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The aim of this study is to assess the evolution of respiratory and feeding support in children with spinal muscular atrophy (SMA) type 1 after 24 months of nusinersen treatment.
Methods:
Data on SMA type 1 children treated with nusinersen between 2017 and 2023 from the Canadian Neuromuscular Disease Registry were extracted. The cohort was divided into two groups based on age at treatment initiation: ≤2 years and >2 years. The primary outcome was the (i) time to death or needing full-time (≥16 hours/day) ventilation and (ii) time to needing feeding tube support. The secondary outcomes were differences in respiratory and feeding support requirements between the two groups at 24-month follow-up.
Results:
Thirty-two children were included, and the median age (range) for treatment initiation was 3.2 months (0.8– 13.1) in children who initiated treatment at ≤2 years and 51.2 (28.7–183.8) in those who initiated at >2 years of age. The median age of death or full-time ventilation was 8.6 months (6–22.4) and 10.5 months (4–24) for the two groups, respectively. The median age for initiation of feeding support was 5.1 (1.7–26.4) and 14.5 months (3.9–130.6), respectively. At 24 months (n = 23), there were no significant differences between the need for respiratory or feeding tube support between the two treatment groups.
Conclusion:
Most children with SMA type 1 treated with nusinersen across Canada have continued need for respiratory and feeding support over time when initiated after symptom onset.
We present a fully-automated workflow to map sea ice types from Sentinel-1 data and transfer the results in near real-time to the research vessel Kronprins Haakon (KPH) in order to support tactical navigation and decision-making during a research cruise conducted towards Belgica Bank in April and May 2022. We used overlapping SAR and optical imagery to train a pixel-wise classifier for the required season and region, and implemented a processing chain with the Norwegian Ice Service at MET Norway that automatically classifies all Sentinel-1 images covering the area of interest. During the cruise, classification results were available on KPH within hours after image acquisition, which is significantly faster than manually produced ice charts. We evaluate the results both quantitatively, based on manually selected validation regions, and qualitatively in comparison to in-situ observations and photographs. Our findings show that open water, level ice, and deformed ice are classified with high accuracy, while young ice remains challenging due to its variable small-scale surface roughness. This work presents one of the first attempts to transfer automated ice type classification results into the field in near real-time and contributes to bridging the gap between research and operations in automated sea ice mapping.
A major consideration for maritime activity in the Southern Hemisphere is the northern limit of icebergs, or the Southern Ocean Limit Of Known Ice (SOLOKI). This analysis of historical reports of icebergs during Southern Hemisphere voyages from 1687 to 1933 provides a basis for examination of their geographical and chronological occurrence during ~250 years. The analyses use tabulated data from 742 voyages and other reports from many sources, some including first-person descriptions. While these data are dependent on icebergs being reported by mariners, as well as the variable frequency of voyages, they demonstrate distinct periods of exceptional frequency of icebergs occurring in certain localities, particularly the far South Atlantic. Based upon historical records the evidence suggests unprecedented numbers of icebergs were present in southern shipping channels in the 1890s. When these historical observations are combined with modern iceberg drift trajectories, their possible origin can be elucidated. Owing to the numbers of icebergs seen and their geographical spread, our results suggest that this was possibly the largest near-synchronous calvings in the last 300 years, and the northernmost extent of the SOLOKI.
The problem of generating generally capable agents is an important frontier in artificial intelligence (AI) research. Such agents may demonstrate open-ended, versatile, and diverse modes of expression, similar to humans. We interpret the work of Heintz & Scott-Phillips as a minimal sufficient set of socio-cognitive biases for the emergence of generally expressive AI, separate yet complementary to existing algorithms.
Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.
Methods
Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).
Results
We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.
Conclusions
Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
Methods:
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
Results:
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Conclusion:
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Introduction: Lewis–Sumner syndrome (LSS) is a demyelinating peripheral neuropathy described in 1982. Methods: We reviewed the charts of nine LSS patients in neurological care for their symptoms, response to different treatment regimens, and pattern of nerve involvement. Results: One patient had an Adie’s pupil. Every patient studied had median nerve involvement. Seven of nine patients required intravenous immunoglobulin (IVIg) therapy and all showed improvement with IVIg. Four of nine patients received oral steroid therapy and had some improvement. Two of nine patients received azathioprine to little effect. Two of nine patients experienced significant trauma while receiving neurological follow-up and their symptoms worsened to a clinically significant degree afterward. Discussion: We noticed a possible association between trauma and symptom severity in cases of LSS with preexisting neurological follow-up. We hypothesize that physical trauma exacerbates LSS. To our knowledge, this is an unreported phenomenon.
