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Preprocedural coronary computed tomography angiography (CCTA) can be useful in procedural planning for chronic total occlusion (CTO) percutaneous coronary intervention (PCI).We examined the clinical, angiographic and procedural characteristics and outcomes of cases with vs. without preprocedural CCTA in PROGRESS-CTO (NCT02061436). Multivariable logistic regression was used to adjust for confounding factors.Of 7034 CTO PCI cases, preprocedural CCTA was used in 375 (5.3%) with increasing frequency over time. Patients with preprocedural CCTA had a higher prevalence of prior coronary artery bypass graft surgery (39% vs. 27%, p 0.001) and angiographically unfavorable characteristics including higher prevalence of proximal cap ambiguity (52% vs. 33%, p 0.001) and moderate/severe calcification (59% vs. 41%, p 0.001) compared with those without CCTA. CCTA helped resolve proximal cap ambiguity in 27%, identified significant calcium not seen on diagnostic angiography in 18%, changed estimated CTO length by5 mm in 10%, and was performed as part of initial coronary artery disease work up in 19%. CCTA cases had higher J-CTO (2.6 ± 1.2 vs. 2.3 ± 1.3, p 0.001) and PROGRESS-CTO (1.3 ± 1.0 vs. 1.2 ± 1.0 p = 0.027) scores. After adjusting for potential confounders, cases with preprocedural CCTA had similar technical success (odds ratio [OR]: 1.18, 95% confidence interval [CI], 0.83-1.67) and incidence of major adverse cardiovascular events (OR: 1.47, 95% CI, 0.72-3.00).Preprocedural CCTA was used in ~5% of CTO PCI cases. While CCTA may help with procedural planning, especially in complex cases, technical success and MACE were similar with or without CCTA.

Bispecific T-cell engager (BiTE) molecules have great potential to treat cancer. Nevertheless, dependent on the targeted tumor antigen, the mechanism of action that drives efficacy may also contribute to on-target/off-tumor toxicities. In this study, we characterize an anti-CD70 half-life extended BiTE molecule (termed N6P) which targets CD70, a TNF family protein detected in several cancers. First, the therapeutic potential of N6P was demonstrated using in vitro cytotoxicity assays and an orthotopic xenograft mouse study resulting in potent killing of CD70+ cancer cells. Next, in vitro characterization demonstrated specificity for CD70 and equipotent activity against human and cynomolgus monkey CD70+ cells. To understand the potential for on-target toxicity, a tissue expression analysis was performed and indicated CD70 is primarily restricted to lymphocytes in normal healthy tissues and cells. Therefore, no on-target toxicity was expected to be associated with N6P. However, in a repeat-dose toxicology study using cynomolgus monkeys, adverse N6P-mediated inflammation was identified in multiple tissues frequently involving the mesothelium and epithelium. Follow-up immunohistochemistry analysis revealed CD70 expression in mesothelial and epithelial cells in some tissues with N6P-mediated injury, but not in control tissues or those without injury. Collectively, the data indicate that for some target antigens such as CD70, BiTE molecules may exhibit activity in tissues with very low antigen expression or the antigen may be upregulated under stress enabling molecule activity. This work illustrates how a thorough understanding of expression and upregulation is needed to fully address putative liabilities associated with on-target/off-tumor activity of CD3 bispecific molecules.

The prevalence and outcomes of patients who presented with an acute coronary syndrome (ACS) and underwent chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study.We examined the clinical characteristics and procedural outcomes of ACS patients who underwent CTO-PCI in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO; NCT02061436).Of the 8826 patients who underwent CTO-PCI between 2012 and 2022 at 38 centers, 558 (6.3%) presented with ACS. ACS presentation was with non-ST-segment elevation myocardial infarction (MI) in 54%, unstable angina in 33%, and ST-segment elevation MI in 6.5%. ACS patients were older (66 ± 11 years vs 64 ± 10 years; P.001) and had higher prevalence of comorbidities such as diabetes mellitus (48% vs 42%; P=.02), prior MI (52% vs 45%; P.01), and lower left ventricular ejection fraction (49 ± 14% vs 51 ± 13%; P.01). While the PROGRESS-CTO score (1.4 ± 1.0 vs 1.2 ± 1.0; P.001) was higher in the ACS group, the J-CTO score was comparable (2.3 ± 1.2 vs 2.4 ± 1.3; P=.68). Technical success (88% vs 86%; P=.12) and the incidence of in-hospital major adverse cardiovascular event (MACE) (0.9% vs 2.1%; P=.06) and adverse events at 3-month follow-up (3.4% vs 7.2%; Kaplan-Meier log-rank P=.16) were similar between ACS and non-ACS patients, respectively.Approximately 6% of patients who underwent CTO-PCI presented with an ACS. Technical success, in-hospital MACE, and the incidence of adverse events up to 3 months were similar between patients who presented with vs without an ACS.

