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Background: Anti-CD20 monoclonal antibodies are highly effective for RMS treatment. Ocrelizumab (OCR) is standard, while Rituximab (RTX) is an alternative. The impact of anti-CD20 therapies on immune markers remains understudied, though deficiencies are frequently observed and have been associated with increased risk of infection. Our objective is to characterize and compare lymphocyte, neutrophil, and immunoglobulin levels in OCR- versus RTX-treated persons with RMS. Methods: This retrospective chart review included RMS patients on OCR or RTX (2017–2023). Pre- and post-treatment levels of lymphocytes, neutrophils, and immunoglobulins (IgG, IgA, IgM) were analyzed. Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models were used for survival analysis. Results: 350 patients (OCR=175, RTX=175) were included. The mean treatment length was 60.9 (SD 19.1) months for OCR and 42.7 (SD 19.5) months for RTX. RTX was associated with a significantly shorter time to IgM deficiency (29.6 vs. 40.0 months, p=0.02). Cox analysis confirmed RTX increased IgM deficiency risk (HR=1.54, 95% CI: 1.06-2.23, p=0.02). No differences were seen for lymphocytes, neutrophils, IgG, or IgA. Conclusions: RTX was associated with a shorter time to and increased risk of IgM hypogammaglobulinemia compared to OCR, highlighting the importance of long-term monitoring. Further research is needed to guide treatment decisions.
Despite its many extensions and implications, we argue that punctuated equilibrium itself has two core, empirical claims: (1) stasis dominates within fossil species; and (2) morphological change is concentrated in pulses that occur associated with speciation. Here we assess the state of the evidence for these two claims, 50 years after punctuated equilibrium’s foundational paper. Spurred by controversy, paleontologists have amassed a large number of case studies in which morphology in species-level lineages is tracked over time. Modern, likelihood-based methods have been used to fit to these data models of stasis, random walks, and directional trends, as well as more complex dynamics. Compilations reveal that the directional trends predicted by gradualist expectations are infrequent. Although stasis is commonly observed, it is favored in less than half of cases, and meandering random walks or more complex models generally account for the majority of cases. The second claim of punctuated equilibrium has received much less empirical scrutiny than the first. Although speciational pulses are plausible in theory, only a few paleontological studies integrate ancestor–descendant time series into a phylogenetic framework as is needed to estimate cladogenetic change and compare it with anagenesis. These studies, as well as more indirect analyses of extant clades, suggest that speciational change can occur, but we cannot yet assess with confidence its frequency or importance compared with anagenetic changes.
This paper reviews efforts to meet the climate goals of the Paris Agreement: to limit global warming to well below 2°C and ideally to 1.5°C above pre-industrial levels. The paper shows how the likelihood of breaching these thresholds presents the need for additional measures, in mitigation and intervention. Three climate actions are discussed: emissions reduction, greenhouse gas removal, and solar radiation modification. These actions differ in timescale and current state of knowledge. Progress must intensify if they are to aid in securing a safe and stable climate for future generations.
Technical summary
Current assessments of global greenhouse gas emissions suggest the Paris Agreement temperature thresholds of 1.5°C and 2°C warming above pre-industrial levels could be breached. The impacts on humans and ecosystems could be severe. Global trends suggest a prolonged reliance on fossil fuels. Additional measures to limit global warming are therefore needed. Here, we review three climate actions: emissions reduction, greenhouse gas removal (GGR), and solar radiation modification (SRM). Emissions reduction requires shifting energy production away from fossil fuels (the primary contribution of anthropogenic greenhouse gas emissions), reducing energy use in key sectors, and optimising land management. GGR efforts must scale sustainably in the near term. The scale-up of novel methods is constrained by economic and technological challenges and, in some cases, limited knowledge. SRM has received growing attention, given the immediate impacts of global warming and the protracted timescales of emissions reduction and GGR. Robust research and governance frameworks are needed to assess the risks posed by SRM, alongside the risks of forgoing SRM. These three actions could enable society to fulfil the Paris Agreement, limiting global warming and its impacts while atmospheric greenhouse gas concentrations are reduced to sustainable levels.
Social media summary
The progress of climate mitigation and intervention towards securing a sustainable future in a safe and stable climate.
Uterine inversion is a rare though life-threatening complication of childbirth, often accompanied by hemorrhage and hypovolemic shock with associated morbidity. Risks include fundal placenta, placenta accreta spectrum, short umbilical cord, atony, maternal factors such as connective tissue disorders, uterine tumors or structural abnormalities, and congenital weakness of the uterine wall. The diagnosis is clinical, and mainstays of treatment involve prompt recognition and quick action. The focus of treatment is manual reduction, which may require tocolytics. In rare instances when manual reduction is not successful at the bedside, laparotomy may become necessary. Additional care involves uterine massage, uterotonics, and hemorrhage management.
Recent studies applying William Caplin’s form-functional theory to Richard Wagner’s music have focused on Das Rheingold and later music dramas. However, his earlier Lohengrin, the final work he titled ‘romantische Oper’, proves an ideal candidate for such a study, since it still retains certain conventions (such as subtly disguised ‘numbers’ and a fairly clear harmonic palette) while pushing the boundary on others (such as scenes built as ‘dialogue cycles’ and pervasive use of diminished-seventh harmonies). This study first focuses on the principal Leitmotivs of the work, those associated with Elsa, Ortrud, the Grail and the Frageverbot (forbidden question), examining their theme types and loosening features, then exploring their transformations in different appearances throughout the opera – particularly Elsa’s motive. It then considers selected passages constructed in ‘rotational form’, in which one or more of these leitmotivs are used as the backbone for the cyclic form.
