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Schizophrenia and mood disorders -including unipolar depression and bipolar disorder-, are severe mental diseases with a highly heterogeneous symptomatology, among which cognitive dysfunction has progressively emerged as a key cornerstone. Patients suffering from these illnesses show significant deficits in different neurocognitive and social cognition domains. These deficits are evident during acute episodes, and in a high percentage of patients persist in periods of recovery, playing a decisive role on functional and clinical outcome. Nowadays, different pharmacological therapies have been tested, obtaining non-conclusive results. In this context, non-pharmacological strategies, such as neurocognitive remediation, have emerged as promising therapeutic intervention. Neurocognitive remediation comprises a program to rehabilitate cognitively impaired subjects, aiming either to restore their cognitive functioning or to compensate them in specific cognitive domains. One evolving approach, beginning to receive attention for its initial promising results, is computerized cognitive training. This technique employs tasks or games that exercise a particular brain function which target specific neural networks in order to improve cognitive functioning through neuroplasticity in a given neural circuit. In this scenario, we report our recent results with neuropersonaltrainer®-MH; a module for neurocognitive remediation consisting in a computerized telerehabilitation platform that enables cognitive remediation programs to be carried out in an intensive and personalized manner. Our group has applied NPTMH® in a pilot study treating patients with early onset psychotic disorder with positive and promising results, involving an improvement in functionality, neurocognition, and social cognition performance. Furthermore, new trials in bipolar disorder and major depressive disorder have been recently started.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results: In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions: In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.
The effects of plerocercoids of the cestode Triaenophorus nodulosus infecting the livers of native Eurasian perch Perca fluviatilis and non-native pumpkinseed Lepomis gibbosus was investigated in 17 sites along the Moselle watershed. With a single exception, infected individuals were not observed in the main channel whether or not northern pike Esox lucius, a final host, was present. In ponds where the pike was present, the prevalence of T. nodulosus averaged 86% in Eurasian perch and 15% in pumpkinseed. The parasite was not present at all in ponds when pike were absent. Parasite load, hepatosomatic index (HSI), gonadosomatic index (GSI) and body condition index (CI) were compared between hosts in one site where parasite prevalence and fish abundance was highest. HSI in infected perch was significantly higher than in uninfected perch, whereas no differences in HSI were detected between infected and uninfected pumpkinseed. While perch were more frequently infected and had a greater average parasite load than pumpkinseed, there were no significant differences in either indicator between the two species. Furthermore, no significant differences in GSI or CI were observed between infected and uninfected fish in either species, by either gender or maturity stage. We hypothesize that pumpkinseed is more resistant to the parasite or less likely to feed upon infected copepods than perch.
Scholarly assessments of Chaucer's fabliaux seldom acknowledge that these tales are erotic as well as funny; even less frequently do such investigations delve into why fabliaux are a source of pleasure. As Tom Hanks and W. W. Allman note in their article ‘Rough Love: Notes toward an Erotics of The Canterbury Tales’, scholars seem ‘to have averted their gaze when Chaucer's characters leap into bed’. Allman and Hanks, as their title implies, study an erotics of violence, mostly of men doing violence to women, and they focus in particular on the Merchant's Tale and its ‘erotics of stabbing’. A more positive erotic reading of the Merchant's Tale appears in Andrew Taylor's 1996 essay ‘Reading the Dirty Bits’. Taylor notes the lingering gaze of another scholar, E. Talbot Donaldson, upon a description of young May's body:
Hir fresshe beautee and hir age tendre,
Hir myddel smal, hire armes longe and sklendre,
Hir wise governaunce, hir gentilesse,
Hir wommanly berynge, and hire sadnesse.
Donaldson writes, ‘the Spring of pretty young girls is a permanent thing, and that May in their personas will always warm the masculine heart’. Taylor suggests that pleasure taken in this description and in Donaldson's gloss of it is mimetic: ‘For the young college man to share Donaldson's and Chaucer's pleasure in May is to become, like them, a connoisseur of both good writing and pretty girls, a master of ironic detachment and well-modulated heterosexual desire’.
