Poder escrit i successió al comtat d'Urgell (1188-1210)

This article is devoted to a series of records concerning rights of succession to the county of Urgell during the years 1188 to 1210. On two occasions Count Ermengol VIII received the sworn professions of fidelity to Countess Elvira, in case of Ermengol's death without heirs, from the people of his major towns in Urgell. And in 1210 King Pere I, acting as lord-protector of Urgell, received oaths of fidelity from the inhabitants of at least two of the same towns. The documents, seven in all, original parchments and (in 1210) papers, apparently unpublished, bear the names of those professing fidelity for Agramunt and Ponts (26-27 January 1188), for Agramunt, Ponts and Linyola (17 August 1206), and for Agramunt and Linyola (1 and 4 March and after 18 April 1210). These records raise questions about procedure, lordship, and the writing of power, and these matters are examined in turn. It is clear that the Count of Urgell laid claim to a quasi-vassalic lordship of homage and fidelity by the end of the twelfth century

The Scripts of Robert of Torigni: Some Notes of Conjectural History

This article argues that, while in agreement with B. Pohl that certain annotations in manuscripts of mid s. xii can safely be attributed to the hand of Robert of Torigni (RT), other passages (chiefly in Avranches, Bibliothèque patrimoniale, ms 210, fol. 112v-115r, and in ms 211, fol. 76r) cannot safely be attributed to anyone other than RT, or to a scribe working under his close direction. Moreover, certain markings in rubrics and datings of Leiden ms BPL 20 may be in RT’s hand. In addition, I conjecture that the notations .N. and .a. in several manuscripts dating mostly before 1154 were written by RT.Cet article entend montrer que, bien que B. Pohl ait raison d’attribuer certaines annotations figurant dans des manuscrits normands du milieu du XIIe siècle à la main de Robert de Torigni (RT), il existe d’autres passages (surtout dans ceux qui sont conservés dans la Bibliothèque patrimoniale d’Avranches, MS 210, fol. 112v-115r, et MS 211, fol. 76r) qui doivent avoir été copiés par RT lui-même ou par la main d’un autre scribe travaillant sous son étroite direction. De plus, certaines annotations dans les rubriques et les dates du ms Leiden BPL 20 peuvent être attribuées à la main de RT. Et, je soutiens que les notations .N. et .a. qui se trouvent dans quelques manuscrits écrits au Bec, surtout avant 1154, sont de la main de RT.L’articolo sostiene che, mentre in accordo con B. Pohl che certe annotazioni nei manoscritti di metà s. XII secolo possono essere attribuite alla mano di Roberto di Torigni (= RT), altri passi (principalmente in Avranches, Bibliothèque patrimoniale, ms 210, fol. 112v-115r, e in ms 211, fol. 76r) non possono essere attribuiti a nessuno al di fuori di RT, o a uno scriba che lavorava sotto la sua diretta direzione. Inoltre, alcuni segni nelle rubriche e nelle date del manoscritto Leiden ms BPL 20 possono essere scritti dalla mano di RT. Si ipotizza inoltre che le annotazioni .N. e .a. in diversi manoscritti risalenti per lo più prima del 1154 sono state scritte da RT

Adult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases

BACKGROUND: The presentation and causes of adult meningitis in South Africa have changed substantially as a result of HIV. Knowledge of aetiology and laboratory findings in patients presenting with meningitis are important in guiding management. We performed a retrospective study to determine these findings in a setting of high HIV and TB prevalence in Cape Town. METHODS: Patients undergoing lumbar punctures between 1st January 2006 and 31st December 2008 at a public sector referral hospital were studied. Cases were classified by microbiological diagnosis, or in the absence of definitive microbiology as 1) normal CSF (neutrophils or =1.5 mmol/L), 2) minor abnormalities (neutrophils 2-5, lymphocytes 6-20, protein 0.51-1.0, glucose 1.0-1.49) or 3) markedly abnormal (neutrophils>5, lymphocytes>20, protein>1.0, glucose<1.0). RESULTS: 5578 LPs were performed on 4549 patients, representing 4961 clinical episodes. Of these, 2293 had normal CSF and 931 had minor abnormalities and no aetiology identified. Of the remaining 1737, microbiological diagnoses were obtained in 820 (47%). Cryptococcus accounted for 63% (514) of microbiological diagnoses, TB for 28% (227), bacterial meningitis for 8% (68). Of the remaining 917 who had marked abnormalities, the majority (59%) had a sterile lymphocytic CSF. Of note 16% (81) patients with confirmed Cryptococcus, 5% (12) with TB and 4% (3) with bacterial meningitis had normal CSF cell-counts and biochemistry. CONCLUSIONS: Cryptococcal and tuberculous meningitis are now the commonest causes of adult meningitis in this setting. TB meningitis is probably underdiagnosed by laboratory investigation, as evidence by the large numbers presenting with sterile lymphocytic markedly abnormal CSFs

