Chronic liver disease (CLD) is frequently diagnosed at a late stage when prognosis is poor. We aimed to determine the patient factors associated with a late CLD diagnosis and its subsequent impact on survival to support early diagnosis initiatives. We identified participants of UK biobank (UKB) study who developed first-time advanced CLD within 5 years. We identified the factors associated with late diagnosis via logistic regression and used survival analysis to measure the association between late CLD diagnosis and mortality risk. A total of 725 UKB participants developed first-time advanced CLD event within 5 years. In total, 83% of cases were diagnosed late. Late diagnosis was associated with aetiology; the odds of late diagnosis were 12 times higher for an individual with alcohol-related liver disease (ArLD) vs viral hepatitis (aOR12.01; P<0.001). Cumulative mortality 5 years after incident advanced CLD was 43.4% (95% CI39.6-47.0). Late diagnosis was associated with a higher risk of postadvanced CLD mortality for patients with non-alcoholic fatty liver disease (aHR2.18; 95% CI0.86-5.51; P=0.10), but not for other aetiologies. Late CLD diagnosis varies according to aetiology and is highest for patients with ArLD and non-alcoholic fatty liver disease. The association between late diagnosis and postadvanced CLD mortality may also vary by aetiology. Late CLD diagnosis varies according to aetiology and is highest for patients with ArLD and non-alcoholic fatty liver disease. The association between late diagnosis and postadvanced CLD mortality may also vary by aetiology.Protease expression is closely linked to various pathological phenomena, and their accurate quantification is essential to clinical diagnosis and cancer therapy. Herein, we demonstrate for the first time the construction of a sensitive protease sensor by integrating protease-sensitive cleavage with nicking enzyme-assisted signal amplification (NESA) for single-molecule detection of multiple matrix metalloproteinases (MMPs). This protease sensor involves two DNA-peptide conjugates which contain both specific protease cleavage sites and trigger DNAs and two report DNAs which are modified with a fluorophore (Cy3 or Cy5) and a quencher (BHQ2). In the presence of specific MMPs, MMPs-mediated cleavage reactions lead to the release of specific trigger DNAs from the corresponding DNA-peptide conjugates. After the magnetic separation, the resultant trigger DNAs may hybridize with the corresponding report DNAs to initiate the cyclic NESA reaction, releasing large amounts of Cy3/Cy5 fluorescent molecules which can be simply quantified by using total internal reflection fluorescence-based single-molecule detection. Taking advantage of the high specificity of proteolytic cleavage, the high amplification efficiency of cyclic NESA, and the high sensitivity of single-molecule detection, this protease sensor can simultaneously detect multiple MMPs with a detection limit of 3.33 pM for MMP-2 and 1.71 pM for MMP-7, superior to the target peptide-based methods. Moreover, this protease sensor can be applied for the measurement of MMP-2 and MMP-7 in cancer cells and the screening of protease inhibitors, holding great promise in clinic diagnosis and drug discovery.Food allergens cause worldwide chronic diseases with a great impact on public health. Immunoglobulins E (IgEs) trigger allergic reactions by specifically binding the allergens to which the allergic patients are sensitized. In this scientific work we report for the first time a new optical interferometric in vitro system for the detection of specific IgEs (sIgEs) to the principal peach allergen (Pru p 3) in real serum samples. Interferometric Optical Detection Method (IODM) was employed for reading out the signal of Fabry-Perot based interferometers acting as biotransducers. https://www.selleckchem.com/products/npd4928.html Pru p 3 was immobilized as bioreceptor onto the sensing surface for detecting the target biomolecules, sIgEs to Pru p 3. Moreover, the demanding low concentration of IgE, compared to other analytes in real serum samples, made it necessary to use nanoparticles (NPs) for two reasons to collect only the IgEs from the serum sample and to enhance the optical interferometric read-out signal. The methodology was validated in advance by scanning electron microscopy (SEM). Consequently, we report in this article a novel high-performance in vitro detection method to recognize sIgE to molecular allergens by means of silicon dioxide (SiO2) NPs. Finally, this scientific work provides the basis for the in vitro component resolved diagnosis (CRD) of sIgEs to molecular allergens. To compare the effectiveness of directed open-glottis and directed closed-glottis pushing. Pragmatic, randomised, controlled, non-blinded superiority study. Four French hospitals between July 2015 and June 2017 (2 academic hospitals and 2 general hospitals). 250 women in labour who had undergone standardised training in the two types of pushing with a singleton fetus in cephalic presentation at term (≥37 weeks) were included by midwives and randomised; 125 were allocated to each group. The exclusion criteria were previous caesarean birth or fetal heart rate anomaly. Participants were randomised during labour, after a cervical dilation ≥ 7 cm. In the intervention group, open-glottis pushing was defined as a prolonged exhalation contracting the abdominal muscles (pulling the stomach in) to help move the fetus down the birth canal. Closed-glottis pushing was defined as Valsalva pushing. The principal outcome was "effectiveness of pushing" defined as a spontaneous birth without any episiotomy, second-ffer between the open- and closed-glottis groups. If directed pushing is necessary, women should be able to choose the type of directed pushing they prefer to use during birth. Professionals must therefore be trained in both types so that they can adequately support women as they give birth. If directed pushing is necessary, women should be able to choose the type of directed pushing they prefer to use during birth. Professionals must therefore be trained in both types so that they can adequately support women as they give birth.