As Roger Ascham famously observed, Malory's Morte Darthur is primarily concerned with ‘open manslaughter, and bold bawdry’. I would not disagree; in fact, I would say that these themes are not only dominant but are inextricably interwoven. Male sexuality, in Malory, is consistently portrayed as potentially violent and disruptive, dangerous not only to individuals but to the whole structure of society, and therefore in need of controlling measures. The medieval world did not, of course, often portray any form of sexuality positively. Sexual desire leads both men and women to sin: both directly in committing fornication, incest and adultery, and indirectly in committing treason or disregarding their duties. It could easily be assumed that this is a divide between the clergy on the one side, themselves compelled to live in celibacy and thus suspicious of sexual desire, and the more relaxed nobility and commons on the other, cheerfully ignoring the rules when it suited them. However, this is too simple a dichotomy. Malory himself, despite the bold bawdry, shares in the suspicion of unregulated desire, in his nostalgia for a chaster time,
nowadayes men can nat love sevennyght but they muste have all their desyres … But the olde love was nat so. for men and women coulde love togydirs seven yerys, and no lycoures lustis was betwyxte them, and than was love trouthe and faythefulnes.
In her seminal 1980 essay Pouvoirs de l'horreur, Julia Kristeva identifies ‘the abject’ as the human reaction to a breakdown in meaning caused by the loss of distinction between the subject and the object, the interior and the exterior, or the self and the Other. Her classic example of a site of abjection is that of the human corpse, which although a continuation of the dead person's corporeal presence also becomes simultaneously a marker of his or her spiritual absence, and thus must be rejected or repressed, causing the subjective experience of ‘horror’. Kristeva argues that human rationality necessarily involves a series of such repressions, and that the association of the human with the unrepressed thus becomes a site of potential tension. ‘The abject confronts us’, she suggests, ‘with those fragile states where man strays on the territories of animal’. This borderland between the acceptable and the unacceptable thus becomes the site of the carnivalesque, the comedic and the socially transgressive, as attested by post-medieval writers from Rabelais to Bakhtin and beyond.
In the first decade of the sixteenth century, the abject was also a major concern for the poet William Dunbar, writing at the court of King James IV. Dunbar's poems are critically regarded as some of the most brilliant – and, frequently, the most offensive – writings produced in late medieval/ early modern Scotland. Many of his satirical pieces depict the court of James (who would later go on to lose his life at the disastrous Battle of Flodden) at play, simultaneously parodying and affirming the excesses of late medieval/Renaissance aristocratic culture.
George Ripley, in his apostrophic preface to God in the Compound of Alchemy, claims to have ‘renounced … fleshly lust’ and asks God to provide him (and, presumably, other worthy alchemists) with His ‘secret treasure’: ‘Shew us thy secrets and to us be bounteous’ (21.4). Throughout the Compound, Ripley guides readers away from worldly pleasures, urging them instead to focus their desires on God-granted alchemical secrets and ‘our stone of great delight’ (37.2). Likewise, Thomas Norton, in his prologue to the Ordinal of Alchemy, warns of avaricious would-be alchemists who ‘in fyre / Of brennyng couetise haue therto desire’ (27–8). Norton emphatically shuns ‘wordly werkis’ in favour of alchemical ‘connyng’, advising his reader to ‘sett fully his trust’ in God and ‘in connyng be fixid al his lust’ (509, 517, 535–6): ‘For above all erthlye thynge / I mooste desire & love connynge’ (2595–6). Desire or lust, in both the Compound and the Ordinal, is thus redirected from the physical body and material world toward the divinely inspired knowledge of the alchemical corpus. Moreover, as I will illustrate, Norton and Ripley both direct their reader to focus on the text's rhetorical structures in order to achieve desired alchemical objectives.
In her 2007 essay ‘“Wordy vnthur wede”: Clothing, Nakedness and the Erotic in some Romances of Medieval Britain’, Amanda Hopkins examines the interplay of clothing and nudity in creating erotic moments, noting the connection of eroticism with female aggression on the one hand, and the erotic link between female nudity and passivity on the other. Lancelot's encounter with Elaine at Corbyn in Malory's Morte Darthur is marked by erotic moments featuring female nudity that appear emblematic of the latter. The eroticism of the moment when Lancelot rescues the ‘dolerous lady’ (2.791) from the boiling water by taking her by the hand, ‘naked as a nedyll’ (2.792), depends both on her total nudity and her status as victim – that is to say that the moment is erotic not just because she is naked, but because that nudity is not of her own making. Later, when Elaine ‘skypped oute of her bedde all naked’ (2.795) and kneels at Lancelot's feet to beg for her life, both her nudity and her vulnerability work to produce an erotic effect. Certainly Lancelot quickly changes his mind and turns from threatening her to embracing her. Yet to view Elaine as completely passive is a mistake – at the least her passivity is manipulated and Lancelot's presence in her bed is the result of machinations in which Elaine plays a willing part.
