3,115 research outputs found

    Development and validation of a nomogram predicting recurrence risk in women with symptomatic urinary tract infection

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    Objectives: To develop and externally validate a novel nomogram predicting recurrence risk probability at 12 months in women after an episode of urinary tract infection. Methods: The study included 768women from Santa Maria Annunziata Hospital, Florence, Italy, affected by urinary tract infections from January 2005 to December 2009. Another 373 women with the same criteria enrolled at Santa Chiara Hospital, Trento, Italy, from January 2010 to June 2012 were used to externally validate and calibrate the nomogram. Univariate and multivariate Cox regression models tested the relationship between urinary tract infection recurrence risk, and patient clinical and laboratory characteristics. The nomogram was evaluated by calculating concordance probabilities, as well as testing calibration of predicted urinary tract infection recurrence with observed urinary tract infections. Nomogram variables included: number of partners, bowel function, type of pathogens isolated (Grampositive/ negative), hormonal status, number of previous urinary tract infection recurrences and previous treatment of asymptomatic bacteriuria. Results: Of the original development data, 261 out of 768 women presented at least one episode of recurrence of urinary tract infection (33.9%). The nomogram had a concordance index of 0.85. The nomogram predictions were well calibrated. This model showed high discrimination accuracy and favorable calibration characteristics. In the validation group (373 women), the overall c-index was 0.83 (P = 0.003, 95% confidence interval 0.51–0.99), whereas the area under the receiver operating characteristic curve was 0.85 (95% confidence interval 0.79–0.91). Conclusions: The present nomogram accurately predicts the recurrence risk of urinary tract infection at 12 months, and can assist in identifying women at high risk of symptomatic recurrence that can be suitable candidates for a prophylactic strategy

    Composite-pulse magnetometry with a solid-state quantum sensor

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    The sensitivity of quantum magnetometers is challenged by control errors and, especially in the solid-state, by their short coherence times. Refocusing techniques can overcome these limitations and improve the sensitivity to periodic fields, but they come at the cost of reduced bandwidth and cannot be applied to sense static (DC) or aperiodic fields. Here we experimentally demonstrate that continuous driving of the sensor spin by a composite pulse known as rotary-echo (RE) yields a flexible magnetometry scheme, mitigating both driving power imperfections and decoherence. A suitable choice of RE parameters compensates for different scenarios of noise strength and origin. The method can be applied to nanoscale sensing in variable environments or to realize noise spectroscopy. In a room-temperature implementation based on a single electronic spin in diamond, composite-pulse magnetometry provides a tunable trade-off between sensitivities in the microT/sqrt(Hz) range, comparable to those obtained with Ramsey spectroscopy, and coherence times approaching T1

    Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells

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    The members of MAGE gene family are highly expressed in human hepatocellular carcinoma (HCC). In the present study, we tested the tumour-specific MAGE-1 and MAGE-3 transcripts in the peripheral blood of HCC patients by nested RT–PCR to detect the circulating tumour cells and evaluate their potential clinical implication. Of 30 HCC patients, the positive rate of MAGE-1 and MAGE-3 transcripts was 43.3% (13 out of 30) and 33.3% (10 out of 30) in PBMC samples, whilst the positive rate was 70% (21 out of 30) and 53.3% (16 out of 30) in the resected HCC tissue samples, respectively. The positivity for at least one MAGE gene transcript was 63.3% (19 out of 30) in PBMC samples of HCC patients and 83.3% (25 out of 30) in the resected HCC tissue samples. MAGE-1 and/or MAGE-3 mRNA were not detected in the PBMC of those patients from whom the resected HCC tissues were MAGE-1 or MAGE-3 mRNA negative, nor in the 25 PBMC samples from healthy donors. The detection of MAGE transcripts in PBMC was correlated with the advanced stages and tumour size of the HCC, being 82.4% (14 out of 17) in tumour stages III and IVa, 56.6% (five out of nine) in stage II, and null (nought out of four) in stage I. The serum α-FP in 33.3% (10 out of 30) of HCC patients was normal or slightly elevated (<40 ng ml−1). However, six of these 10 patients (α-FP <40 ng ml−1) were MAGE-1 and /or MAGE-3 mRNA positive in their PBMC. The follow-up survey of MAGE mRNA in PBMC was performed in 12 patients. Seven patients with persistent MAGE-1 and/or MAGE-3 mRNA positive or from negative turned to positive died because of metastasis and/or recurrence. In striking contrast, all four patients with MAGE-1 and/or MAGE-3 mRNA from positive turned to negative and one patient with persistent MAGE-3 transcript negative are alive after last test. Collectively, detection of MAGE transcripts with follow-up survey in PBMC is a feasible and reliable assay for the early prediction of the relapse and prognosis of the HCC patients

    A random cell motility gradient downstream of FGF controls elongation of amniote embryos

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    Vertebrate embryos are characterized by an elongated antero-posterior (AP) body axis, which forms by progressive cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of cell motility and directionality in the PSM. We tracked the movement of the PSM extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells. After subtraction, cell motility remained graded but lacked directionality, indicating that the posterior cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of cell motion along the PSM parallels the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK) gradient1, which has been implicated in the control of cell motility in this tissue2. Both FGF signalling gain- and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with cell movement inhibitors (blebbistatin or RhoK inhibitor), but not cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements

    Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

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    Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ

    A novel class of microRNA-recognition elements that function only within open reading frames.

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    MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

    Beautiful Mirrors at the LHC

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    We explore the "Beautiful Mirrors" model, which aims to explain the measured value of AFBbA^b_{FB}, discrepant at the 2.9σ2.9\sigma level. This scenario introduces vector-like quarks which mix with the bottom, subtly affecting its coupling to the ZZ. The spectrum of the new particles consists of two bottom-like quarks and a charge -4/3 quark, all of which have electroweak interactions with the third generation. We explore the phenomenology and discovery reach for these new particles at the LHC, exploring single mirror quark production modes whose rates are proportional to the same mixing parameters which resolve the AFBbA_{FB}^b anomaly. We find that for mirror quark masses 500GeV,a14TeVLHCwith300fb1\lesssim 500 GeV, a 14 TeV LHC with 300 {\rm fb}^{-1} is required to reasonably establish the scenario and extract the relevant mixing parameters.Comment: version to be published in JHE

    Higgs boson production in photon-photon collision at ILC: a comparative study in different little Higgs models

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    We study the process \gamma\gamma->h->bb_bar at ILC as a probe of different little Higgs models, including the simplest little Higgs model (SLH), the littlest Higgs model (LH), and two types of littlest Higgs models with T-parity (LHT-I, LHT-II). Compared with the Standard Model (SM) prediction, the production rate is found to be sizably altered in these little Higgs models and, more interestingly, different models give different predictions. We find that the production rate can be possibly enhanced only in the LHT-II for some part of the parameter space, while in all other cases the rate is suppressed. The suppression can be 10% in the LH and as much as 60% in both the SLH and the LHT-I/LHT-II. The severe suppression in the SLH happens for a large \tan\beta and a small m_h, in which the new decay mode h->\eta\eta (\eta is a light pseudo-scalar) is dominant; while for the LHT-I/LHT-II the large suppression occurs when f and m_h are both small so that the new decay mode h->A_H A_H is dominant. Therefore, the precision measurement of such a production process at the ILC will allow for a test of these models and even distinguish between different scenarios.Comment: Version in JHEP (h-g-g & h-gamma-gamma expressions added
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