BACKGROUND Research on problematic internet use has largely adhered to addiction paradigms, possibly impeding the identification of specific internet behaviors related to psychopathology. This study presents a novel approach to screening for specific problematic internet behaviors by using a new measure, the emergency department media use screener (EDMUS). OBJECTIVE The purpose of this study was to identify patterns of internet use in young people presenting with mental health concerns to the emergency department (ED), ascertain associations with their mental health, and evaluate whether the EDMUS can be used to predict subsequent ED presentations within 3 months. METHODS This cross-sectional retrospective study of Australian young people (N=149, aged 11-25 years; female: n=92, 61.7%) sought to use the EDMUS, a 24-item questionnaire, to identify problematic internet behaviors, including accessing or posting prosuicidal or proeating disorder content, cyberbullying, and inappropriate digital content. Data on each person’s mental health were extracted from electronic medical records to look for associations with EDMUS responses and ED re-presentation over 3 months. EDMUS items were grouped into clusters for analysis using chi-square tests, binary logistic regression, and path analyses. RESULTS Sharing suicidal digital content was the most common problematic internet use pattern identified by the EDMUS. However, this did not correlate with having a prior mental health diagnosis or predict readmission. Most participants had families with a concern for their internet use; however, this was less likely in participants with a diagnosis of personality disorder. Diagnoses of personality disorder or posttraumatic stress disorder were independent predictors of readmission (P=.003; P=.048). CONCLUSIONS Although a history of complex psychopathology increases the likelihood of subsequent ED presentations, its links to internet use–related behaviors are still unclear. The EDMUS has potential for identifying young people who are most vulnerable to problematic internet behaviors and offers the opportunity for early intervention and potential prevention of more entrenched difficulties.

Taking as my starting point Almodovar’s statement that Los abrazos rotos contains ‘una historia que subyace a todas las demas’ and building upon Javier Herrera’s attention to the ‘doubling’ within the film, together with Maria Delgado’s and Katarzyna Beilin’s claims that it can be linked to questions of historical memory, in this article I will examine in greater detail Almodovar’s comments regarding the influence of Lanzarote and the prominent Lanzarotean artist/sculptor Cesar Manrique on this film. After analysing the scenes that take place on the island and assessing their relevance to the film as a whole, I contend that Lanzarote is a prime force and, furthermore, that Los abrazos rotos contains strong links with the work, life and death of Manrique, whom Almodovar met during his visit to the island in 1986. Finally, I propose that it is through exploring the significance of Lanzarote and Manrique in this complex, multi-layered film that we can fully appreciate Almodovar’s engagement with contemporary Spanish issues in Los abrazos rotos and the way in which he uses the film to raise provocative questions about Spain’s present, past and future, the status and role of the Hispanic periphery and the construction of utopias.

An upfront (primary) retrograde strategy is often used in complex chronic total occlusion (CTO) percutaneous coronary intervention (PCI).We examined the clinical, angiographic characteristics, and procedural outcomes of CTO PCIs that were approached with a primary retrograde strategy in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO, NCT02061436).Of 10,286 CTO PCIs performed between 2012 and 2022, a primary retrograde strategy was used in 1329 (13%) with an initial technical success of 66%, and a final success of 83%. Patients who underwent successful versus unsuccessful primary retrograde cases had similar characteristics: age (65 ± 10 vs. 65 ± 9, years, p = 0.203), men (83% vs. 87%, p = 0.066), prior PCI (71% vs. 71%, p = 0.809), and prior coronary artery bypass graft surgery (52% vs. 53%, p = 0.682). The PROGRESS-CTO score (1.3 ± 0.9 vs. 1.6 ± 0.9, p 0.001), air kerma radiation (3.9 ± 2.8 vs. 3.4 ± 2.6, gray, p = 0.013), and contrast use (294 ± 148 ml vs. 248 ± 128, ml, p 0.001) were higher in the unsuccessful group, whereas the presence of interventional collaterals (95% vs. 72%, p 0.001) and Werner collateral connection grade 2 (43% vs. 31%, p 0.001) were higher in the successful group. On multivariable logistic regression analysis, the only variable associated with a successful primary retrograde strategy was the presence of interventional collaterals: odds ratio: 6.52 (95% confidence intervals; 3.5-12.1, p 0.001).Presence of interventional collaterals is independently associated with higher success rates with a primary retrograde strategy in CTO PCI.

