Search

Background Despite a rigorous screening process, including cardiac catheterization, a subset of patients with a single right ventricle (SRV) demonstrates suboptimal short‐term outcomes after the Fontan operation. The goal of this study was to perform a comprehensive assessment of diastolic function in pre‐Fontan patients with an SRV using invasive reference‐standard measures and determine their associations with post‐Fontan outcomes. Methods and Results Children aged 2 to 6 years with SRV physiology undergoing pre‐Fontan heart catheterization were recruited prospectively. Patients were divided into those who had an optimal or suboptimal outcome. A suboptimal outcome was defined as length of stay ≥14 days or heart transplant/cardiac death in first year after Fontan. Patients underwent pressure–volume loop analysis using reference‐standard methods. The measure of ventricular stiffness, β, was obtained via preload reduction. Cardiac magnetic resonance imaging for extracellular volume and serum draws for matrix metalloproteinase activity were performed. Of 19 patients with an SRV, 9 (47%) had a suboptimal outcome. Mean age was 4.2±0.7 years. Patients with suboptimal outcomes had lower ventricular stiffness (0.021 [0.009–0.049] versus 0.090 [0.031–0.118] mL−1; P=0.02), lower extracellular volume (25% [28%–32%] versus 31% [28%–33%]; P=0.02), and lower matrix metalloproteinase‐2 (90 [79–104] versus 108 [79–128] ng/mL; P=0.01) compared with patients with optimal outcomes. The only invasive measure that had an association with suboptimal outcome was β (P=0.038). Conclusions Patients with an SRV with suboptimal outcome after the Fontan operation had lower ventricular stiffness and evidence of maladaptive extracellular matrix metabolism compared with patients with optimal outcome. This appears to be a novel phenotype that may have important clinical implications and requires further study.

Abstract Background Co-production of research with communities and stakeholders is recognised as best practice, but despite this, transparent reporting and reflective accounts on co-producing research is lacking. Born in Bradford Age of Wonder (AoW) is a large longitudinal health research project, following the health trajectories of up to 30,000 young people across the Bradford district; moreover, AoW has been entirely co-produced with teachers, parents, and young people. This paper describes the co-production of the Born in Bradford Age of Wonder (AoW) project and shares general reflections on co-production from peer researchers involved in co-producing AoW. Methods A co-operative inquiry (CI) approach was used to gather written reflections on co-production from ten peer researchers (one teacher, one parent, eight young people) involved in co-producing the AoW project. Written reflections were collected and rough “themes” were identified using thematic analysis. Results Four key ‘themes’ were identified: (1) promoting young people’s voice and views (2) identifying impacts of co-production, (3) fostering a collaborative ethos, and (4) suggested improvements to the co-production work in AoW. Peer researchers’ reflections highlighted how co-production can positively impact research projects such as AoW, whilst also holding broader benefits including giving young people a voice, facilitating their personal development, and fostering a collaborative ethos both within AoW and with partner organisations. Suggested improvements to AoW co-production included supporting greater numbers of young people and researchers to engage in co-production, organising more regular sessions, and establishing clearer communication channels. Conclusions Peer researchers’ reflections highlight positive impacts of engaging in co-production, both for research projects (including AoW) and for peer researchers’ personal and professional development. That said, continued efforts are needed in AoW to meet young people’s needs and interests, maintain trusting relationships, and foster sustained growth of co-production efforts within and beyond the AoW project. Evaluation of AoW co-production, along with wider partnership building are key to these efforts.

