FibroTest, transient elastography method, and combined FibroTest and transient elastography method for diagnosis of severe hepatic fibrosis and cirrhosis in adults with chronic hepatitis C

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the diagnostic accuracy of FibroTest, transient elastography method, combined FibroTest and transient elastography method, no matter the sequence, using liver biopsy as reference standard, for assessment of severe hepatic fibrosis and cirrhosis in adults with chronic hepatitis C without any co-infections such as hepatitis B, HIV, and alcoholic liver disease. To compare the accuracy of FibroTest, transient elastography method, combined FibroTest and transient elastography method, for assessment of hepatic fibrosis in adults with chronic hepatitis C. To explore heterogeneity analysing the following study factors: different grade of inflammation according to the liver biopsy; different lengths of liver biopsy sample; different number of portal tracts included in a liver biopsy sample; different serum levels of ALT activity. different grade of inflammation according to the liver biopsy; different lengths of liver biopsy sample; different number of portal tracts included in a liver biopsy sample; different serum levels of ALT activity

Glucocorticosteroids for people with alcoholic hepatitis

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the benefits and harms of glucocorticosteroids in people with alcoholic hepatitis

Ultrasonography for diagnosis of alcoholic cirrhosis in people with alcoholic liver disease

BACKGROUND: Heavy alcohol consumption causes alcoholic liver disease and is a causal factor of many types of liver injuries and concomitant diseases. It is a true systemic disease that may damage the digestive tract, the nervous system, the heart and vascular system, the bone and skeletal muscle system, and the endocrine and immune system, and can lead to cancer. Liver damage in turn, can present as multiple alcoholic liver diseases, including fatty liver, steatohepatitis, fibrosis, alcoholic cirrhosis, and hepatocellular carcinoma, with presence or absence of hepatitis B or C virus infection. There are three scarring types (fibrosis) that are most commonly found in alcoholic liver disease: centrilobular scarring, pericellular fibrosis, and periportal fibrosis. When liver fibrosis progresses, alcoholic cirrhosis occurs. Hepatocellular carcinoma occurs in 5% to 15% of people with alcoholic cirrhosis, but people in whom hepatocellular carcinoma has developed are often co-infected with hepatitis B or C virus.Abstinence from alcohol may help people with alcoholic disease in improving their prognosis of survival at any stage of their disease; however, the more advanced the stage, the higher the risk of complications, co-morbidities, and mortality, and lesser the effect of abstinence. Being abstinent one month after diagnosis of early cirrhosis will improve the chance of a seven-year life expectancy by 1.6 times. Liver transplantation is the only radical method that may change the prognosis of a person with alcoholic liver disease; however, besides the difficulties of finding a suitable liver transplant organ, there are many other factors that may influence a person's survival.Ultrasound is an inexpensive method that has been used for years in clinical practice to diagnose alcoholic cirrhosis. Ultrasound parameters for assessing cirrhosis in people with alcoholic liver disease encompass among others liver size, bluntness of the liver edge, coarseness of the liver parenchyma, nodularity of the liver surface, size of the lymph nodes around the hepatic artery, irregularity and narrowness of the inferior vena cava, portal vein velocity, and spleen size.Diagnosis of cirrhosis by ultrasound, especially in people who are asymptomatic, may have its advantages for the prognosis, motivation, and treatment of these people to decrease their alcohol consumption or become abstinent.Timely diagnosis of alcoholic cirrhosis in people with alcoholic liver disease is the cornerstone for evaluation of prognosis or choosing treatment strategies. OBJECTIVES: To determine the diagnostic accuracy of ultrasonography for detecting the presence or absence of cirrhosis in people with alcoholic liver disease compared with liver biopsy as reference standard.To determine the diagnostic accuracy of any of the ultrasonography tests, B-mode or echo-colour Doppler ultrasonography, used singly or combined, or plus ultrasonography signs, or a combination of these, for detecting hepatic cirrhosis in people with alcoholic liver disease compared with liver biopsy as a reference standard, irrespective of sequence. SEARCH METHODS: We performed searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, The Cochrane Library (Wiley), MEDLINE (OvidSP), EMBASE (OvidSP), and the Science Citation Index Expanded to 8 January 2015. We applied no language limitations.We screened study references of the retrieved studies to identify other potentially relevant studies for inclusion in the review and read abstract and poster publications. SELECTION CRITERIA: Three review authors independently identified studies for possible inclusion in the review. We excluded references not fulfilling the inclusion criteria of the review protocol. We sent e-mails to study authors.The included studies had to evaluate ultrasound in the diagnosis of hepatic cirrhosis using only liver biopsy as the reference standard.The maximum time interval of investigation with liver biopsy and ultrasonography should not have exceeded six months. In addition, ultrasonography could have been performed before or after liver biopsy. DATA COLLECTION AND ANALYSIS: We followed the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. MAIN RESULTS: The review included two studies that provided numerical data regarding alcoholic cirrhosis in 205 men and women with alcoholic liver disease. Although there were no applicability concerns in terms of participant selection, index text, and reference standard, we judged the two studies at high risk of bias. Participants in both studies had undergone both liver biopsy and ultrasonography investigations. The studies shared only a few comparable clinical signs and symptoms (index tests).We decided to not perform a meta-analysis due to the high risk of bias and the high degree of heterogeneity of the included studies. AUTHORS' CONCLUSIONS: As the accuracy of ultrasonography in the two included studies was not informative enough, we could not recommend the use of ultrasonography as a diagnostic tool for liver cirrhosis in people with alcoholic liver disease. In order to be able to answer the review questions, we need diagnostic ultrasonography prospective studies of adequate sample size, enrolling only participants with alcoholic liver disease.The design and report of the studies should follow the Standards for Reporting of Diagnostic Accuracy. The sonographic features, with validated cut-offs, which may help identify clinical signs used for diagnosis of fibrosis in alcoholic liver disease, should be carefully selected to achieve maximum diagnostic accuracy on ultrasonography

