127 research outputs found
Application of prognostic scores in the STOPAH trial: discriminant function is no longer the optimal scoring system in alcoholic hepatitis
No full textBACKGROUND & AIMS: 'Static' prognostic models in alcoholic hepatitis, using data from a single time point, include the discriminant function (DF), Glasgow alcoholic hepatitis score (GAHS), the age, serum bilirubin, international normalized ratio and serum creatinine (ABIC) score and the model of end-stage liver disease (MELD). 'Dynamic' scores, incorporating evolution of bilirubin at seven days, include the Lille score. The aim of this study was to assess these scores' performance in patients from the STOPAH trial.METHODS: Predictive performance of scores was assessed by area under the receiver operating curve (AUC). The effect of different therapeutic strategies upon survival was assessed by Kaplan-Meier analysis and tested using the log-rank test.RESULTS: A total of 1,068 patients were studied. The AUCs for the DF were significantly lower than for MELD, ABIC and GAHS for both 28- and 90-day outcomes: 90-day values were 0.670, 0.704, 0.726 and 0.713, respectively. 'Dynamic' scores and change in 'static' scores by Day 7 had similar AUCs. Patients with consistently low 'static' scores had low 28-day mortalities that were not improved with prednisolone (MELD <25: 8.6%; ABIC <6.71: 6.6%; GAHS <9: 5.9%). In patients with high 'static' scores without gastrointestinal bleeding or sepsis, prednisolone reduced 28-day mortality (MELD: 22.2% vs. 28.9%, p = 0.13; ABIC 14.6% vs. 21%, p = 0.02; GAHS 21% vs. 29.3%, p = 0.04). Overall mortality from treating all patients with a DF ≥32 and Lille assessment (90-day mortality 26.8%) was greater than combining newer 'static' and 'dynamic' scores (90-day mortality: MELD/Lille 21.8%; ABIC/Lille 23.7%; GAHS/Lille 20.6%).CONCLUSION: MELD, ABIC and GAHS are superior to the DF in alcoholic hepatitis. Consistently low scores have a favourable outcome not improved with prednisolone. Combined baseline 'static' and Day 7 scores reduce the number of patients exposed to corticosteroids and improve 90-day outcome.LAY SUMMARY: Alcoholic hepatitis is a life-threatening condition. Several scores exist to determine the outcome of these patients as well as to identify those who may benefit from treatment. This study looked at the performance of existing scores in patients who had been recruited to the largest alcoholic hepatitis clinical trial: STOPAH. 'Static' scores are calculable at the start of assessment. The three newer static scores (ABIC, GAHS and MELD) were shown to be superior to the oldest score (DF). ABIC and GAHS could also identify patients who had a survival benefit 28 days after starting prednisolone treatment. 'Dynamic' scores relate to the change in disease over the first week of treatment. Combination of the 'static' scores 'with the 'dynamic' scores or change in 'static' scores allowed identification of patients who could benefit from prednisolone up to 90 days.</p
Disfluency in dialogue:an intentional signal from the speaker?
No full textDisfluency is a characteristic feature of spontaneous human speech, commonly seen as a consequence of problems with production. However, the question remains open as to why speakers are disfluent: Is it a mechanical by-product of planning difficulty, or do speakers use disfluency in dialogue to manage listeners' expectations? To address this question, we present two experiments investigating the production of disfluency in monologue and dialogue situations. Dialogue affected the linguistic choices made by participants, who aligned on referring expressions by choosing less frequent names for ambiguous images where those names had previously been mentioned. However, participants were no more disfluent in dialogue than in monologue situations, and the distribution of types of disfluency used remained constant. Our evidence rules out at least a straightforward interpretation of the view that disfluencies are an intentional signal in dialogue
Sparrows can't sing : East End kith and kinship in the 1960s
No full textSparrows Can’t Sing (1963) was the only feature film directed by
the late and much lamented Joan Littlewood. Set and filmed in
the East End, where she worked for many years, the film deserves
more attention than it has hitherto received. Littlewood’s career
spanned documentary (radio recordings made with Ewan MacColl
in the North of England in the 1930s) to directing for the stage
and the running of the Theatre Royal in London’s Stratford East,
often selecting material which aroused memories in local audiences
(Leach 2006: 142). Many of the actors trained in her Theatre
Workshop subsequently became better known for their appearances
on film and television. Littlewood herself directed hardly any material
for the screen: Sparrows Can’t Sing and a 1964 series of television
commercials for the British Egg Marketing Board, starring Theatre
Workshop’s Avis Bunnage, were rare excursions into an area of practice
which she found constraining and unamenable (Gable 1980: 32).
