178 research outputs found
The national housing political system.
Massachusetts Institute of Technology. Dept. of City and Regional Planning. Thesis. 1968. M.C.P.13 unnumbered leaves inserted.Bibliography: leaves [95]-[99].M.C.P
Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study
Background:
Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack.
Methods:
Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316.
Findings:
Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively).
Interpretation:
In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation.
Funding:
The Stroke Association and the British Heart Foundation
Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial
Background
Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.
Methods
In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.
Findings
Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group.
Interpretation
Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.
Funding
London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation
Critical review on proteotypic peptide marker tracing for six allergenic ingredients in incurred foods by mass spectrometry
Peptide marker identification is one of the most important steps in the development of a mass spectrometry (MS) based method for allergen detection, since the robustness and sensitivity of the overall analytical method will strictly depend on the reliability of the proteotypic peptides tracing for each allergen. The European legislation in place issues the mandatory labelling of fourteen allergenic ingredients whenever used in different food formulations. Among these, six allergenic ingredients, namely milk, egg, peanut, soybean, hazelnut and almond, can be prioritized in light of their higher occurrence in food recalls for undeclared presence with serious risk decision. In this work, we described the results of a comprehensive evaluation of the current literature on MS-based allergen detection aiming at collecting all available information about proteins and peptide markers validated in independent studies for the six allergenic ingredients of interest. The main features of the targeted proteins were commented reviewing all details available about known isoforms and sequence homology particularly in plant-derived allergens. Several critical aspects affecting peptide markers reliability were discussed and according to this evaluation a final short-list of candidate markers was compiled likely to be standardized and implemented in MS methods for allergen analysis
Concert recording 2018-11-13
[Track 1]. Douzes etudes pour Caisse Claire. No. 1 / Jacques Delecluse -- [Track 2]. Ghost garden / Adam Hopper -- [Track 3]. Rotation no. 4 / Eric Sammut -- [Track 4]. Nine French-American rudimental solos. No. 6 / Unknown -- [Track 5]. Advanced studies for snare drum. No. 3 / Mitchell Peters -- [Track 6]. Tempest / Todd Ukena -- [Track 7]. Excerpt from Northern lights / Eric Ewazen -- [Track 8]. Caleidoscópio / Gene Koschinksi -- [Track 9]. Advanced studies for snare drum. No. 1 / Peters -- [Track 10]. Sweet dreams from Album for the young / Tchaikovsky arranged by L.H. Stevens -- [Track 11]. Furioso and valse in D minor / Earl Hatch -- [Track 12]. Pratt\u27s taps / William Schinstine -- [Track 13]. Max / J.C. Combs -- [Track 14]. Raga no. 1 / William Cahn -- [Track 15]. Sechs Miniaturen. No. 3 / Matthias Schmitt -- [Track 16]. Eden / Adam Miller -- [Track 17]. Four pieces for timpani. Mvts. 3 & 4 / John Bergamo -- [Track 18]. Swerve / Gene Kaschinski -- [Track 19]. White knuckle stroll / Casey Cangelosi -- [Track 20]. Evergreen / Benjamin Finley -- [Track 21]. Time remembered / Branden Steinmetz
Concert recording 2019-04-16
[Track 1]. Rotation #2 / Eric Sammut -- [Track 2]. Pines of Rome mvt 1 / Ottorino Respighi -- [Track 3]. Chart #2 / Fernando Valencia -- [Track 4]. Chopstakovich / Jesse Sieff -- [Track 5]. Drei Skizzen mvt. III / Matthias Schmitt -- [Track 6]. Sonata no. 1 for G in violoncello. Prelude [Track 7]. Sarabande [Track 8]. Courante / J.S. Bach -- [Track 9]. #1 from Douze Etudes / Jacques Delecluse -- [Track 10]. The offering / Michael Burritt -- [Track 11]. Prelude and blues / Ney Rosauro -- [Track 12]. Danny boy / traditional arranged by Brian Mueller -- [Track 13]. Ransom / Mark Ford -- [Track 14]. Sonata for timpani mvt III / John Beck -- [Track 15]. Dr. Gradus ad Parnassum / Claude Debussy arranged by Paul Bissell -- [Track 16]. Etude #1 / Vic Firth -- [Track 17]. Highlights from Northern lights / Eric Ewazen -- [Track 18]. Jesus loves me / Chad Floyd -- [Track 19]. Faded lines / Andrea Venet - [Track 20]. Triplets / George Hamilton Green arranged by Bob Becker -- [Track 21]. Girlfriends medley / Bob Becker -- [Track 22]. Selections from Oru Secu. Guaguancó [Track 23]. Guarapachangueo / Traditional trans. Valencia
Protein-protein interaction inhibition (2P2I)-oriented chemical library accelerates hit discovery
