computational fluid dynamics were carried out to quantify caval reflux in the right atrium and the pressure field of pre- and post-TricValve scenarios, respectively.Results: Analysis of contact pressure highlighted the main anchoring area of the SVC device occurring near the SVC device belly, while the IVC device exerted pronounced forces in the device’s proximal and distal parts. SPH-related flow velocities revealed the absence of caval reflux, and a decrease in time-averaged pressure was observed near the SVC and IVC after TricValve implantation.Discussion: Findings demonstrated the potential of computational tools for enhancing our understanding of the biomechanical performance of structural tricuspid valve interventions and improving the way we design next-generation transcatheter therapies to treat the tricuspid valve with heterotopic caval valve implantation.

The use of animal-based fertilizers in the forms of manure and slurry is widespread throughout Europe. The process of spreading manure and slurry results in large emissions of greenhouse gases as well as inorganic gases and volatile organic compounds (VOCs). The non-methane VOCs emitted from manure and slurry are not well characterized, even though they are expected to result in the formation of important secondary pollutants such as ozone and secondary organic aerosols (SOA). In this study, we conducted an initial small-scale laboratory measurement of VOCs emitted by cattle slurry using a Time of Flight Chemical Ionisation Mass Spectrometer. Dry purified air was passed through a small chamber containing the slurry and into the instrument, which was operated using both C6H6+ and I- as reagent ions in order to detect a large range of oxygenated and hydrocarbon VOCs. Using the I- reagent ion, a number of low molecular weight carboxylic acids were detected, along with some phenolic compounds and hydrogen disulfide. A much larger number of compounds was detected using the C6H6+reagent ion, including the same phenolic compounds and a range of nitrogen-containing species. The timescales of the emitted species showed considerable variation, with some, e.g. hydrogen disulfide, being very intense and short-lived, and others, e.g. phenol, being continuously emitted at a roughly constant rate for several hours. Further work is currently underway to understand the factors controlling the nature of these emissions, their reactivity and SOA formation.

Renewable fuels, such as the alcohols, ammonia, and hydrogen, have a high autoignition resistance. Therefore, to enable these fuels in compression ignition, some modifications to existing engine architectures is required, including increasing compression ratio, adding insulation, and/or using hot internal residuals. The opposed-piston two-stroke (OP2S) engine architecture is unique in that, unlike conventional four-stroke engines, the OP2S can control the amount of trapped residuals over a wide range through its scavenging process. As such, the OP2S engine architecture is well suited to achieve compression ignition of high autoignition resistance fuels. In this work, compression ignition with wet ethanol 80 (80% ethanol, 20% water by mass) on a 3-cylinder OP2S engine is experimentally demonstrated. A load sweep is performed from idle to nearly full load of the engine, with comparisons made to diesel at each operating condition. These results indicate that on the OP2S architecture, wet ethanol 80 produces near-zero soot and reduces engine-out NOx emissions by a factor of 3-5. Due to the combustion chamber geometry, which is optimized for diesel combustion, most of the fuel was injected near top dead center for a diffusion-style heat release process. Therefore, there is 1-3 percentage point thermal efficiency penalty associated with wet ethanol 80’s longer diffusion heat release process, since the nozzle hole size of the injector was not increased, and from evaporation-driven heat removal near top dead center. However, further optimization of the injectors and combustion chamber geometry could mitigate or eliminate this efficiency penalty by enabling a larger fraction of the total fuel to be injected earlier in the compression stroke.

Spark ignition knock is highly sensitive to changes in intake air temperature. Hot surface temperatures due to ceramic thermal barrier coatings increase knock propensity by elevating the incoming air temperature, thus mitigating the positive impacts of low heat transfer losses by requiring spark retard to avoid knock. Low thermal inertia coatings (i.e. Temperature swing coatings) have been proposed as a means of reducing or eliminating the open cycle charge heating penalty of traditional TBCs through a combination of low thermal conductivity and low volumetric heat capacity materials. However, in order to achieve a meaningful gain in efficiency, a significant fraction of the combustion chamber must be coated. In this study, a coated piston and intake and exhaust valves with coated combustion faces, backsides, and stems are installed in a single-cylinder research engine to evaluate the effect of high coated fractions of the combustion chamber in a knock-sensitive architecture. Spark timing sweeps demonstrated a small, but notable increase in net thermal efficiency compared to the coated piston by itself. A staged valve removal demonstrated that the coated intake valve prevents heat transfer to the incoming air, reducing knock propensity compared to the coated exhaust valve individually.

Spark ignition engines have low tailpipe criteria pollutants due to their stoichiometric operation and three-way catalysis and are highly controllable. However, one of their main drawbacks is that the compression ratio is low due to knock, which incurs an efficiency penalty. With a global push towards low-lifecycle-carbon renewable fuels, high-octane alternatives to gasoline such as ethanol are attractive options as fuels for spark ignition engines. Under premixed spark ignition operating conditions, ethanol can enable higher compression ratios than regular-grade gasoline due to its high octane number. The high cooling potential of high-ethanol content gasolines, like E85, or of ethanol-water blends, like hydrous ethanol, can be leveraged to further reduce knock and enable higher compression ratios as well as further downsizing and boosting to reduce frictional and throttling losses.In this work, a split injection strategy is used, where 5-15% of the total injected fuel is injected during the compression stroke with E75 gasoline (75% ethanol, by volume) and hydrous ethanol (190 proof ethanol, 92% ethanol, 8% water, by mass). These experimental results indicate that injecting a small amount of E75 or WE92 during the middle of the compression stroke such that the fuel cannot completely homogenize with the air before the spark fires results in knock mitigation that exceeds the amount of knock mitigation expected by evaporating that amount of fuel in air in a premixed setting. This split injection strategy achieved a 1.3% relative fuel conversion efficiency benefit with E75 at 19 bar IMEPn and a 1.4% relative fuel conversion efficiency benefit at 15 bar IMEPn with WE92. Overall, these results indicate that a split injection strategy with a high cooling potential alcohol fuel can further increase a fuel’s effective octane number, enabling highly boosted, high compression ratio stoichiometric spark ignition operation.