The hybridity and singularity of Littlewood’s feature may answer,
in some degree, for its subsequent neglect. However, Sparrows Can’t
Sing makes a significant contribution to a group of films made in
Britain in the 1960s which comment generally on changes in the
urban and social fabric. It is especially worthy of consideration,
I shall argue, for the use which Littlewood made of a particular
community’s attitudes – sentimental and critical – to such changes and
for its amalgamation of an attachment to documentary techniques
(recording an aural landscape on location) with a preference for nonnaturalistic
delivery in performance
Identification of autophosphorylation sites in eukaryotic elongation factor-2 kinase
No full texteEF2K [eEF2 (eukaryotic elongation factor 2) kinase] phosphorylates and inactivates the translation elongation factor eEF2. eEF2K is not a member of the main eukaryotic protein kinase superfamily, but instead belongs to a small group of so-called ?-kinases. The activity of eEF2K is normally dependent upon Ca2+ and calmodulin. eEF2K has previously been shown to undergo autophosphorylation, the stoichiometry of which suggested the existence of multiple sites. In the present study we have identified several autophosphorylation sites, including Thr348, Thr353, Ser366 and Ser445, all of which are highly conserved among vertebrate eEF2Ks. We also identified a number of other sites, including Ser78, a known site of phosphorylation, and others, some of which are less well conserved. None of the sites lies in the catalytic domain, but three affect eEF2K activity. Mutation of Ser78, Thr348 and Ser366 to a non-phosphorylatable alanine residue decreased eEF2K activity. Phosphorylation of Thr348 was detected by immunoblotting after transfecting wild-type eEF2K into HEK (human embryonic kidney)-293 cells, but not after transfection with a kinase-inactive construct, confirming that this is indeed a site of autophosphorylation. Thr348 appears to be constitutively autophosphorylated in vitro. Interestingly, other recent data suggest that the corresponding residue in other ?-kinases is also autophosphorylated and contributes to the activation of these enzymes [Crawley, Gharaei, Ye, Yang, Raveh, London, Schueler-Furman, Jia and Cote (2011) J. Biol. Chem. 286, 2607-2616]. Ser366 phosphorylation was also detected in intact cells, but was still observed in the kinase-inactive construct, demonstrating that this site is phosphorylated not only autocatalytically but also in trans by other kinases
Changes in hospital discharges with alcohol-related liver disease in a gastroenterology and general medical unit following the introduction of minimum unit pricing of alcohol: the GRI Q4 study
No full textAims:
Minimum unit price (MUP) of 50 pence per unit of alcohol was introduced in Scotland on the 1 May 2018. We assessed alcohol-related liver disease (ArLD) discharges from Glasgow Royal Infirmary (GRI) before and after the introduction of MUP.
Methods:
Medical records of all patients discharged from Gastroenterology wards at GRI in the fourth quarter (Q4) of the years 2015–2019 were reviewed. All patients with ArLD were identified, and detailed hospitalization data were collected retrospectively. Active drinking, severity scores, presence of alcoholic hepatitis (AH) and 90-day mortality and readmission rates were assessed.
Results:
There were fewer ArLD discharges per quarter after MUP than before (mean 80.3 pre-MUP; mean 68 post-MUP), and the proportion of active drinkers was lower post-MUP (64.7 vs. 70.5%). There was a significant fall in the mean number of weekly discharges of individual patients who were actively drinking (4.0 ± 2.0 pre-MUP, 2.8 ± 1.5 post-MUP, P = 0.01). There were no differences in the proportion of patients presenting with ascites, encephalopathy or AH; however, there was a reduction in presentations with acute upper gastrointestinal bleeding from 15.8% pre-MUP to 7.4% post-MUP (P = 0.02; odds ratio 0.42). Severity of liver disease remained unchanged. The 90-day mortality and readmission rates were not significantly different.
Conclusion:
Since the introduction of MUP there has been a reduction in the absolute numbers of patients discharged with ArLD and the number of individual patients involved at GRI. The pattern of clinical presentation was largely unaffected with overall ArLD severity, readmission rates and 90-day mortality similar pre- and post-MUP
Acute haemodynamic changes after oral carvedilol, a vasolidating beta-blocker, in patients with cirrhosis
No full textINDIGENOUS LAND TENURE AND LAND USE IN ALASKA: COMMUNITY IMPACTS OF THE ALASKA NATIVE CLAIMS SETTLEMENT ACT
No full textThrough the utilization of qualitative methods such as archival analysis, semi-structured interviewing, comparative and extended case studies, and observation, this paper closely examines two related Alaska Native communities. Our purpose is to document the impact of the Alaska Native Claims Settlement Act of 1971 (ANCSA) on land tenure, land use, and community structure. In all, 41 interviews were conducted, focusing on the following issues: (1) the role of the tribal government in relation to the regional and village corporate structure; (2) the recent changes in traditional land uses; and (3) how group decisions are made regarding land management and distribution of resources. By locating ANCSA within a broader context of economic, political, and cultural globalization that seeks to substitute traditional collective rights in land with individual tenure in a "free market" economy, the findings of this research may carefully and cautiously be applied beyond North America to other indigenous-state struggles regarding control of land and resources.United States. -- [Alaska Native Claims Settlement Act], Indians of North America -- Legal status, laws, etc. -- Alaska, Land tenure -- Law and legislation -- Alaska, Indians of North America -- Alaska -- Claims, Indians of North America -- Land tenure -- Alaska, Indians of North America -- Alaska -- Government relations -- History, Land Economics/Use,
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