35,848 research outputs found
Human natural killer cell committed thymocytes and their relation to the T cell lineage.
Recent studies have demonstrated that mature natural killer (NK) cells can be grown from human triple negative (TN; CD3-, CD4-, CD8-) thymocytes, suggesting that a common NK/T cell precursor exists within the thymus that can give rise to both NK cells and T cells under appropriate conditions. In the present study, we have investigated human fetal and postnatal thymus to determine whether NK cells and their precursors exist within this tissue and whether NK cells can be distinguished from T cell progenitors. Based on the surface expression of CD56 (an NK cell-associated antigen) and CD5 (a T cell-associated antigen), three phenotypically distinctive populations of TN thymocytes were identified. CD56+, CD5-; CD56-, CD5-, and CD56-, CD5+. The CD56+, CD5- population of TN thymocytes, although displaying a low cytolytic function against NK sensitive tumor cell targets, were similar in antigenic phenotype to fetal liver NK cells, gave rise to NK cell clones, and were unable to generate T cells in mouse fetal thymic organ cultures (mFTOC). This population of thymocytes represents a relatively mature population of lineage-committed NK cells. The CD56-, CD5- population of TN thymocytes were similar to thymic NK cells in antigenic phenotype and NK cell clonogenic potential. Clones derived from this population of TN thymocytes acquired CD56 surface expression and NK cell cytolytic function. CD56-, CD5- TN thymocytes thus contain a novel population of NK cell-committed precursors. The CD56-, CD5- population of TN thymocytes also contains a small percentage of CD34+ cells, which demonstrate no in vitro clonogenic potential, but possess T cell reconstituting capabilities in mFTOC. The majority of TN thymocytes do not express CD56, but coexpress CD34 and CD5. These CD56-, CD5+, CD34+ cells demonstrate no NK or T cell clonogenic potential, but are extremely efficient in repopulating mFTOC and differentiating into CD3+, CD4+, CD8+ T cells. The results of this investigation have identified NK cells and NK cell precursors in the human thymus and have shown that these cell types are unable to differentiate along the T cell lineage pathway. Thus, while a common NK/T cell progenitor likely exists, once committed to the NK cell lineage these cells no longer have the capacity to develop along the T cell developmental pathway
Enhancing the top signal at Tevatron using Neural Nets
We show that Neural Nets can be useful for top analysis at Tevatron. The main
features of and background events on a mixed sample are projected in
a single output, which controls the efficiency and purity of the
signal.Comment: 11 pages, 6 figures (not included and available from the authors),
Latex, UB-ECM-PF 94/1
Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis
Background
Non-absorbable disaccharides (lactulose and lactitol) are recommended as first-line treatment for hepatic encephalopathy. The previous (second) version of this review included 10 randomised clinical trials (RCTs) evaluating non-absorbable disaccharides versus placebo/no intervention and eight RCTs evaluating lactulose versus lactitol for people with cirrhosis and hepatic encephalopathy. The review found no evidence to either support or refute the use of the non-absorbable disaccharides and no differences between lactulose versus lactitol.
Objectives
To assess the beneficial and harmful effects of i) non-absorbable disaccharides versus placebo/no intervention and ii) lactulose versus lactitol in people with cirrhosis and hepatic encephalopathy.
Search methods
We carried out electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 10), MEDLINE, EMBASE, and Science Citation Index Expanded to 19 October 2015; manual searches of meetings and conference proceedings; checks of bibliographies; and correspondence with investigators and pharmaceutical companies.
Selection criteria
We included RCTs, irrespective of publication status, language, or blinding.
Data collection and analysis
Two review authors, working independently, retrieved data from published reports and correspondence with investigators. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We presented the results of meta-analyses as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed the quality of the evidence using 'Grading of Recommendations Assessment Development and Evaluation' (GRADE) and bias control using the Cochrane Hepato-Biliary Group domains. Our analyses included regression analyses of publication bias and other small study effects, Trial Sequential Analyses to detect type 1 and type 2 errors, and subgroup and sensitivity analyses.