An Ecological Approach to Prospective and Retrospective Timing of Long Durations: A Study Involving Gamers

To date, most studies comparing prospective and retrospective timing have failed to use long durations and tasks with a certain degree of ecological validity. The present study assessed the effect of the timing paradigm on playing video games in a “naturalistic environment” (gaming centers). In addition, as it involved gamers, it provided an opportunity to examine the effect of gaming profile on time estimation. A total of 116 participants were asked to estimate prospectively or retrospectively a video game session lasting 12, 35 or 58 minutes. The results indicate that time is perceived as longer in the prospective paradigm than in the retrospective one, although the variability of estimates is the same. Moreover, the 12-minute session was perceived as longer, proportionally, than the 35- and 58-minute sessions. The study also revealed that the number of hours participants spent playing video games per week was a significant predictor of time estimates. To account for the main findings, the differences between prospective and retrospective timing are discussed in quantitative terms using a proposed theoretical framework, which states that both paradigms use the same cognitive processes, but in different proportions. Finally, the hypothesis that gamers play more because they underestimate time is also discussed

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Pragmatic randomised controlled trial of guided self-help versus individual cognitive behavioural therapy with a trauma focus for post-traumatic stress disorder (RAPID)

This is the final version. Available on open access from the NIHR Journals Library via the DOI in this recordData availability: All available data can be obtained from the corresponding author.BACKGROUND: Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs. OBJECTIVE: To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event. DESIGN: Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance. SETTING: Primary and secondary mental health settings across the United Kingdom's National Health Service. PARTICIPANTS: One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation. INTERVENTIONS: Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60-90 minutes, or to guided self-help using Spring, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions. MAIN OUTCOME MEASURES: Primary outcome: the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment. RESULTS: Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [mean difference 1.01 (one-sided 95% CI -∞ to 3.90, non-inferiority p = 0.012)]. Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural therapy with a trauma focus at this timepoint [mean difference 3.20 (one-sided 95% confidence interval -∞ to 6.00, non-inferiority p = 0.15)]. Guided self-help using Spring was not shown to be more cost-effective than face-to-face cognitive-behavioural therapy with a trauma focus although there was no significant difference in accruing quality-adjusted life-years, incremental quality-adjusted life-years -0.04 (95% confidence interval -0.10 to 0.01) and guided self-help using Spring was significantly cheaper to deliver [£277 (95% confidence interval £253 to £301) vs. £729 (95% CI £671 to £788)]. Guided self-help using Spring appeared to be acceptable and well tolerated by participants. No important adverse events or side effects were identified. LIMITATIONS: The results are not generalisable to people with post-traumatic stress disorder to more than one traumatic event. CONCLUSIONS: Guided self-help using Spring for mild to moderate post-traumatic stress disorder to a single traumatic event appears to be non-inferior to individual face-to-face cognitive-behavioural therapy with a trauma focus and the results suggest it should be considered a first-line treatment for people with this condition. FUTURE WORK: Work is now needed to determine how best to effectively disseminate and implement guided self-help using Spring at scale. TRIAL REGISTRATION: This trial is registered as ISRCTN13697710. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information.National Institute for Health and Care Research (NIHR

Conditionally reprogrammed primary airway epithelial cells maintain morphology, lineage and disease specific functional characteristics

© 2017 The Author(s). Current limitations to primary cell expansion led us to test whether airway epithelial cells derived from healthy children and those with asthma and cystic fibrosis (CF), co-cultured with an irradiated fibroblast feeder cell in F-medium containing 10 µM ROCK inhibitor could maintain their lineage during expansion and whether this is influenced by underlying disease status. Here, we show that conditionally reprogrammed airway epithelial cells (CRAECs) can be established from both healthy and diseased phenotypes. CRAECs can be expanded, cryopreserved and maintain phenotypes over at least 5 passages. Population doublings of CRAEC cultures were significantly greater than standard cultures, but maintained their lineage characteristics. CRAECs from all phenotypes were also capable of fully differentiating at air-liquid interface (ALI) and maintained disease specific characteristics including; defective CFTR channel function cultures and the inability to repair wounds. Our findings indicate that CRAECs derived from children maintain lineage, phenotypic and importantly disease-specific functional characteristics over a specified passage range