Protein-protein interactions (PPIs) represent an enormous source of opportunity for therapeutic intervention. We and others have recently pinpointed key rules that will help in identifying the next generation of innovative drugs to tackle this challenging class of targets within the next decade. We used these rules to design an oriented chemical library corresponding to a set of diverse 'PPI-like' modulators with cores identified as privileged structures in therapeutics. In this work, we purchased the resulting 1664 structurally diverse compounds and evaluated them on a series of representative protein-protein interfaces with distinct "druggability" potential using Homogeneous Time-Resolved Fluorescence (HTRF®) technology. For certain PPI classes, analysis of the hit rates revealed up to 100 enrichment factors compared with non-oriented chemical libraries. This observation correlates with the predicted "druggability" of the targets. A specific focus on selectivity profiles, the three-dimensional (3D) molecular modes of action resolved by X-ray crystallography, and the biological activities of identified hits targeting the well-defined "druggable" bromodomains of the bromo and extraterminal (BET) family are presented as a proof-of-concept. Overall, our present study illustrates the potency of machine learning-based oriented chemical libraries to accelerate the identification of hits targeting PPIs. A generalization of this method to a larger set of compounds will accelerate the discovery of original and potent probes for this challenging class of targets
Acute Severe Pain Is a Common Consequence of Sexual Assault
Sexual assault (SA) is common, but the epidemiology of acute pain after SA has not previously been reported. We evaluated the severity and distribution of pain symptoms in the early aftermath of SA among women receiving sexual assault nurse examiner (SANE) care, and the treatment of pain by SANE nurses. Severe pain (≥7 on a 0–10 numeric rating scale) was reported by 53/83 women sexual assault survivors (64% [95% CI, 53%–74%]) at the time of SANE evaluation and 43/83 women (52% [95% CI, 41%–63%]) one week later. Pain in four or more body regions was reported by 44/83 women (53% [95% CI, 42%–64%]) at the time of initial evaluation and 49/83 women (59% [95% CI, 48%–70%]) at one week follow-up. Among survivors with severe pain at the time of initial post-assault evaluation, only 7/53 (13% [95% CI, 6%–26%]) received any pain medication at the time of initial SANE treatment. These findings suggest that pain is common in SA survivors in the early post-assault period, but rarely treated
Professional training in organic food production: a cross-country experience
Purpose: The aim of this work was to characterize the agricultural activities and past experience in professional training in the context of mobile learning in different countries (Portugal, Spain, Slovakia, Hungary, United Kingdom, Italy and Turkey).
Design: For the survey, a questionnaire was prepared in English and Portuguese and then translated into the languages of the participating countries. It was delivered electronically for answering on-line by adults only. The participation was voluntary and in the end 133 consented valid questionnaires were obtained. For the treatment of the data was used SPSS and basic descriptive statistics tools were applied, together with tests, namely crosstabs and chi square tests, considering a level of significance of 5%.
Findings: The results showed that the majority of the participants presently have some agricultural activity and one third is thinking about starting one the future. Most of the participants want to produce food in organic mode, with significant differences among the countries at study. Most of the participants were enrolled in training activities in agriculture, especially those with higher education. This participation showed significant differences between countries and also according to the dimension of the farms owned by the participants. A significant association was found between being a teacher in forming activities related to agriculture and being a farmer. When compared to distance learning, the training activities in classroom were the most frequented, with significant differences among the countries.
Practical implications: This study allowed characterizing the learning activities in the field of organic agriculture and establish direction lines for planning of future training programs, in different countries, with maybe different social, educational and cultural realities
Originality/value: Because the study included the participation of people from several countries all around Europe, the results obtained enrich the scientific area of training in Organic Farming, in view of distance learning versus classroom learning on a more global basis.info:eu-repo/semantics/publishedVersio
Genetic Variation in the Familial Mediterranean Fever Gene (MEFV) and Risk for Crohn's Disease and Ulcerative Colitis
BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene. METHODOLOGY AND RESULTS: MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele. CONCLUSION: The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe
- …