The practice of anchoritism - religious enclosure which was frequently solitary and voluntarily embraced, very often in a permanent capacity - was widespread in many areas of Europe throughout the middle ages. Originating in the desert withdrawal of the earliest Christians and prefiguring even the monastic life, anchoritism developed into an elite vocation which was popular amongst both men and women. Within this reclusive vocation, the anchorite would withdraw, either alone or with others like her or him, to a small cell or building, very frequently attached to a church or other religious institution, where she or he would - theoretically at least - remain locked up until death. In the later period it was a vocation which was particularly associated with pious laywomen who appear to haveopted for this extreme way of life in their thousands throughout western Europe, often as an alternative to marriage or remarriage, allowing them, instead, to undertake the role of 'living saint' within the community.
This volume brings together for the first time in English much of the most important European scholarship on the subject to date. Tracing the vocation's origins from the Egyptian deserts of early Christian activity through to its multiple expressions in western Europe, it also identifies some of those regions - Wales and Scotland, for example - where the phenomenon doesnot appear to have been as widespread. As such, the volume provides an invaluable resource for those interested in the theories and practices of medieval anchoritism in particular, and the developmentof medieval religiosity more widely.
Dr LIZ HERBERT MCAVOY is Senior Lecturer in Gender in English and Medieval Studies at Swansea University.
CONTRIBUTORS: Anneke B. Mulder-Bakker, Gabriela Signori, M. Sensi, G. Cavero Dominguez, P. L'Hermite-Leclercq, Mari Hughes-Edwards, Colman O Clabaigh, Anna McHugh, Liz Herbert McAvoy.
In Le Temps retrouvé, Proust's Narrator complains about politics invading the space of literature. Thus writers who put before the demands of literature the search for justice, as in the Dreyfus Affair, or the advocacy of national unity in the context of the First World War, are rebuked by the Narrator: ‘How many . . . turn aside from writing!’ (6: 233; iv, 458). While this could be read biographically as the view of an author long embarked on a career of literary production, the forthright defence of the claims of literature belies the fact that the younger Proust responded with some urgency to major political events of his day. Thus in a letter of December 1919, a quarter of century after Dreyfus's initial conviction, Proust could still boast of his early role as an active defender of Dreyfus, who had been found guilty of spying for Germany in December 1894: ‘My signature was on the very first of the pro-Dreyfus lists and I was an ardent Dreyfusard, sending a copy of my first book to Picquart in the Cherche-Midi prison’ (Corr, xviii, 545).
The representations of the Dreyfus Affair in Proust's work are to be found principally in Jean Santeuil and À la recherche du temps perdu and they demonstrate a significant evolution in response, from the campaigning eagerness of the early novel to the retrospective consideration in the Recherche of a crisis, the intensity of which had been substantially diminished by the time of composition of the novel. Proust was an early believer in the innocence of the Jewish captain from Alsace who was humiliatingly stripped of his military rank at a degradation parade in January 1895 and imprisoned on L'Île du Diable. He worked to secure the support of Anatole France for the Dreyfus cause and in a letter of January 1899 congratulated the high-profile novelist on his intervention (Corr, ii, 272).
Renaissance Papers collects the best scholarly essays submitted each year to the Southeastern Renaissance Conference. The 2012 volume opens with two essays on sexuality in Elizabethan narrative poetry: on homoeroticism in Spenser's Faerie Queene and on Shakespeare's "swerve" into Lucretian imagery in Venus and Adonis. The volume then turns to Renaissance drama and its links to the wider culture: the commodification of spirit in Marlowe's Doctor Faustus, Shakespeare's evocation of the Acts of the Apostles in The Comedy of Errors, "summoning" in Hamlet and King Lear, discourses of procreation and generation in Antony and Cleopatra/, trade and gender in John Webster's Devil's Law-Case, and an examination of street scenes in Romeo and Juliet in relation to Paul's Cross Churchyard, the hub of the London bookselling market in the early modern period. The volume closes with essays on seventeenth-century literature and literary culture: on the "puritan logic" of the elder Andrew Marvell in his famous son's poem "To His Coy Mistress," on the "sociable lexicography" of a Royalist polymath attempting to reconcile with the English Commonwealth, and on the underestimated roles of Urania in Milton's Paradise Lost. Contributors: David Ainsworth, Thomas W. Dabbs, Sonya Freeman Loftis, Russell Hugh McConnell, Robert L. Reid, Amrita Sen, Susan C. Staub, Emily Stockard, Nathan Stogdill, Christina A. Taormina, Emma Annette Wilson. Andrew Shifflett and Edward Gieskes are Associate Professors of English at the University of South Carolina, Columbia.