Glucose-dependent insulinotropic polypeptide receptor (Gipr) gene expression has been reported in mouse spermatids and Gipr knockout male mice have previously been reported to have decreased in vitro fertilization, although the role of Gipr signaling in male mouse fertility is not well understood.The purposes of these studies were to determine the role of glucose-dependent insulinotropic polypeptide receptor in male fertility using Gipr knockout mice and anti-glucose-dependent insulinotropic polypeptide receptor antibody-treated wild-type mice and to determine if the expression of Gipr in mouse testes is similar in non-human and human primates.Adiponectin promoter-driven Gipr knockout male mice (GiprGiprThe infertility of GiprOur data support a role for Gipr expression in the mouse testis during the development of sperm fertilization potential, but based on gene expression data, a similar role for glucose-dependent insulinotropic polypeptide receptor in non-human primate or human male fertility is unlikely.

The prevalence, treatment, and outcomes of balloon undilatable lesions encountered in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study.We examined the clinical characteristics and procedural outcomes of balloon undilatable lesions in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO, NCT02061436).Of 6535 CTO PCIs performed between 2012 and 2022, 558 (8.5%) lesions were balloon undilatable. In this subset, patients were older (mean age 67 ± 10 vs. 64 ± 10, p 0.001) and had higher prevalence of comorbidities: diabetes mellitus (54% vs. 40%, p 0.001), prior PCI (71% vs. 59%, p 0.001), prior myocardial infarction (52% vs. 45%, p = 0.003), and prior coronary artery bypass graft surgery (44% vs. 25%, p 0.001). The CTO lesion length was estimated to be 34 ± 23 mm, mean J-CTO score was 2.9 ± 1.1 and mean PROGRESS-CTO score was 1.4 ± 1.0. A cutting balloon was used in 27%, a scoring balloon in 15%, laser in 14%, rotational atherectomy in 28%, orbital atherectomy in 10%, intravascular lithotripsy in 1% and other modalities/approaches in 5%. Balloon undilatable lesions had lower technical success (90.9% vs. 93.8%, p = 0.007) and higher incidence of major adverse cardiovascular events (MACE) (composite of in-hospital death, acute myocardial infarction, stroke, re-PCI, emergency CABG, and pericardiocentesis) (5.0% versus 1.3%, p 0.001).Approximately 1 in 12 CTO (8.5%) lesions are balloon undilatable. Treatment of balloon undilatable lesions is associated with lower technical success and higher in-hospital MACE.

Background: The relationship between left ventricular ejection fraction (LVEF) and the success and safety of coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. Methods: We examined the clinical characteristics and outcomes of CTO PCI in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO) after stratifying patients by LVEF (≤35%, 36%–49%, and ≥50%). Results: A total of 7827 CTO PCI procedures with LVEF data were included. Mean age was 64 ± 10 years, 81% were men, 43% had diabetes mellitus, 61% had prior PCI, 45% had prior myocardial infarction, and 29% had prior coronary artery bypass graft surgery. Technical success was similar in the three LVEF strata: 85%, 86%, and 87%, p = 0.391 for LVEF ≤35%, 36%–49%, and ≥50%, respectively. In-hospital mortality was higher in lower LVEF patients (1.1%, 0.4%, and 0.3%, respectively, p = 0.001). In-hospital major adverse cardiovascular events (MACE) were numerically higher in lower EF patients (2.7%, 2.1%, and 1.9%, p = 0.271). At a median follow-up of 2 months (interquartile range: 19-350 days), patients with lower LVEF continued to have higher mortality (4.9%, 3.2%, and 1.4%, p < 0.001) while the MACE rates were similar (9.3%, 9.6%, and 7.4%, p = 0.172). Conclusion: CTO PCI can be performed with high technical success in patients with reduced LVEF but is associated with higher in-hospital and post-discharge mortality.