Purpose: Swallow-related motion of the larynx is most significant in the cranio-caudal directions and of` short duration. Conventional target definition for radical radiation therapy includes coverage of the whole larynx. This study longitudinally examined respiration- and swallow-related laryngeal motions using cine-magnetic resonance imaging. We further analyzed the dosimetry to organs at risk by comparing 3D-conformal radiation therapy (3D-CRT), volumetric modulated arc therapy (VMAT), and intensity modulated radiation therapy (IMRT) techniques. Methods: Fifteen patients with T1-2 N0 glottic squamous cell carcinomas were prospectively recruited for up to 3 cine-MRI scans on the Elekta Unity MR-Linear accelerator, at the beginning, middle, and end of a course of radical radiation therapy. Swallow frequency and motion of the hyoid bone, cricoid and thyroid cartilages, and vocal cords were recorded during swallow and rest. Adapted treatment volumes consisted of gross tumor volume + 0.5-1 cm to a clinical target volume with an additional internal target volume (ITV) for personalized resting-motion. Swallow-related motion was deemed infrequent and was not accounted for in the ITV. We compared radiation therapy plans for 3D-CRT (whole larynx), VMAT (whole larynx), and VMAT and IMRT (ITV for resting motion). Results: Resting- and swallow-related motions were most prominent in the cranio-caudal plane. There were no significant changes in the magnitude of motion over the course of radiation therapy. There was a trend of a progressive reduction in the frequency of swallow. Treatment of partial larynx volumes with intensity modulated methods significantly reduced the dose to carotid arteries, compared with treatment of whole larynx volumes. Robustness analysis demonstrated that when accounting for intrafraction swallow, the total dose delivered to the ITV/planning target volume was maintained at above 95%. Conclusions: Swallow-related motions are infrequent and accounting for resting motion in an ITV is sufficient. VMAT/IMRT techniques that treat more conformal targets can significantly spare critical organs at risk such as the carotid arteries and thyroid gland, potentially reducing the risk of carotid artery stenosis-related complications and other long-term complications.

BackgroundCatatonia has been increasingly associated with mood disorders and is recognized as a specifier in the DSM-5 and DSM-5-TR. The DSM-5-TR recognizes melancholia as a specifier for depressive episodes in major depressive disorder and bipolar disorder. It is characterized by severe anhedonia, lack of reactivity, excessive or delusional guilt, and significant vegetative symptoms. As the conceptualization of melancholia expanded beyond its mood components to include psychomotor disturbances, its overlap with psychomotor symptoms or catatonia becomes evident. This overlap was also described in Kahlbaum’s original literature, where he describes the transition between states of melancholia, mania, and catatonia.MethodCase summary of six patients with major depressive disorder or depressed phase of bipolar disorder who were admitted for severe depression, anhedonia, intense anxiety, psychomotor agitation or retardation, indecisiveness, perseveration, and vegetative symptoms such as poor sleep, appetite, and significant weight loss.ResultsAll patients demonstrated rapid and complete resolution of their mood and psychomotor symptoms, indecisiveness, perseveration, as well as psychosis shortly after administration of lorazepam, with recurrence of the above symptoms upon lorazepam discontinuation and resolution upon resumption, in an on-and-off manner.ConclusionThe present study argues for a closer relationship between melancholia and catatonia based on our case series, historical review, overlap in phenomenology, and response to treatment. We propose provisional [Mahgoub] criteria for patients with severe depression and melancholia. The role of GABA agonists, such as lorazepam, can be explored as an option for patients with treatment-resistant depression who meet these criteria for melancholia.LimitationsAbsence of a standardized, systematic assessment tool and a small sample size.

As electrochemistry continues to gain broader acceptance and use within the organic chemistry community, it is important that advanced undergraduate students are exposed to fundamental and practical knowledge of electrochemical applications for chemical synthesis. Herein, we describe the development of an undergraduate laboratory experience that introduces synthetic and analytical electrochemistry concepts to an advanced organic chemistry class. Experiments focus on the electrooxidative [alpha]-functionalization of carbamates, more generally known as the Shono oxidation, and include cyclic voltammetry analysis of two cyclic carbamates and a constant current bulk electrolysis reaction. The exercise offers students an authentic experience in organic electrochemistry, lays a practical and theoretical foundation for future engagement with concepts in electrochemistry and redox chemistry, and strengthens fundamental organic chemistry skills.