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

Transient elastography with controlled attenuation parameter (CAP) for diagnosis of moderate or severe steatosis in people with suspected non-alcoholic fatty liver disease

Objectives: This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To determine the diagnostic accuracy of transient elastography with CAP for diagnosis of moderate and severe hepatic steatosis in people with suspected NAFLD when compared with liver biopsy as reference standard. To achieve this, we will compare none/mild hepatic steatosis (S0 to S1) versus moderate/severe hepatic steatosis (S2 to S3); and none/mild/moderate hepatic steatosis (S0 to S2) versus severe hepatic steatosis (S3). Secondary objectives: We aim to also identify the pooled sensitivity and specificity for the most common cut‐off values of CAP for diagnosis of none/mild hepatic steatosis (S0 to S1) and moderate/severe hepatic steatosis (S2 to S3); or none/mild/moderate hepatic steatosis (S0 to S2) and severe hepatic steatosis (S3) in people with suspected NAFLD, and to explore potential sources of heterogeneity influencing the diagnostic test accuracy of CAP (see: Investigations of heterogeneity)

Effect of venlafaxine on bone loss associated with ligature-induced periodontitis in Wistar rats

<p>Abstract</p> <p>Background</p> <p>The present study investigated the effects of venlafaxine, an antidepressant drug with immunoregulatory properties on the inflammatory response and bone loss associated with experimental periodontal disease (EPD).</p> <p>Materials and Methods</p> <p>Wistar rats were subjected to a ligature placement around the second upper left molar. The treated groups received orally venlafaxine (10 or 50 mg/kg) one hour before the experimental periodontal disease induction and daily for 10 days. Vehicle-treated experimental periodontal disease and a sham-operated (SO) controls were included. Bone loss was analyzed morphometrically and histopathological analysis was based on cell influx, alveolar bone, and cementum integrity. Lipid peroxidation quantification and immunohistochemistry to TNF-α and iNOS were performed.</p> <p>Results</p> <p>Experimental periodontal disease rats showed an intense bone loss compared to SO ones (SO = 1.61 ± 1.36; EPD = 4.47 ± 1.98 mm, p < 0.001) and evidenced increased cellular infiltration and immunoreactivity for TNF-α and iNOS. Venlafaxine treatment while at low dose (10 mg/kg) afforded no significant protection against bone loss (3.25 ± 1.26 mm), a high dose (50 mg/kg) caused significantly enhanced bone loss (6.81 ± 3.31 mm, p < 0.05). Venlafaxine effectively decreased the lipid peroxidation but showed no significant change in TNF-α or iNOS immunoreactivity.</p> <p>Conclusion</p> <p>The increased bone loss associated with high dose venlafaxine may possibly be a result of synaptic inhibition of serotonin uptake.</p