espanolPartiendo de la premisa de que el profundo interees de Galdos en el espacio merece maas atencion academica, este artiiculo analiza su significado en Torquemada en la hoguera. Empieza por examinar la relacion entre los lugares que aparecen en la novela y el mundo real, y propone que el autor codifica la ciudad de Madrid para comunicar sus preocupaciones sociales y captar la atencion de los lectores. Procede a analizar el significado de la esfera publica, junto con la privada, antes de destacar la importancia de la imaginacion en la novela. Revela que para Galdos, al igual que en sus articulos periodisticos, en Torquemada en la hoguera la realidad sirve como trampolin imaginativo, y que los sitios desencadenan lo que es efectivamente un “espacio de pensamiento” para el autor. Cuando desentra~namos su significado, los lectores llegamos a apreciar mas cabalmente la sensibilidad psicologica de Galdos, la modernidad de esta novela, su valor simbolico y su profundidad imaginativa. El articulo concluye proponiendo que las obras de Galdos merecen ser reexaminadas como “Novelas de la imaginacion geografica” e insta a los lectores a reexaminar el significado del espacio y de los sitios que aparecen en ellas. EnglishDeparting from the premise that Galdos’s close engagement with space and place deserves to be at the forefront of scholarly attention, this article provides an in-depth study of their significance in Torquemada en la hoguera. It begins by analysing the relationship between the novel’s locations and the real world, demonstrating that the author codes the city of Madrid to express social concerns and promote reader engagement. It then proceeds to examine the public and private spheres, before highlighting the “place of the imagination” in the novel. It reveals that, as in Galdos’s press articles, reality is used as a springboard in Torquemada en la hoguera and, drawing upon recent theories, it posits that places serve as a framework for engaging readers with contemporary concerns and as an imaginative springboard for Galdos. They trigger what is effectively a “thinking space” for the author and it is through unravelling their significance that we can fully appreciate Galdos’s psychological sensitivity, the novel’s modernity, its symbolic value, and imaginative depth. The article concludes by proposing that Galdos’s works deserve to be reexamined as “Novels of the Geographical Imagination” and urges readers to revisit the significance of space and place therein.

The aim of this article is threefold: to call for a reassessment of Canarian literature and the novela negra, both of which have been undervalued to date, and to accord critical attention to the talented Lanzarotean author, Miguel Aguerralde. It sets out to fulfil this via the first close study of Claro de Luna, examining the ways Aguerralde employs the novela negra framework and other narrative devices to engage readers with the interconnected themes of identity, solitude and place. It demonstrates that in this complex, multi-layered novel, the narrative technique is used to subvert expectations and the choice of setting, the use of cultural allusiveness, together with the presentation of authority and gender can be related to questions concerning “a sense of place”, the “decentring” of Peninsular Spain to focus on the Canary Islands. Simultaneously, Claro de Luna transcends the specificity of its setting and the limitations of the novela negra by ambitiously tackling questions of universal relevance, exploring identity in relation to mental health and stability and interrogating the nebulous notions of fantasy and “the abnormal”. In-so-doing, Aguerralde questions the validity of objective constructs such as identity vis a vis subjective perceptions and poses questions about the islands’ future.

This article is the first detailed study of Miguel Aguerralde’s Canarian novel, Noctámbulo. It explores the way in which the author revitalizes vampire traditions, submerging his vampire protagonist, who is transformed into a paid assassin, into the seemingly incongruous environment of Gran Canaria. Challenging and subverting expectations, and offering readers the opportunity to regard its Canarian vampire protagonist as a Robin Hoodesque hero, Noctámbulo incites us to reflect profoundly on matters pertaining to the specific Canarian context (particularly the islands’ status as ‘the outcast’ in relation to mainland Spain, issues concerning memory and grappling with the past), as well as on broader concerns. The article concludes by postulating that Noctámbulo is a liberating transnational novel, one which transcends genres and borders, refutes preconceived ideas and offers readers worldwide the opportunity to determine how they will interpret the work and envision their futures.

Sotorasib (Lumakras™) is a first-in-class, non-genotoxic, small molecule inhibitor of KRAS G12C developed as an anticancer therapeutic for treatment of patients that have a high unmet medical need. Anticancer therapeutics are considered out of scope of ICH M7 guidance for control of mutagenic impurities; however, based on ICH S9 QA, mutagenicity assessments are needed for impurities that exceed the qualification threshold, consistent with ICH Q3A/B, and non-mutagenic drugs. Here, we carried out hybrid-based mutagenicity assessment of sotorasib drug substance (DS) impurities using in silico quantitative structure-activity relationship (QSAR) modelling and Ames tests (for in silico positive mutagens). We encountered contradictive mutagenicity results for 2 impurities (Beta-Chloride and PAC). PAC was negative initially by QSAR but positive in a GLP full plate Ames test and Beta-Chloride was positive by QSAR, negative in a non-GLP micro-Ames but positive in a GLP full plate Ames assay. Root cause analyses identified and characterized mutagenic contaminants, 3-chloropropionic acid in batches of Beta-Chloride and 3-chloropropionic acid and Chloro-PAC in batches of PAC, used in initial GLP full-plate Ames tests. Significant reduction of these contaminants in re-purified batches resulted in no induction of mutagenicity in follow-up GLP micro-Ames tests. In summary, root-cause analyses led to accurate mutagenicity assessment for sotorasib DS-associated impurities.