Background Adolescence and transition into adulthood are periods shaping life-long mental health, cardiometabolic risk, and inequalities. However, they are poorly studied and understood. By extending and expanding the Born in Bradford (BiB) cohort study through this period using innovative, co-produced approaches to collect and analyse data, we aim to understand better the interplay of factors that influence health and wellbeing, and inform/evaluate interventions to improve them and reduce inequalities. Protocol BiB Age of Wonder (AoW) is a large, whole city cohort that will capture the contemporary lived experience amongst multi-ethnic adolescents progressing into young adulthood. We will collect repeated data from existing BiB participants and their peers (N~30,000 adolescents). The protocol for the first phase of the quantitative methods, involving survey measurements and health assessments in mainstream secondary schools is described here. We describe the co-production behind these methods, and lessons learned from the first year of data collection.

Bradford is multi-ethnic and one of the most deprived districts in the United Kingdom where around a quarter of children live in low-income families. Born in Bradford (BiB) has followed the lives of 13,776 children born in the district between 2007 and 2011. Children in the birth cohort are now entering adolescence, and the next phase of the research - Age of Wonder (AoW) - will be a whole city cohort capturing the experiences of 30,000 adolescents progressing into young adulthood. This protocol focuses on one component of the AoW programme: qualitative longitudinal research (QLR). The study will gather in depth and detailed accounts from a sub-sample of 100 young people across four major research priorities: personal life; social and community life; growing up with difference, and growing up in Bradford. As well as using traditional qualitative methods such as interviews, focus group discussions, and ethnography, we are adopting innovative creative methods including expressions through art, activism, online and digital content, portraits, and critical events. The process of engaging in and co-producing QLR potentially provides a route to empowering young people to shape the narrative of their own lives as well as informing intervention development.

Ce texte écrit à quatre mains est un témoignage sur les goûts musicaux d’Alain. Le professeur de linguistique, rigoureux et méthodique, était aussi un mélomane averti et un bon accordéoniste. Comme pour faire la distinction entre l’ordre apollinien qui régit la linguistique et l’effusion dionysiaque qui caractérise l’univers des notes, il se métamorphosait en Marcel chaque fois qu’il interprétait sur son instrument les chansons du répertoire français et international. Ce texte retrace non seulement son parcours musical, mais aussi des événements qui ont dû jouer un rôle fondamental dans son éveil à la musique. La première partie parle de ses goûts musicaux, en particulier, de sa passion pour Georges Brassens et Boris Vian. Il y est aussi question de son engouement pour les balades haïtiennes et brésiliennes ainsi que pour la musique classique. La deuxième partie rapporte une prestation du musicien dans le cadre d’un cours sur la chanson.

Born in Bradford (BiB) has followed the lives of 13,776 children born in the district between 2007 and 2011. Children in the birth cohort are now entering adolescence, and the next phase of the research - Age of Wonder (AoW) - will be a whole city cohort capturing the experiences of 30,000 adolescents progressing into young adulthood. This protocol focuses on one component of the AoW programme: qualitative longitudinal research (QLR). The study will gather in depth and detailed accounts from a sub-sample of 100 young people across four major research priorities: personal life; social and community life; growing up with difference, and growing up in Bradford. As well as using traditional qualitative methods such as interviews, focus group discussions, and ethnography, we are adopting innovative creative methods including expressions through art, activism, online and digital content, portraits, and critical events. The process of engaging in and co-producing QLR potentially provides a route to empowering young people to shape the narrative of their own lives as well as informing intervention development.

Subjective social status measures a person’s perception of their social class relative to other people and has theoretically and empirically been positively associated with health and wellbeing. A widely used measure of this construct is the MacArthur Scale of Subjective Social Status, which asks people to report their social status by placing themselves on a ladder which represents the social hierarchy of their society or community; the scale has been used with many different populations across many countries. In this research note, we describe two cases where we encountered unexpected reactions to the MacArthur Scale that we believe highlight (a) the salience of relative social status for people’s wellbeing in contemporary society and (b) the concomitant sensitivities raised by measuring this subjective experience. We discuss the implications of these observations for future research.

