Atenolol versus losartan in children and young adults with Marfan's syndrome

BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period

A single fast radio burst localized to a massive galaxy at cosmological distance

Fast radio bursts (FRBs) are brief radio emissions from distant astronomical sources. Some are known to repeat, but most are single bursts. Nonrepeating FRB observations have had insufficient positional accuracy to localize them to an individual host galaxy. We report the interferometric localization of the single-pulse FRB 180924 to a position 4 kiloparsecs from the center of a luminous galaxy at redshift 0.3214. The burst has not been observed to repeat. The properties of the burst and its host are markedly different from those of the only other accurately localized FRB source. The integrated electron column density along the line of sight closely matches models of the intergalactic medium, indicating that some FRBs are clean probes of the baryonic component of the cosmic web

Macropodid herpesviruses 1 and 2 occupy unexpected molecular phylogenic positions within the Alphaherpesvirinae

The molecular phylogeny of macropodid herpesviruses 1 and 2 (MaHV-1 and -2) has been investigated by cloning and sequencing the genes encoding glycoprotein B from both viruses. Phylogenetic reconstructions based on the putative amino acid sequences of glycoprotein B indicate that MaHV-1 and -2 are most closely related to the subfamily Alphaherpesvirinae. Within the Alphaherpesvirinae, MaHV-1 and -2 are closely associated with those herpesviruses that infect primates. This phylogenetic relationship does not fit the constraints of the proposed co-evolution theory described for other members of the Alpherherpesvirinae which have mammalian hosts

Rapid and efficient construction of recombinant bovine herpesvirus 1 genomes

Bovine herpesvirus 1 (BoHV-1) is an important pathogen of cattle. Recombinant bovine herpesvirus 1 viruses (rBoHV) have been studied extensively as potential vaccines for BoHV-1 associated diseases. A method is described which advances protocols used currently for constructing rBoHV by producing recombinant viruses free of parent virus. The method, restriction endonuclease mediated recombination (REMR), utilises a unique NsiI site in the BoHV-1 genome. Following NsiI digestion the two genomic fragments are prevented from recombining by dephosphorylation. However, when the genomic fragments are co-transfected into a susceptible cell-line with a third DNA fragment (DNA bridge), which encodes DNA homologous to the digested viral termini, the three DNA molecules are able to undergo homologous recombination and produce infectious BoHV-1. During the recombination process foreign DNA within the DNA bridge is incorporated into the BoHV-1 genome, producing rBoHV. In the absence of the DNA bridge virus reconstitution does not occur thus eliminating contamination by the nonrecombinant parent virus. As REMR used an NsiI site occurring naturally in the BoHV-1 genome it can be used for the insertion of foreign DNA into the genome without any prior modifications. REMR could also be applied to any herpesvirus for which the genome sequence is known

The essential and non-essential genes of Bovine herpesvirus 1

Bovine herpesvirus 1 (BoHV-1) is an economically important pathogen of cattle associated with respiratory and reproductive disease. To further develop BoHV-1 as a vaccine vector, a study was conducted to identify the essential and non-essential genes required for in vitro viability. Randominsertion mutagenesis utilizing a Tn5 transposition system and targeted gene deletion were employed to construct gene disruption and gene deletion libraries, respectively, of an infectious clone of BoHV-1. Transposon insertion position and confirmation of gene deletion were determined by direct sequencing. The essential or non-essential requirement of either transposed or deleted open reading frames (ORFs) was assessed by transfection of respective BoHV-1 DNA into host cells. Of the 73 recognized ORFs encoded by the BoHV-1 genome, 33 were determined to be essential and 36 to be non-essential for virus viability in cell culture; determining the requirement of the two dual copy ORFs was inconclusive. The majority of ORFs were shown to conform to the in vitro requirements of BoHV-1 homologues encoded by human herpesvirus 1 (HHV-1). However, ORFs encoding glycoprotein K (UL53), regulatory, membrane, tegument and capsid proteins (UL54, UL49.5, UL49, UL35, UL20, UL16 and UL7) were shown to differ in requirement when compared to HHV-1-encoded homologues

Absolute quantitation of Marek's disease virus and Herpesvirus of turkeys in chicken lymphocyte, feather tip and dust samples using real-time PCR

The further development of Taqman quantitative real-time PCR (qPCR) assays for the absolute quantitation of Marek's disease virus serotype 1 (MDV1) and Herpesvirus of turkeys (HVT) viruses is described and the sensitivity and reproducibility of each assay reported. Using plasmid DNA copies, the lower limit of detection was determined to be 5 copies for the MDV1 assay and 75 copies for the HVT assay. Both assays were found to be highly reproducible for Ct values and calculated copy numbers with mean intra- and inter-assay coefficients of variation being less than 5% for Ct and 20% for calculated copy number. The genome copy number of MDV1 and HVT viruses was quantified in PBL and feather tips from experimentally infected chickens, and field poultry dust samples. Parallelism was demonstrated between the plasmid-based standard curves, and standard curves derived from infected spleen material containing both viral and host DNA, allowing the latter to be used for absolute quantification. These methods should prove useful for the reliable differentiation and absolute quantitation of MDV1 and HVT viruses in a wide range of samples

Aiding diagnosis and risk stratification for carotid atherosclerosis using mobility and strain patterns of the arterial wall