INTRODUCTION Glioblastoma (GBM) is the most aggressive primary brain tumour in adults, leading to universal recurrence despite aggressive surgical and chemotherapeutic treatment. Post-recurrence, median overall survival is 6 to 10 months and treatment options are very limited. One of the biggest challenges in treating GBM is achieving high local drug concentration; systemic administration of cytotoxic agents has failed in the past due to this limitation. Convection enhanced delivery (CED) is a ‘direct-to-brain’ drug delivery method that previously demonstrated its usefulness in overcoming this challenge. MTX110 (Midatech Pharma Ltd) is a water-soluble form of panobinostat, that demonstrated cytotoxic activity in 4 GBM cell lines (U87MG, U251MG, U118MG and T98G) with an average IC50 value around 40nM which also translated into pre clinical in vivo efficacy, in combination with radiotherapy1. Delivery of MTX110 via an implanted pump and CED catheter system in patients with GBM appears to be an attractive treatment option, that allows for therapeutic doses of the drug to be delivered weekly directly to the tumour, thus avoiding systemic administration and therefore toxicity. This has previously been demonstrated in investigator-initiated studies of paediatric patients with diffuse intrinsic pontine glioma. METHOD MAGIC-G1 study is a Phase 1 two-cohort dose-escalating study that will assess safety and feasibility of intermittent intratumoral administration of MTX110 by CED to rGBM patients; either as a single agent (Cohort 1) or in combination with lomustine (Cohort 2). Eligible patients will have a catheter system and an abdominal refillable pump implanted in an aseptic manner, with the tip of the catheter positioned stereotactically at the centre of the tumour. 48-hour infusions will be administered weekly until disease progression and doses of 30, 60 and 90 mM will be investigated. Cohort 1 recruitment will be completed before Cohort 2 starts dosing. Study results are expected in 2023.

Sotorasib is a first-in-class KRAS

Calcitonin gene-related peptide (CGRP) and its receptor have been implicated as a key mediator in the pathophysiology of migraine. Thus, erenumab, a monoclonal antibody antagonist of the CGRP receptor, administered as a once monthly dose of 70 or 140 mg has been approved for the preventive treatment of migraine in adults. Due to the species specificity of erenumab, the cynomolgus monkey was used in the pharmacology, pharmacokinetics, and toxicology studies to support the clinical program. There were no effects of erenumab on platelets in vitro (by binding, activation or phagocytosis assays). Specific staining of human tissues with erenumab did not indicated any off-target binding. There were no erenumab-related findings in a cardiovascular safety pharmacology study in cynomolgus monkeys or in vitro in human isolated coronary arteries. Repeat-dose toxicology studies conducted in cynomolgus monkeys at dose levels up to 225 mg/kg (1 month) or up to 150 mg/kg (up to 6 months) with twice weekly subcutaneous (SC) doses showed no evidence of erenumab-mediated adverse toxicity. There were no effects on pregnancy, embryo-fetal or postnatal growth and development in an enhanced pre-postnatal development study in the cynomolgus monkey. There was evidence of placental transfer of erenumab based on measurable serum concentrations in the infants up to 3 months post birth. The maternal and developmental no-observed-effect level (NOEL) was the highest dose tested (50 mg/kg SC Q2W). These nonclinical data in total indicate no safety signal of concern to date and provide adequate margins of exposure between the observed safe doses in animals and clinical dose levels.

