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Abstract As the world races to decarbonize power systems to mitigate climate change, the body of research analyzing paths to zero emissions electricity grids has substantially grown. Although studies typically include commercially available technologies, few of them consider offshore wind and wave energy as contenders in future zero-emissions grids. Here, we model with high geographic resolution both offshore wind and wave energy as independent technologies with the possibility of collocation in a power system capacity expansion model of the Western Interconnection with zero emissions by 2050. In this work, we identify cost targets for offshore wind and wave energy to become cost effective, calculate a 17% reduction in total installed capacity by 2050 when offshore wind and wave energy are fully deployed, and show how curtailment, generation, and transmission change as offshore wind and wave energy deployment increase.

La enfermedad de Kawasaki (EK) es una enfermedad febril aguda y autolimitada y es la principal causa de cardiopatía adquirida pediátrica en países desarrollados. Cursa con fiebre mayor a cinco días, alteraciones en mucosa oral, linfadenopatías, rash, compromiso de miembros y/o inyección conjuntival. Puede haber compromiso hepático que puede abarcar desde un aumento leve de transaminasas hasta hepatitis colestásica grave y/o hidrops vesicular. Se presenta a una paciente de 5 años cuyo cuadro inició con una hepatitis febril aguda colestásica, sin causa aparente. Al día 14 de evolución agregó inyección conjuntival no purulenta, descamación periungueal y trombocitosis. Ante la sospecha de EK atípica se realizó ecocardiograma que informó afección coronaria. Resulta importante tener en cuenta la variabilidad de síntomas en la EK ya que la rápida instauración del tratamiento adecuado disminuye la aparición y gravedad de las complicaciones asociadas.

Background: Diagnostic excellence encompasses both receiving an accurate and timely explanation of a health problem that was communicated well, and the process it took to get to the correct diagnosis. Directly eliciting patients’ perceptions of their diagnostic experience and outcomes after emergency visits is a promising method of assessing diagnostic excellence. However, little is known about how patients interpret and respond to questions about their diagnostic experiences and outcomes. Objective: To analyze patient and care partners’ interpretation of questions capturing patient-reported diagnostic excellence in emergency settings. Design: Cognitive interviews using think-aloud and probing methods. Setting(s): Interviews were conducted virtually and via phone calls. Participants were patients or care partners of patients recently discharged from three emergency departments within a single academic health system in the Mid-Atlantic region of the US. Participants: 15 patients and care partners, 18 years or older, with recent emergency department experiences. Methods: Qualitative analysis using a deductive approach was used to code transcripts and analyze participant responses to Patient-Report to Improve Diagnostic Excellence in Emergency Department (PRIME-ED) questionnaire items. Themes of patient and care partners’ questionnaire interpretations are presented descriptively. Results: 80% of participants were female, 47% were between the ages of 18–24 years, 47% of participants were White, and 7% were Hispanic/Latino. Participants shared their interpretations of diagnostic excellence following PRIME-ED domains: diagnostic accuracy and care team skills, their comprehension of the diagnosis, provider communication of uncertainty, and quality of diagnostic communication, including whether they felt the care team communicated well, adapted communication to their needs, listened and took concerns seriously, treated them as an equal, and provided clear, sufficient, and functional communication about follow-up steps. Responses indicated that patients and care partners can identify diagnostic errors, rationalize why their diagnosis was inaccurate, and assess whether diagnostic excellence was achieved. Respondents identified factors that contributed to their assessments of diagnostic accuracy and the quality of diagnostic communication. The quality of diagnostic communication contributed to patient perception of diagnostic accuracy and understanding of the diagnosis. Conclusions: Patient report is a useful tool for assessing diagnostic excellence in emergency settings. Our patient and care partners describe how they assess diagnostic excellence in the emergency department.Registration: N/A.Tweetable abstract: Patients and care partners provide accessible and useful information to assess diagnostic practices and diagnostic excellence in emergency departments.

Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune cytokine that belongs to the TNF superfamily of receptor ligands. The cytokine exists as either a transmembrane or a soluble molecule, and targets two distinct receptors, TNF-α receptor 1 (TNFR1) and TNF-α receptor 2 (TNFR2), which activate different signaling cascades and downstream genes. TNF-α cellular responses depend on its molecular form, targeted receptor, and concentration levels. TNF-α plays a multifaceted role in normal physiology that is highly relevant to human health and disease. In the central nervous system (CNS), this cytokine regulates homeostatic functions, such as neurogenesis, myelination, blood-brain barrier permeability and synaptic plasticity. However, it can also potentiate neuronal excitotoxicity and CNS inflammation. The pleiotropism of TNF-α and its various roles in the CNS, whether homeostatic or deleterious, only emphasizes the functional complexity of this cytokine. Anti-TNF-α therapy has demonstrated effectiveness in treating various autoimmune inflammatory diseases and has emerged as a significant treatment option for CNS autoimmune diseases. Nevertheless, it is crucial to recognize that the effects of this therapeutic target are diverse and complex. Contrary to initial expectations, anti-TNF-α therapy has been found to have detrimental effects in multiple sclerosis. This article focuses on describing the various roles, both physiological and pathological, of TNF-α in the CNS. Additionally, it discusses the specific disease processes that are dependent or regulated by TNF-α and the rationale of its use as a therapeutic target.

Transverse myelitis (TM) is the second most common presentation of myelin oligodendrocyte antibody-associated disease (MOGAD), occurring in approximately 26% of affected patients. The diagnosis may be complicated by the lack of diagnostic specificity of low titers of MOG antibody in serum, fluctuation in seropositivity overtime, including initially normal MRI in up to 10% of patients, and in many instances complete resolution of radiological abnormalities when MRI is done in a significantly delayed fashion. The use of preventive disease modifying treatments is limited by the uncertainty whether the disease process will remain monophasic or become relapsing, as well as by the lack FDA approved treatments. In this review, we discuss clinical, radiological and cerebrospinal fluid (CSF) characteristics, including the significance of MOG titers and changes in the seropositivity status for the diagnosis of MOGAD-associated TM, its radiological features and management options, highlighting the data on the risk of relapses associated with TM at presentation and the need for further randomized clinical trials to empower effective treatment algorithms.

Human papillomavirus (HPV) is a known cause of cervical cancer. Here, the authors perform a multi-omic analysis using published cervical squamous cell carcinoma cohorts from the USA, Europe, and SubSaharan Africa and identify two cervical squamous cell carcinoma subtypes that display prognostic differences.

Background: It is unclear what is responsible for the large variations in the prevalence of meningococcal resistance to cephalosporins and quinolones. Methods: We used mixed-effects linear regression to assess if country-level prevalence of reduced susceptibility to cefotaxime and ciprofloxacin was associated with the population-level consumption of cephalosporins and quinolones in 13 European countries. Results: Positive correlations were found between the prevalence of reduced susceptibility to ciprofloxacin and the consumption of quinolones (coef. 0.16, 95% CI 0.05–0.27; P = 0.003). The same positive association was found for cefotaxime/cephalosporins (coef. 0.1, 95% CI 0.04–0.15; P = 0.001). Conclusions: Meningococcal reduced susceptibility to cefotaxime and ciprofloxacin is linked to homologous class antimicrobial consumption. This finding provides additional motivation for strengthening antimicrobial stewardship programs.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory condition that presents with fever, hepatosplenomegaly, and characteristic laboratory findings. Mutations in the perforin gene PRF1 have been implicated in cases of familial HLH (fHLH) and can cause isolated CNS-HLH in the absence of systemic HLH. Results: A five year-old boy presented with three weeks of headache, blurry vision, and emesis. He was diagnosed with acute disseminated encephalomyelitis (ADEM), thought to be triggered by SARS-CoV-2 given positive nasopharyngeal testing. He completed a five day course of high dose IV methylprednisolone and plasma exchange. In the subsequent months, he was admitted twice due to worsening clinical and radiological activity and after several courses of IV pulse steroids, plasmapheresis, and IV immunoglobulin (IVIG), his condition stabilized with rituximab and monthly IVIG. A few months later, his younger brother presented with a similar syndrome. It was discovered that his parents were second cousins, leading to concern for a genetic disorder. Genetic testing revealed a homozygous mutation for PRF1 in both siblings (variant c.4422G>A). Conclusions: This is the first presentation of CNS-isolated familial HLH triggered by SARS-CoV-2 in the pediatric population. Furthermore, this is the first report of this specific PRF1 mutation, the variant c.4422G>A, as pathogenic. It highlights the relevance of genetic testing in pediatric neuroinflammatory disorders that do not respond adequately to conventional treatments. It is possible that as our knowledge in neurogenetics develops, certain genes will be identified as predisposing factors to syndromes such as ADEM.