Sir Thopas's resolution to forsake human women in order to seek out an elf-queen as his lover satirizes one of the most well-known romance motifs: the fairy mistress who offers herself to the human protagonist of the narrative. It is characteristic of this motif that, with relatively few exceptions, the fairy offers sexual intercourse to the hero without any demand for the commitment of marriage and without stipulating any directly connected negative consequences. The motif's origins are a good deal earlier than those of romance – it features in several early medieval Irish narratives – but it is with romance that the motif is most particularly associated. It is noticeable that this extramarital sex is generally not explicitly condemned in the romances. Of course, romance authors are not prone to sermonizing digressions, so this might be passed over as merely a reflex of the genre; however, condemnation need not be overtly stated to still be clear and, in this respect, romance differs markedly from fabliaux, the other genre which frequently portrays extra-marital sex.
In the late fifteenth-century Squire of Low Degree, the incompetent protagonist woos a Hungarian princess in a way that seems to subject the romance genre to derivative, almost parodic, excess. This excess, however, offers particular insight into the representation of wooing in Middle English romance more broadly. While many romance heroines assume their suitors will display knightly prowess to win their love, this princess seems so aware of the Squire's shortcomings that she explains to him precisely what he must do, focusing on the rather boy-scout-like logistics of riding ‘Over hylles and dales, and hye mountaines, / In wethers wete, both hayle and raynes’, and lodging ‘under a tre, / Among the beastes wyld and tame’. Reminiscent here of how a Sir Thopas might understand chivalry, the text continues its overzealous attempt to ape romance when the princess exhaustively details the accoutrements that she expects from a suitor (203–30), and it is equally unable to find the right register when she offers to bankroll his required adventures (251–5). The envious steward's attempts to ruin the Squire by exposing his amorous inclinations are predictable enough; the results, however, have been seen as uncharacteristic of romance, since the king does not object to the Squire courting his daughter, but rather instructs the steward:
It is often said that the past is a foreign country where they do things differently, and perhaps no type of "doing" is more fascinating than sexual desires and behaviours. Our modern view of medieval sexuality is characterised bya polarising dichotomy between the swooning love-struck knights and ladies of romance on one hand, and the darkly imagined and misogyny of an unenlightened "medieval" sexuality on the other. British medieval sexual culture also exhibits such dualities through the influential paradigms of sinner or saint, virgin or whore, and protector or defiler of women. However, such sexual identities are rarely coherent or stable, and it is in the grey areas, the interstices between normative modes of sexuality, that we find the most compelling instances of erotic frisson and sexual expression. This collection of essays brings together a wide-ranging discussion of the sexual possibilitiesand fantasies of medieval Britain as they manifest themselves in the literature of the period. Taking as their matter texts and authors as diverse as Chaucer, Gower, Dunbar, Malory, alchemical treatises, and romances, the contributions reveal a surprising variety of attitudes, strategies and sexual subject positions. Contributors: Aisling Byrne, Anna Caughey, Kristina Hildebrand, Amy S. Kaufman, Yvette Kisor, Megan G. Leitch, Cynthea Masson, Hannah Priest, Samantha J. Rayner, Robert Allen Rouse, Cory James Rushton, Amy N. Vines.
Sampling of the fish community was carried out for 20 years in the Mirgenbach reservoir, in North-Eastern France. The prevalence and the mean intensity of Ligula intestinalis (Cestoda) were analysed in roach (Rutilus rutilus) and silver bream (Blicca bjoerkna) populations, the main two infected species. The aim of this study was to investigate the host switch from roach to silver bream and the consequences of L. intestinalis infestation in silver bream, which is an unusual host for this parasite as Ligula parasitism in silver bream appears to be rare. We analysed in detail the relationships between parasitism index (PI), gonadosomatic index (GSI), perivisceral fat abundance (PFA) and condition index (CI) in the silver bream population. In 1998, prevalence of L. intestinalis highlighted a clear host switch from roach to silver bream. In the silver bream population, young fish were the most severely infected and the impact of plerocercoids appeared to be different depending on the host sex. In male silver bream, plerocercoids drew energy from fat reserves even if GSI was also slightly impacted. On the contrary, in females energy was diverted from gonad maturation rather than from perivisceral fat reserves. No significant difference was observed in terms of CI in either sex.