Main results
We included 38 RCTs with a total of 1828 participants. Eight RCTs had a low risk of bias in the assessment of mortality. All trials had a high risk of bias in the assessment of the remaining outcomes. Random-effects meta-analysis showed a beneficial effect of non-absorbable disaccharides versus placebo/no intervention on mortality when including all RCTs with extractable data (RR 0.59, 95% CI 0.40 to 0.87; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence) and in the eight RCTs with a low risk of bias (RR 0.63, 95% CI 0.41 to 0.97; 705 participants). The Trial Sequential Analysis with the relative risk reduction (RRR) reduced to 30% confirmed the findings when including all RCTs, but not when including only RCTs with a low risk of bias or when we reduced the RRR to 22%. Compared with placebo/no intervention, the non-absorbable disaccharides were associated with beneficial effects on hepatic encephalopathy (RR 0.58, 95% CI 0.50 to 0.69; 1415 participants; 22 RCTs; I2 = 32%; moderate quality evidence). Additional analyses showed that non-absorbable disaccharides can help to reduce serious adverse events associated with the underlying liver disease including liver failure, hepatorenal syndrome, and variceal bleeding (RR 0.47, 95% CI 0.36 to 0.60; 1487 participants; 24 RCTs; I2 = 0%; moderate quality evidence). We confirmed the results in Trial Sequential Analysis. Tests for subgroup differences showed no statistical differences between RCTs evaluating prevention, overt, or minimal hepatic encephalopathy. The evaluation of secondary outcomes showed a potential beneficial effect of the non-absorbable disaccharides on quality of life, but we were not able to include the data in an overall meta-analysis (very low quality evidence). Non-absorbable disaccharides were associated with non-serious (mainly gastrointestinal) adverse events (very low quality evidence). None of the RCTs comparing lactulose versus lactitol evaluated quality of life. The review found no differences between lactulose and lactitol for the remaining outcomes (very low quality evidence).
Authors' conclusions
This review includes a large number of RCTs evaluating the prevention or treatment of hepatic encephalopathy. The analyses found evidence that non-absorbable disaccharides may be associated with a beneficial effect on clinically relevant outcomes compared with placebo/no intervention.
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Plain language summary
Are non-absorbable disaccharides associated with beneficial or harmful effects in people with cirrhosis and hepatic encephalopathy?
Background
Cirrhosis is a chronic disorder of the liver. People with cirrhosis may develop hepatic encephalopathy, a condition that results in poor brain functioning. Hepatic encephalopathy may be clinically obvious (overt) with changes including poor concentration, tremor, and alterations in consciousness. Others have no obvious clinical changes (minimal) but, when tested, some aspects of brain function such as attention and the ability to perform complex tasks are impaired.
The reason why people develop hepatic encephalopathy is complex. The accumulation of ammonia plays a key role. The non-absorbable disaccharides, lactulose and lactitol, are indigestible sugars that reduce the levels of ammonia in the blood.
Review question
We investigated the use of non-absorbable disaccharides for the prevention and treatment of hepatic encephalopathy in people with cirrhosis by reviewing randomised clinical trials (RCTs).
Search date
The search date was October 2015.
Study funding sources
Seven RCTs received financial support and 11 RCTs received lactitol or inactive placebo free of charge from a pharmaceutical company.
Study characteristics
We included 29 RCTs comparing non-absorbable disaccharides with inactive placebo or no intervention and nine RCTs comparing lactulose with lactitol. Seven of the included RCTs evaluated the prevention of hepatic encephalopathy and 31 evaluated the treatment of hepatic encephalopathy. Sixteen of the treatment RCTs included people with overt hepatic encephalopathy while 15 included people with minimal hepatic encephalopathy. The duration of treatment varied depending on the type of hepatic encephalopathy from five days to one year.
Key results
People who received non-absorbable disaccharides were less likely to die than people given a placebo or no treatment. They were also less likely to develop serious complications of their liver disease such as liver failure, bleeding, and infections. The non-absorbable disaccharides were also effective in preventing the development of hepatic encephalopathy and increased the number of participants who recovered from hepatic encephalopathy. There was some evidence from a small number of trials that lactulose has a beneficial effect on the quality of life, but we were unable to include the data in an overall analysis. The non-absorbable disaccharides were associated with adverse events including diarrhoea, nausea, bloating, and flatulence. None of the RCTs comparing lactulose versus lactitol reported quality of life. The analyses showed no differences between the two interventions for the remaining outcomes.
Quality of the evidence
In the comparison of non-absorbable disaccharides versus placebo/no intervention, we found moderate quality evidence of benefit for the outcomes of death, hepatic encephalopathy, and serious complications. The evidence for the remaining outcomes was of very low quality
Secrecy content of two-qubit states
We analyze the set of two-qubit states from which a secret key can be
extracted by single-copy measurements plus classical processing of the
outcomes. We introduce a key distillation protocol and give the corresponding
necessary and sufficient condition for positive key extraction. Our results
imply that the critical error rate derived by Chau, Phys. Rev. A {\bf 66},
060302 (2002), for a secure key distribution using the six-state scheme is
tight. Remarkably, an optimal eavesdropping attack against this protocol does
not require any coherent quantum operation.Comment: 5 pages, RevTe
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