Introducción: El Carcinoma oral de células escamosas es la patología oral maligna de mayor frecuencia, representa el 2 al 3% de todas las neoplasias y hasta el 80-90% de las de la cavidad bucal, se define como una neoplasia maligna invasiva epitelial que invade el corion subyacente, con gran tendencia a metastatizar a ganglios linfáticos. En su etiología se asocia principalmente a factores como tabaco, alcohol y virus del papiloma humano, siendo más frecuente en adultos masculinos entre la 5ta y 6ta década de la vida. Objetivos: El objetivo del estudio fue determinar el perfil del Carcinoma Oral de Células Escamosas, en el Laboratorio de Anatomía Patológica de la Facultad de Odontología de la Universidad de la República en el período 1982-2015. Materiales y métodos: Se realizó un estudio retrospectivo, transversal y analítico utilizando para el análisis estadístico el modelo de Cox, el test exacto de Fisher y el método de Kaplan-Meier para la sobrevida. Resultados: De los 207 casos el 59,9% fueron hombres, el 98.5% mayores de 40 años, con una media de 63 años ± 12,57. Se localizó preferentemente en la lengua, con predominio de los carci- nomas bien diferenciados y moderadamente diferenciados, desde el punto de vista histopatológico. Se encontró asociación entre el grado histopatológico, género y edad; con un tiempo medio de sobrevida de 2.36 años y una tasa de sobrevida del 43% a los 5 años. Discusión y conclusiones: En general los datos reportados en la literatura coinciden con los resultados del presente estudio, habiendo diferencias en la topografía y la relación entre los géneros, con la tendencia en aumento en las mujeres. Se determinó que los hombres presentaban mayor proporción de carcinomas moderadamente diferenciados y las mujeres carcinomas bien diferenciados; y que a mayor edad, mayor proporción de carcinomas indiferenciados, pudiendo relacionarse con el avance de la enfermedad. De la misma forma, el avance de la patología, podría explicar cómo los carcinomas moderadamente diferenciados presentaron casi el doble de riesgo de fallecer que los bien diferenciado, con todos los pacientes con carcinomas indiferenciados fallecidos a los 7 años del seguimiento.

Background: Commensal Neisseria species (spp). represent an important reservoir of antimicrobial resistance genes for pathogenic Neisseria spp. In this systematic review, we aimed to assess the antimicrobial susceptibility of commensal Neisseria spp. and how this has evolved over time. We also aimed to assess if commensal Neisseria spp. showed intrinsic resistance to four antimicrobials - penicillin, azithromycin, ceftriaxone and ciprofloxacin. Methods: Pubmed and Google Scholar were searched following the PRISMA guidelines. Articles reporting MICs of commensal Neisseria spp. were included according to inclusion/exclusion criteria, and the quality of the articles was assessed using a pre-designed tool. Individual and summary measures of penicillin, azithromycin, ceftriaxone and ciprofloxacin MICs were collected. Additional data was sought to perform a comparison between the MICs of pathogenic and commensal Neisseria spp. Results: A total of 15 studies met our criteria.We found no evidence of intrinsic AMR in commensal Neisseria spp. We did find evidence of an increasing trend in MICs of commensal Neisseria spp. over time for all antimicrobials assessed. These findings were similar in various countries. Eight additional studies were included to compare pathogenic and commensal Neisseria spp. Conclusion: The MICs of commensal Neisseria spp. appear to be increasing in multiple countries. Surveillance of MICs in commensals could be used as an early warning system for antimicrobial resistance emergence in pathogens. Our findings underline the need for antibiotic stewardship interventions, particularly in populations with high antimicrobial consumption.

Abstract Background The retinal microcirculation has been studied in various diseases including multiple sclerosis (MS). However, inter-eye correlations and potential differences of the retinal blood flow velocity (BFV) remain largely unstudied but may be important in guiding eye selection as well as the design and interpretation of studies assessing or utilizing retinal BFV. The primary aim of this study was to determine inter-eye correlations in BFVs in healthy controls (HCs). Since prior studies raise the possibility of reduced BFV in MS eyes, a secondary aim was to compare retinal BFVs between MS eyes, grouped based on optic neuritis (ON) history and HC eyes. Methods Macular arteriole and venule BFVs were determined using a retinal function imager (RFI) in both eyes of 20 HCs. One eye from a total of 38 MS patients comprising 13 eyes with ON (MSON) and 25 eyes without ON (MSNON) history were similarly imaged with RFI. Results OD (right) and OS (left) BFVs were not significantly different in arterioles (OD: 3.95 ± 0.59 mm/s; OS: 4.08 ± 0.60 mm/s, P = 0.10) or venules (OD: 3.11 ± 0.46 mm/s; OS: 3.23 ± 0.52 mm/s, P = 0.06) in HCs. Very strong inter-eye correlations were also found between arteriolar (r = 0.84, P