Sotorasib is a first-in class KRAS

INTRODUCTION Panobinostat is a histone deacetylase (HDAC) inhibitor with antineoplastic and anti-angiogenic effects in glioma. HDAC inhibitors have demonstrated therapeutic efficacy preclinically via multiple mechanisms, including the induction of cell-cycle arrest, differentiation, senescence, apoptosis, mitotic cell death, autophagy, generation of reactive oxygen species, inhibition of angiogenesis and metastasis, and improvement in tumor immunity. One of the biggest challenges in treating glioblastoma is achieving effective local drug concentrations, and trials using systemic administration of therapeutics have failed in GBM despite compelling pre clinical evidence. MTX110 (Midatech Pharma plc) is a water-soluble form of panobinostat currently in clinical development for DIPG and medulloblastoma using direct tumour delivery. We explored the therapeutic potential of MTX110 in GBM in our preclinical in vivo adult brain tumor models. METHODS Tumor-bearing mice were stratified to either the vehicle control or treatment group based on median tumor volume and were treated with Panobinostat/MTX110 at a dose of 15mg/kg IP, twice weekly for 5 consecutive weeks. The response to treatment was assessed by delay in tumor growth in days, expressed as a T (Treated) - C (Control) value. Statistical analysis was performed using SAS (a statistical analysis program) and the Wilcoxon rank order test. RESULTS MTX110 produced non-significant growth delays of 10.76 and 2.01 days (p Value ≥ 0.072 NS) in IDH wild type xenograft lines. However, in an IDH1 mutated line, MTX110 produced a significant growth delay of 23.35 days (p Value ≤ 0.018). Further work is ongoing to look at the therapeutic potential of MTX110 in combination with radiation in both IDH wild type and IDH mutated xenograft lines.

Throughout the nineteenth century, the Spanish press, aiming to appeal to a wider audience, adopted a more sensationalist flavour and sought to satiate the public’s fascination with crime. This article traces the development of the relationship between crime and the press through the initiatives of the Madrilenian cultural review La Espana Moderna, whose general editor, Jose Lazaro Galdiano, rather than pandering to the public’s demands for sensationalist descriptions, decided to use his publication as a forum for discussions on the topic and to publish articles both on, and by some of the leading criminologists of the period. Lazaro and the contributors of La Espana Moderna innovatively sought not only to educate the public on the latest ideas on crime and criminology but also, through the vehicle of literature and other techniques, to make these new currents of thought accessible to a wider public. They encouraged readers to situate their own ideas within the context of European debates, notably those relating to questions surrounding Spain’s racial inferiority and degeneration. In so doing, the review aimed to incite interest in the topics of crime and criminology, to open up new discussions, to promote reform and thereby facilitate Spain’s regeneration.

In his 1950 film adaptation of Galdos’s 1876 novel Dona Perfecta the Mexican director Alejandro Galindo transferred the action from the imaginary Spanish city of Orbajosa to Santa Fe in Mexico. To date critics have focussed largely upon assessing the ‘Mexicanism’ of the film, coming to the conclusion that the film, like the novel, is an overblown melodrama. This article will now pay close attention to the artistic qualities of the film, specifically its use of space and place, and will seek to demonstrate how Galindo, responding as a reader of Galdos’s novel, produces a work that not only invites new ways of reading Dona Perfecta but also highlights its timelessness and universality.

Considered superficially, the women in the Torquemada novels conform to the negative gender stereotypes imposed upon them by their male counterparts. On further examination, however, we discover th...

Building upon James Whiston’s studies on Galdos’ dedication to the correction of his manuscripts and his preoccupation with contemporary matters, this article sets out to explore the novelist’s hitherto largely overlooked attention to language, and particularly its effectiveness in his work as a vehicle for communication. The article highlights Galdos’ concern with the superficiality of language employed in the oratorical sphere and examines why his style was undervalued during his lifetime. Using Torquemada en la hoguera as a case study, the article then proceeds to explore the different styles and the significance of individual words within this novel. Revealing that words can be used to deceive others, and additionally lead to misunderstandings, this study moves on to highlight Galdos’ sensitivity to non-verbal communication and examines the way that he innovatively employs body language. Torquemada en la hoguera is shown to reveal the author’s dissatisfaction with the superficiality of fin de siglo society, its propensity for imitation and the major problems it has in communication; the novel is seen also to expose the challenge faced by Realist writers attempting to use words to reproduce life. Finally, this article contends that Galdos uses language in Torquemada en la hoguera (and other novels) to incite readers to engage in a process of self-regeneration.

The late nineteenth century saw a new seriousness of purpose accorded to the novel as a steady flow of works increasingly engaged with pressing questions relating to Spain’s future amidst the overr...

This newsletter aims to provide an overview of the currently available evidence pertaining to the benefits and risks of oral antiplatelet therapies, with a focus on balancing ischemic and bleeding risk to optimize patient outcomes.