Proust's public involvement in political campaigning preceded the years he spent working on À la recherche. His eager defence of Dreyfus is conveyed in Jean Santeuil where he delivers a forthrightly moral condemnation of judicial and military power, which is depicted as acting squarely in defence of la raison d'État. The other major issue on which he campaigned was Church–State relations. As an outspoken critic of the Combes government's policy of laicity, he opposed the separation of Church and State which was brought about in 1905. His ‘La mort des cathédrales’ [‘Death of the Cathedrals’] (Le Figaro, 16 August 1904) provides a cultural defence of France's religious heritage, seen in his lofty yet implicitly political view as the legacy of a medieval, Christian faithful who form ‘a great silent democracy’ (CSB, 149). Writing to Georges de Lauris on 29 July 1903 (in a letter which Proust refers to as stupid and embarrassing, and one to be destroyed by its addressee), he provides a revealing snapshot of his political thinking at this time. Reflecting both on ‘the dangerous mindset that gave rise to the [Dreyfus] Affair etc’ prevalent in the late 1890s and on the growth in anticlericalism, Proust argues that in both cases, ‘on travaille à faire deux France’ (Corr, iii, 382) [‘the thrust of political life is to divide the country in two’]. Concerned by ‘the fermenting of hatred among the French’ (Corr, iii, 383), Proust notes how the press reinforces prejudice in the laicity debate and stifles independent thinking. He was to restate this view in Le Temps retrouvé where Charlus points to newspaper readers' deluded belief in their autonomous actions: ‘“ce public qui ne juge ainsi des hommes et des choses de la guerre que par les journaux est persuadé qu'il juge par lui-même”. En cela M. de Charlus avait raison’ (iv, 367) [‘“this public which judges the men and events of the war solely from the newspapers, is persuaded that it forms its own opinions”. In this M. de Charlus was right’ (6: 122)]. Suspicious of virulent forms of nationalism during the First World War, Proust shows press influence to be a key agent of ideological formation.
Edited by
Andrew Shifflett, Associate Professor of English at the University of South Carolina, Columbia,Edward Gieskes, Associate Professor of English at the University of South Carolina, Columbia
Edited by
Andrew Shifflett, Associate Professor of English at the University of South Carolina, Columbia,Edward Gieskes, Associate Professor of English at the University of South Carolina, Columbia
With the recent shift in literary studies towards what is often described as a “global Renaissance,” it is hardly surprising that figures of merchants and travelers both in early modern travelogues and plays have come under greater scrutiny as sites for understanding the formation of a fluid English identity, transnational commerce, emergent colonialism, and nation building. What still remains largely unexplored, however, particularly in the context of the East Indies trade, is the impact of this emergent globalization on the bodies of the European women who were closely related to the merchants or factors. While scholarship on plays such as Fletcher's The Island Princess or Dryden's Amboyna emphasizes the roles of both European men and their beloved native women, the white woman still remains a shadowy presence at the fringes of our current academic interest in the early modern spice trade.
This essay seeks to address this gap by turning to the public stage, particularly to a play that explores how the emergent trade with the East Indies appeared to affect the physical and moral complexion of one such European woman. In the trial scene of John Webster's play The Devil's Law-Case (1623), Jolenta, the sister of Romelio, an East Indies merchant enters with “her face colour'd like that of a Moore,” accompanied by two Surgeons, “one of them like a Jew.” Although the assembled people quickly recognize her they still comment on her changed complexion. Ariosto the advocate exclaims, “Shee’s a blacke one indeed” (5.5.40) while Ercole, one of her suitors, wails “to what purpose / Are you thus ecclipst?” (5.5.57–58). Of course, Jolenta’s transformation is temporary and apparently superficial; yet her blackening appears to gesture towards deeper concerns regarding the impact of the East Indies trade, particularly on a woman who has never left her home or sailed the high seas to profit from pepper, cinnamon, cardamom and mace.
Edited by
Andrew Shifflett, Associate Professor of English at the University of South Carolina, Columbia,Edward Gieskes, Associate Professor of English at the University of South Carolina, Columbia
Edited by
Andrew Shifflett, Associate Professor of English at the University of South Carolina, Columbia,Edward Gieskes, Associate Professor of English at the University of South Carolina, Columbia
Gods apprentice is a jorneyman: he must allwayes learne the mystery of his profession, & walking forward aime hard to the marke for the price of his high calling. as the teacher in Gods schoole must give Line upon Line, precept upon precept: so to the scholler likewise nulla dies sine linea, no day must pass without a new lesson, as Cato said, so Gods child must grow old every day learning many things. And so in practise also. he must adde to his faith vertue, | & to plowing, sowing. Like Charles the fifth, plus ultra must be his motto: he must go from strength to strength untill he appeare be=fore the Lord in Sion. And that because, he is leaving his abode in this world but an im=perfect pilgrime. he is not what, he is not where he should be … [There are those who] ‘looke behind them, that turne their face in the day of battell, & quite give over Gods husbandry’, [those] ‘that forget their first love who though they forsake not the plough yet are they idle companions that do the worke of the Lord negligently … [For them] it had beene better never to have knowne the way of righ=teousness then that they should bee like a dog to his vomit & a sow to wallowing in the mire.