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing–remitting MS (RRMS). Methods: DMT efficacy related to age was assessed through a meta-analysis of clinical trials that evaluated the efficacy of DMTs in RRMS patients as measured by reductions in the annualized relapse rate (ARR), new T2 lesions, and gadolinium-enhanced lesions on MRI. Using the mean baseline patient age from each trial, a weighted linear regression was fitted to determine whether age was associated with treatment efficacy on a group level. Results: Group-level data from a total of 28,082 patients from 26 trials of 14 different DMTs were included in the meta-analysis. There were no statistically significant associations between age and reductions in ARR, new T2 lesions, and gadolinium-enhanced lesions of the treatment group compared with placebo. Conclusion: DMTs for RRMS show efficacy in treating disease activity independent of age as demonstrated by group-level data from DMT clinical trials. Nevertheless, clinical trials select for patients with baseline disease activity regardless of age, thereby not representing real-world patients with RRMS, where disease activity declines with age.

Antibiotic-sparing treatments are required to prevent the further emergence of antimicrobial resistance in Neisseria gonorrhoeae. Commensal Neisseria species have previously been found to inhibit the growth of pathogenic Neisseria species. For example, a previous study found that three out of five historical isolates of Neisseria mucosa could inhibit the growth of N. gonorrhoeae. In this study, we used agar overlay assays to assess if 24 circulating and historical isolates of Neisseria mucosa could inhibit the growth of 28 circulating and historical isolates of N. gonorrhoeae. Although pitting around each colony of N. mucosa created an optical illusion of decreased growth of N. gonorrhoeae, we found no evidence of inhibition (n = 24). In contrast, positive controls of Streptococcus pneumoniae and Escherichia coli demonstrated a strong inhibitory effect against the growth of N. gonorrhoeae.

This report aims to enhance the understanding of early longitudinal neuroimaging features of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV). Neuroimaging has become crucial in the diagnosis and early recognition of PML. Recognition of magnetic resonance imaging (MRI) features in the early stages of PML is paramount to avoid misdiagnosis and facilitate the delivery of treatments aimed at reducing disease progression. A 49-year-old white man with HIV presented with 4-month progressive left-sided weakness. Neurological examination revealed mild cognitive impairment, left-sided hemiparesis, and somatosense impairment to all modalities. Brain MRI revealed a punctate pattern with innumerable T2-FLAIR (fluid attenuated inversion recovery) hyperintensities in the cortex, brainstem, cerebellum, subcortical, and periventricular areas. Susceptibility-weighted imaging (SWI) revealed hypointensities involving subcortical U-fibers and cortical architecture. A comprehensive diagnostic evaluation was inconclusive. John Cunningham virus (JCV) PCR in cerebrospinal fluid (CSF) was indeterminate. He was started on antiretroviral therapy. Repeat brain MRI performed 1.5 months later, in the setting of further neurological decline, demonstrated progression of the T2-hyperintensities into a large confluent white matter lesion in the right frontoparietal lobe. Despite an indeterminate JCV PCR, the appearance and characteristic progression of the lesions in successive imaging in the setting of severe immunosuppression, with extensive negative infectious workup, was indicative of PML. This clinical experience illustrates unique neuroimaging features of HIV-PML in early stages and its progression over time. It especially highlights the relevance of the SWI sequence in the diagnosis and features observed with disease evolution. Short-term imaging follow-up may assist with the recognition of MRI features consistent with the biology of the infection.

Abstract Purpose To review the clinical and research value of optical coherence tomography angiography (OCTA) in the field of neurology. Methods Current literature involving OCTA were reviewed through PubMed using the search terms “optical coherence tomography angiography”, with “multiple sclerosis”, “Alzheimer’s disease”, “optic neuropathy”, or other closely-related terms. Results OCTA has been applied in research to advance our understanding of the pathobiology of neurological disorders. OCTA-derived blood flow and vessel density measures are altered in multiple sclerosis (MS), Alzheimer’s disease (AD), and various optic neuropathies (ON) in varying regions of the posterior segment vasculature of the eye. These emerging research findings support the occurrence of retinal vascular alterations across a host of neurological disorders and raise the possibility that vasculopathy can be clinically relevant since it contributes to the pathobiology of several neurological disorders. Conclusion OCTA may be beneficial for neurological research. Additional investigations using OCTA in neurological disorders will help to further validate its clinical and research utilities in terms of characterizing the role of vasculopathy in neurological disorders.