There are 117.3 million people forcibly displaced because of war, conflict and natural disasters: 40% are children. With growing numbers, many high-income countries have adopted or are considering increasingly restrictive policies of immigration detention. Research on the impact of detention on mental health has focused on adults, although recent studies report on children.
Aims
To synthesise data on the impact of immigration detention on children’s mental health.
Method
Systematic searches were conducted in PsycINFO, MEDLINE and Embase databases and grey literature and studies assessed using PRISMA guidelines (PROSPERO registration CRD42023369680). Included studies were quantitative, assessed children younger than 18 years who had been in immigration detention and reported mental health symptoms or diagnoses. Methodological quality was assessed using the Appraisal Tool for Cross-Sectional Studies. Meta-analyses estimated prevalence for major depression and post-traumatic stress disorder (PTSD).
Results
Twenty-one studies reported data on 9620 children. Most studies were cross-sectional, had small sample sizes and used convenience sampling. A profoundly detrimental impact on children’s mental health across a variety of countries and detention settings was demonstrated. Meta-analysis found pooled prevalence of 42.2% for depression [95% CI 22.9, 64.3] and 32.0% for PTSD [95% CI 19.4, 48.0]. Severity of mental health impact increased with exposure to indefinite or protracted held detention.
Conclusions
Immigration detention harms children. No period of detention can be deemed safe, as all immigration detention is associated with adverse impacts on mental health. Our review highlights the urgency of alternative immigration policies that end the practice of detaining children and families.
Chapter 3 traces the history of bowing at the name of Jesus, one of the ritual actions inherited from the medieval church which survived into the post-Reformation period. Although it was included in the 1559 Injunctions, most Elizabethan writers regarded it as a matter of indifference and assumed it would gradually die out of its own accord. Yet in the early seventeenth century it unexpectedly resurfaced as a point of theological debate when some divines argued that it was directly commanded by scripture. The chapter challenges the idea that theological controversy was conducted at a high academic level with little relevance to the lives of ordinary people. The dispute over bowing originated in polemical exchanges between Protestants and Catholics in Westphalia, which were taken up by the Reformed theologian David Pareus at Heidelberg, and then spilled over into the Church of England when Pareus’s writings were translated into English. But while it began in Latin works of religious polemic, it also led to conflict at a parish level, and a study of these parish conflicts shows that the lay opponents of bowing were often very well informed about the theological issues.
Chapter 4 discusses the sign of the cross, another gesture with a long history going back to the early church. In the Middle Ages the cross was believed to have power to protect against evil, and was widely used both as a gesture of everyday blessing and in rituals and charms of healing. After the Reformation its use was discouraged, but it survived in the Prayer Book rite of baptism, where the minister was instructed to trace a cross on the child’s forehead. This necessitated a radical transformation in its meaning, removing the associations with exorcism and purification and redefining it simply as a symbol of allegiance to Christ. Yet the belief in the apotropaic power of the cross persisted in early modern England and was reflected both officially, in the ritual of the royal touch, and unofficially, in the use of the gesture as a form of protection against witchcraft. Even among theologians who regarded the cross as symbolic, there was still a sense that it was not ‘merely’ symbolic but retained some kind of operative power to effect change.
The conclusion traces a history of religious gesture from the mid-seventeenth century to the present day. This period saw major changes in gesture and bodily habitus which we could characterise in three ways. First, there is the decline of uniformity, that is, the gradual abandonment of attempts to enforce bodily uniformity as a means of social discipline, whether in religious worship or in other forms of collective social activity. Secondly, there is the process that sociologists have labelled the decline of deference, whereby individuals in the modern West are, for the most part, no longer required to kneel or bow to social superiors, or to use gestures of reverence in sacred spaces. Lastly, there is the decline of formality, a growing discomfort with formal ritual which could also be described in terms of interiority or individualism, as a belief that the mind rather than the body is the true locus of selfhood. In all these respects it would be rather easy to see the world of early modern religion described in this book as a world we have lost. But I want to argue that this model is unsatisfactory, or at least incomplete.
Chapter 6 shows how female subordination was expressed and symbolised through head-covering, following St Paul’s injunction that ‘the woman ought to have power on her head because of the angels’ (1 Cor. 11: 10). While some theologians, including Calvin, sought to reinterpret the text figuratively rather than literally, the Reformation never completely lost sight of the idea of the church building as a sacred space hallowed by the presence of the angels. This idea was taken up in the early seventeenth century by Laudian divines who used it to promote the gesture of bowing to the altar. More surprisingly, it was also supported by a handful of non-Laudian divines, including Joseph Mede and Paul Micklethwaite. This complicates the standard picture of the early Stuart church as divided between Laudians and their opponents, and suggests that the Laudians were tapping into a more widespread concern about declining standards of reverence in public worship. It also challenges the view that the Reformation witnessed a desacralisation of sacred space, by showing how the belief in the sacredness of churches not only persisted long into the early modern period but rested specifically on the notion of supernatural presence.
Chapter 1 explores the use of gesture in preaching, with reference to the branch of rhetoric known as pronunciatio, which provided the theoretical basis for much of the discussion of gesture in the early modern period. The basic rules of pronunciatio were derived from classical sources, but were developed and adapted by sixteenth-century writers on sacred rhetoric. All these writers were united by a shared insistence on the need for decorum and moderation, but in the early seventeenth century a contrast began to emerge between the techniques favoured by Reformed theologians in the Ramist tradition, who stressed the importance of bodily restraint and self-control, and the more dramatic style of preaching pioneered by Jesuit rhetoricians in France. One of the unexpected findings of this chapter is that the Jesuit style was widely admired and copied by seventeenth-century English Protestant preachers as a way of giving their sermons more emotional impact. Against the common assumption of an anti-theatrical prejudice in early modern Protestantism, we should think of a dynamic relationship between the pulpit and the stage in which preachers and actors watched and learned from each other.