Background and purpose: A popular Normal tissue Complication (NTCP) model deployed to predict radiotherapy (RT) toxicity is the Lyman-Burman Kutcher (LKB) model of tissue complication. Despite the LKB model’s popularity, it can suffer from numerical instability and considers only the generalized mean dose (GMD) to an organ. Machine learning (ML) algorithms can potentially offer superior predictive power of the LKB model, and with fewer drawbacks. Here we examine the numerical characteristics and predictive power of the LKB model and compare these with those of ML. Materials and methods: Both an LKB model and ML models were used to predict G2 Xerostomia on patients following RT for head and neck cancer, using the dose volume histogram of parotid glands as the input feature. Model speed, convergence characteristics and predictive power was evaluated on an independent training set. Results: We found that only global optimization algorithms could guarantee a convergent and predictive LKB model. At the same time our results showed that ML models remained unconditionally convergent and predictive, while staying robust to gradient descent optimization. ML models outperform LKB in Brier score and accuracy but compare to LKB in ROC-AUC. Conclusion: We have demonstrated that ML models can quantify NTCP better than or as well as LKB models, even for a toxicity that the LKB model is particularly well suited to predict. ML models can offer this performance while offering fundamental advantages in model convergence, speed, and flexibility, and so could offer an alternative to the LKB model that could potentially be used in clinical RT planning decisions.

Organic electrosynthesis is an increasingly popular tool for driving and probing redox reactions. Recent advances in this field often employ an electrocatalyst to enhance the selectivity and efficiency of electrochemical reactions. A laboratory experiment was developed to introduce students to relevant mechanistic techniques in electrochemistry for analysis of electrocatalytic reactions using aminoxyl-catalyzed alcohol oxidation as a case study. This lab activity employs cyclic voltammetry for qualitative assessment of catalytic turnover prior to introducing students to chronoamperometry, an underutilized technique that facilitates quantitative determination of the rate of catalysis. Students identify and rationalize the important features of a reversible electron transfer and a catalytic reaction in a cyclic voltammogram, probe the origin of scan rate effects on these traces, and calculate turnover frequency using a series of chronoamperograms. The method employs safe and readily available reagents: basic aqueous buffer solution, alcohol substrate, and an inexpensive organic aminoxyl catalyst. Student data presented herein were obtained from a course attended by undergraduate students, graduate students, and pharmaceutical chemists.

Background: This case explores the challenges encountered in managing treatment-resistant paranoid schizophrenia, focusing on the limitations of using clozapine due to the risk of neutropenia. The United Kingdom Clozapine Patient Monitoring Service (UK CPMS) and its eligibility criteria are discussed, highlighting the potential benefits of expanding access to clozapine for patients who could potentially benefit from this medication. The integration of clozapine genetic testing as a personalized approach is explored, emphasizing the importance of identifying patients with a favorable genetic profile for clozapine response. Methods: Case report. Results: The case presentation of Mr. X exemplifies the difficulties faced in managing treatment-resistant schizophrenia when access to clozapine is restricted, leading to persistent negative symptoms. Conclusion: The article underscores the importance of innovative solutions and personalized care to enhance the treatment outcomes for patients with treatment-resistant paranoid schizophrenia. It acknowledges that certain restrictions of clozapine use may limit the effective management of patients with this condition. [ABSTRACT FROM AUTHOR]

The travel journal, collecting, and exhibition of objects by museum founder, tea merchant and Member of Parliament Frederick Horniman (1835-1906) in the late nineteenth century demonstrate how material objects exemplify travel writing. Through an examination of objects he collected and later interpreted at the Horniman Free Museum, this article presents a case study of how collecting activities mirror and serve as a form of travel writing. This article presents a new model for understanding, beyond the written word, how travelers can capture the experience of a foreign expedition through the collecting and interpretation of objects. Keywords: museum, museum collecting, nineteenth century, travel writing, Frederick Horniman, India, In part fourteen of his twenty-one-part series 'Through 'The Horniman Museum'' Henry Woolhouse, writing as A. Visitor, notes two models of the Taj Mahal in the museum's Second Indian and [...]