Supplementary Methods

Supplementary Tables S1-5

Supplemental FIGS S4 - S5 - Summary of vascular density, vascular patentcy and tissue hypoxia measurements following camptothecin treatment.

Supplemental FIGS S1 & S2 - Whole tissue section images comparing drug extravasation in HCT116 and HT29 xenografts.

Supplementary Table S8

Supplemental FIG S3 - Whole tissue section images comparing irinotecan extravasation versus MRI based contrast agent localization.

Supplementary Table S7

Supplementary Table S6

Supplementary Figures

Supplementary Table S9

Background US-indeterminate adnexal lesions remain an important indication for gynecologic surgery. MRI can serve as a problem-solving tool through the use of the Ovarian-Adnexal Imaging Reporting and Data System (O-RADS) MRI lexicon, which is based on the ADNEX MR scoring system. Purpose To perform a systematic review and meta-analysis of the diagnostic performance of pelvic MRI interpreted using the ADNEX or O-RADS MRI stratification systems to characterize US-indeterminate adnexal lesions and of the category-wise malignancy rates. Materials and Methods A systematic literature search from May 2013 (publication of the ADNEX MR score) to September 2022 was performed. Studies reporting the use of pelvic MRI interpreted with the ADNEX or O-RADS MRI systems to characterize US-indeterminate adnexal lesions, with pathologic examination and/or follow-up as the reference standard, were included. Summary estimates of diagnostic performance were obtained with the bivariate random-effects model, while category-wise summary malignancy rates of O-RADS MRI 2, 3, 4, and 5 lesions were obtained with a random-effects model. Effects of covariates on heterogeneity and diagnostic performance were investigated through meta-regression. Results Thirteen study parts from 12 studies (3731 women, 4520 adnexal lesions) met the inclusion criteria. Diagnostic performance meta-analysis for 4012 lesions found a 92% summary sensitivity (95% CI: 88, 95) and a 91% summary specificity (95% CI: 89, 93). The meta-analysis of malignancy rates for 3641 lesions showed summary malignancy rates of 0.1% (95% CI: 0, 1) among O-RADS MRI 2 lesions, 6% (95% CI: 3, 9) among O-RADS MRI 3 lesions, 60% (95% CI: 52, 67) among O-RADS MRI 4 lesions, and 96% (95% CI: 92, 99) among O-RADS MRI 5 lesions. Conclusion Pelvic MRI interpreted with the Ovarian-Adnexal Reporting and Data System (O-RADS) MRI lexicon had high diagnostic performance for the characterization of US-indeterminate adnexal lesions. Summary estimates of malignancy rates in the O-RADS MRI 4 and O-RADS MRI 5 categories were higher than predicted ones. © RSNA, 2022

BackgroundDespite the latest advances in prenatal diagnosis and postnatal embolization procedures, intracranial arteriovenous shunts (AVSs) are still associated with high mortality and morbidity rates. Our aim was to evaluate the presentation and clinical course, the neurodevelopmental outcome, and the genetic findings of neonates with AVSs.MethodsIn this retrospective observational study, medical records of neonates with cerebral AVSs admitted to our hospital from January 2020 to July 2022 were revised. In particular, we evaluated neuroimaging characteristics, endovascular treatment, neurophysiological features, neurodevelopmental outcomes, and genetic findings.ResultsWe described the characteristics of 11 patients with AVSs. Ten infants (90.9%) required embolization during the first three months of life. In 5/9 infants, pathological electroencephalography findings were observed; of them, two patients presented seizures. Eight patients performed Median Nerve Somatosensory Evoked Potentials (MN-SEPs): of them, six had an impaired response. We found normal responses at Visual Evoked Potentials and Brainstem Auditory Evoked Potentials. Eight patients survived (72.7%) and were enrolled in our multidisciplinary follow-up program. Of them, 7/8 completed the Bayley-III Scales at 6 months of corrected age: none of them had cognitive and language delays; conversely, a patient had a moderate delay on the Motor scale. The remaining survivor patient developed cerebral palsy and could not undergo Bayley-III evaluation because of the severe psychomotor delay. From the genetic point of view, we found a novel pathogenic variant in the NOTCH3 gene and three additional genomic defects of uncertain pathogenicity.ConclusionWe propose SEPs as an ancillary test to discern the most vulnerable infants at the bedside, particularly to identify possible future motor impairment in follow-up. The early identification of a cognitive or motor delay is critical to intervene with personalized rehabilitation treatment and minimize future impairment promptly. Furthermore, the correct interpretation of identified genetic variants could provide useful information, but further studies are needed to investigate the role of these variants in the pathogenesis of AVSs.