Glucocorticosteroids for people with alcoholic hepatitis

BACKGROUND: Alcoholic hepatitis is a form of alcoholic liver disease, characterised by steatosis, necroinflammation, fibrosis, and potential complications to the liver disease. Typically, alcoholic hepatitis presents in people between 40 and 50 years of age. Alcoholic hepatitis can be resolved if people abstain from drinking, but the risk of death will depend on the severity of the liver damage and abstinence from alcohol. Glucocorticosteroids are used as anti-inflammatory drugs for people with alcoholic hepatitis. Glucocorticosteroids have been studied extensively in randomised clinical trials in order to assess their benefits and harms. However, the results have been contradictory. OBJECTIVES: To assess the benefits and harms of glucocorticosteroids in people with alcoholic hepatitis. SEARCH METHODS: We identified trials through electronic searches in Cochrane Hepato-Biliary's (CHB) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, and Science Citation Index Expanded. We looked for ongoing or unpublished trials in clinical trials registers and pharmaceutical company sources. We also scanned reference lists of the studies retrieved. The last search was 20 October 2016. SELECTION CRITERIA: Randomised clinical trials assessing glucocorticosteroids versus placebo or no intervention in people with alcoholic hepatitis, irrespective of year, language of publication, or format. We considered trials with adult participants diagnosed with alcoholic hepatitis, which could have been established through clinical or biochemical diagnostic criteria or both. We defined alcoholic hepatitis as mild (Maddrey's score less than 32) and severe (Maddrey's score 32 or more). We allowed co-interventions in the trial groups, provided they were similar. DATA COLLECTION AND ANALYSIS: We followed Cochrane and CHB methodology, performing the meta-analyses using Review Manager 5 and Trial Sequential Analysis. We presented the results of dichotomous outcomes as risk ratios (RR) and those of the continuous outcomes as mean difference (MD). We applied both the fixed-effect model and the random-effects model meta-analyses. Whenever there were significant discrepancies in the results, we reported the more conservative point estimate of the two. We considered a P value of 0.01 or less, two-tailed, as statistically significant if the required information size was reached due to our three primary outcomes (all-cause mortality, health-related quality of life, and serious adverse events during treatment) and our post hoc decision to include analyses of mortality at more time points. We presented heterogeneity using the I² statistic. If trialists used intention-to-treat analysis to deal with missing data, we used these data in our primary analysis; otherwise, we used the available data. We assessed the bias risk of the trials using bias risk domains and the quality of the evidence using GRADE. MAIN RESULTS: Sixteen trials fulfilled the inclusion criteria. All trials were at high risk of bias. Fifteen trials provided data for analysis (927 participants received glucocorticosteroids and 934 participants received placebo or no intervention). The glucocorticosteroids were administered orally or parenterally for a median of 28 days (range 3 days to 12 weeks). The participants were between 25 and 70 years old, had different stages of alcoholic liver disease, and 65% were men. The follow-up of trial participants, when it was reported, was up to the moment of discharge from the hospital, until they died (a median of 63 days), or for at least a year. There was no evidence of effect of glucocorticosteroids on all-cause mortality up to three months following randomisation neither with traditional meta-analysis (random-effects RR 0.90, 95% CI 0.70 to 1.15; participants = 1861; trials = 15; I² = 45% (moderate heterogeneity) nor with Trial Sequential Analysis. Meta-analysis showed no evidence of effect on health-related quality of life up to three months (MD -0.04 points; 95% CI -0.11 to 0.03; participants = 377; trial = 1; low-quality evidence), measured with the European Quality of Life - 5 Dimensions-3 Levels (EQ- 5D-3L) scale. There was no evidence of effect on the occurrence of serious adverse events during treatment, neither with traditional meta-analysis (random-effects RR 1.05, 95% CI 0.85 to 1.29; participants = 1861; trials = 15; I² = 36% (moderate heterogeneity), liver-related mortality up to three months following randomisation (random-effects RR 0.89, 95% CI 0.69 to 1.14; participants = 1861; trials = 15; I² = 46% (moderate heterogeneity), frequency of any complications up to three months following randomisation (random-effects RR 1.04, 95% CI 0.86 to 1.27; participants = 1861; I² = 42% (moderate heterogeneity), and frequency of non-serious adverse events up to three months' follow-up after end of treatment (random-effects RR 1.99, 95% CI 0.72 to 5.48; participants = 160; trials = 4; I² = 0% (no heterogeneity) nor with Trial Sequential Analysis. Nine of the trials were industry-funded. AUTHORS' CONCLUSIONS: We found no evidence of a difference between glucocorticosteroids and placebo or no intervention on all-cause mortality, health-related quality of life, and serious adverse events during treatment. The risk of bias was high and the quality of evidence was very low or low. Therefore, we are very uncertain about this effect estimate. Due to inadequate reporting, we cannot exclude increases in adverse events. As the confidence intervals were wide, we cannot rule out significant benefits and harms of glucocorticosteroids. Therefore, we need placebo-controlled, randomised clinical trials, designed according to the SPIRIT guidelines and reported according to the CONSORT guidelines. Future trials ought to report depersonalised individual participant data, so that proper individual participant data meta-analyses of the effects of glucocorticosteroids in subgroups can be conducted

Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

Peer reviewe

Measurement of Higgs boson production and properties in the WW decay channel with leptonic final states

Peer reviewe

Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

Peer reviewe