Los dispositivos móviles como los smartphones, están determinando y repercutiendo en muchas de las dinámicas familiares y comunicacionales entre padres e hijos. El uso que los propios progenitores realizan de dicho dispositivo, en muchas ocasiones, puede generar vulnerabilidad en los menores. En este artículo se presenta una investigación cualitativa, en la que se ha realizado un análisis documental de las investigaciones nacionales e internacionales sobre la temática con la finalidad de identificar los riesgos a los que se enfrentan los menores cuando los progenitores utilizan el Smartphone en el contexto familiar. Los resultados destacan, entre las principales problemáticas los accidentes de tráfico, y la repercusión de la frecuencia de uso del dispositivo en las distracciones parentales y los efectos negativos sobre las relaciones paterno-filiares.

La filosofía consumista de la sociedad contemporánea sumada a una proliferación de medios tecnológicos virtuales que hacen más fácil la obtención de objetivos deseados, conduce a un aumento de conductas adictivas que trascenden al espectro de adiciones clásicas a sustancias psicoactivas químicas. Actualmente, se observan cada vez con mayor frecuencia las conductas adictivas relacionadas con aspectos de la vida cotidiana como medios tecnológicos, compras, cuidado corporal, trabajo, entre otros. En este orden de ideas, las actitudes que presentan los niños y adolescentes en relación a conductas adictivas son de gran importancia ya que constituyen un factor de riesgo que sumado a cierto tipo de circunstancias, podrá llevar al desarrollo de conductas adictivas en el futuro. El artículo expone resultados de un estudio orientado a indagar por las actitudes de favorabilidad hacia conductas adictivas, prevalentes en una muestra de adolescentes entre 12 y 18 años de algunas instituciones educativas de Medellín y Riosocio. El estudio de corte cuantitativo, nivel descriptivo, contó con una muestra de 92 estudiantes en edades entre 12 y 19 años, se empleo una escala Likert diseñada para el presente estudio, Alfa de Cronbach de 0.96. Los resultados muestran porcentajes bastante elevados de actitudes favorables hacia las conductas adictivas relacionadas con el consumo de sustancias químicas, sexo, ludopatía, desordendes alimenticios, tecnologia, compras, vigorexia y ergomanía, lo cual indica la necesidad de intervenciones psicoeducativas orientadas al fomento de consciencia critico-reflexiva en la poblacion estudiantil al respecto de muchos aspectos relacionados con los valores imperantes en la sociedad contemporanea, con el fin de evitar un posible surgimiento de futuros comportamientos adicitvos en estas áreas de sus vidas.

Este artículo examina la robustez que sostiene el núcleo teórico ortodoxo, más específicamente, los supuestos de información y racionalidad perfectas. Se hace alusión a un modelo de toma de decisiones bajo racionalidad acotada y perfecta información como alternativa teórica.

Background: The financial burden resulting from cancers on families is higher when it arises in young people compared with older adults. Previous research has provided insight into the financial toxicities associated with childhood cancer, but less is known about the efficacy of financial aid systems in reducing the financial burden on families. We conducted a scoping review to identify the determinants of success and failure of financial aid. Methods: Five databases were searched for articles published between January 1, 2000 and December 1, 2022. Dual processes were used to screen and select studies. Through thematic content analysis, we identified barriers and enablers of financial aid, categorised by country income level. Results: From 17 articles, which were evenly split between high-income countries and upper middle- to low-income countries, four major themes emerged: (1) accessibility of support, (2) delivery of support, (3) administration, and (4) psychosocial factors. Within these themes, the enablers identified were (1) support navigators, (2) establishing a direct contact between donors and beneficiaries, (3) implementation of digital solutions to improve outreach, and (4) using cultural and community values to encourage donor engagement. Conclusions: This scoping review identified the determinants of success and failure of financial aid in supporting families in the context of childhood, adolescent, and young adult (CAYA) cancers. By understanding the barriers and enablers identified in this review, organizations could develop pragmatic evidence-based care models and policies to ensure access to assistance is equitable and appropriate for families experiencing CAYA cancers. [ABSTRACT FROM AUTHOR]