Σε αυτή την εργασία προσεγγίστηκε μια σπουδαία κλινική πρόκληση, η υποστήριξη της διάγνωσης της καρωτιδικής αθηρωμάτωσης, που ευθύνεται για την πλειονότητα των εγκεφαλικών επεισοδίων. Σε αυτή τη κατεύθυνση εξετάστηκε η δυνατότητα διάκρισης μεταξύ ασταθών και μη, αθηρωματικών πλακών στη καρωτίδα αρτηρία, μέσω της ανάλυσης ακολουθιών εικόνων υπερήχου. Έχοντας στη διάθεση μας έναν εκτιμητή κίνησης, που είχε ήδη υλοποιηθεί, βελτιστοποιηθεί και αξιολογηθεί για την εκτίμηση της κίνησης του αρτηριακού τοιχώματος, εφαρμόστηκε σε ακολουθίες εικόνων υπερήχου Β-σάρωσης για ένα σύνολο 96 ασθενών που πάσχουν από καρωτιδική αθηρωμάτωση. Τα αποτελέσματα από την εκτίμηση κίνησης για τον κάθε ασθενή χρησιμοποιήθηκαν για την παραγωγή 146 κατηγοριών κυματομορφών κίνησης, που αναπαριστούν μοτίβα κινήσεων και παραμορφώσεων σε σχέση με : (α) κινήσεις της αθηρωματικής πλάκας και των υγιών μερών του αρτηριακού τοιχώματος πλησίον της πλάκας, όπως και (β) τοπικές παραμορφώσεις και σχετικές κινήσεις του αρτηριακού τοιχώματος, αντίστοιχα. Αυτές οι κυματομορφές κίνησης τροφοδότησαν τα Κρυφά Μαρκοβιανά Μοντέλα (HMMs), που έχουν χρησιμοποιηθεί με μεγάλη επιτυχία στην αναγνώριση φωνής αλλά και σε πολλές άλλες εφαρμογές μηχανικής μάθησης. Στην περίπτωσή μας, τα HMMs χρησιμοποιήθηκαν για να αναγνωρίσουν περιπτώσεις κυματομορφών συμπτωματικών και ασυμπτωματικών ασθενών, με την αναλογία του ότι ο εκάστοτε ασθενής συνεισφέρει με τη δική του καρωτιδική αρτηριακή "προφορά" στο μοντέλο. Η απόδοση (ακρίβεια κατηγοριοποίησης) στα HMMs κυμάνθηκε μεταξύ 57.05% και 81.44% για τις 146 κατηγορίες κυματομορφών, με μέση απόδοση 69.95%. Τα αποτελέσματα αυτά επαληθεύτηκαν με την χρήση Μηχανών Διανυσμάτων Υποστήριξης (SVMs) στο ίδιο σύνολο δεδομένων, που κατηγοριοποιήθηκαν με μέση απόδοση 59%. Στην περίπτωση που επιλέχθηκαν, μονάχα, αυτές οι κατηγορίες κυματομορφών που παρουσίασαν τα υψηλότερα ποσοστά απόδοσης, τα HMMs μπόρεσαν να διακρίνουν ασυμπτωματικούς και συμπτωματικούς ασθενείς με απόδοση 75.81% και 73.91% αντίστοιχα, ενώ τα SVMs έφεραν αποτελέσματα 78.66% και 69.84% αντίστοιχα. Με δεδομένη την υπεροχή των SVMs, επιλέχθηκαν από αυτό το μοντέλο, οι συγκεκριμένες κατηγορίες κυματομορφών και δημιουργήθηκε ένα σύστημα πλειοψηφίας, για την υποστήριξη της διάγνωσης της ασθένειας. Η πλήρης δυναμική του συστήματος μένει να αποδειχθεί στο πλαίσιο μελλοντικών μελετών, σε μεγάλο πλήθος ασθενών με καρωτιδική αθηρωμάτωση οι οποίοι θα υποβληθούν σε συχνούς επανελέγχους, ενώ το σύστημα μπορεί να εμπλουτιστεί με πρόσθετα χαρακτηριστικά με χρονική εξέλιξη, όπως η αρτηριακή πίεση και ο καρδιακός ρυθμός.This thesis addressed a major clinical challenge, namely valid risk stratification for carotid atherosclerosis, which constitutes the most common cause of stroke. Toward this direction, we investigated the potential of spatiotemporal ultrasound image analysis in discriminating between stable and vulnerable atherosclerotic plaques of the carotid artery. To this end, a motion estimator, which has previously been designed, optimized and evaluated for arterial wall motion estimation, was applied to B-mode ultrasound image sequences of 96 patients with carotid atherosclerosis. The results of motion estimation for each patient were used to produce 146 types of motion waveforms, which represented mobility and strain patterns that express: (a) the movements of the atherosclerotic lesion (plaque) and the healthy parts of the arterial wall adjacent to the plaque, and (b) local deformations and relative movements in the arterial wall, respectively. These sets of motion waveforms were fed to Hidden Markov Models (HMMs), which have been successfully used in voice recognition and several other tasks of machine learning. In this case, HMMs were used to recognize motion waveforms of symptomatic and asymptomatic cases, intuitively considering that, for each patient, a motion waveform represents the "accent" of the carotid-artery wall. The performance (classification accuracy) of HMMs ranged between 57.05% and 81.44% for the 146 types of motion waveforms, while the average performance was 69.95%. These results were cross-validated using Support Vector Machines (SVMs) on the same dataset, which reached, an average of 59% classification accuracy. In the case that only the motion waveforms with the highest discrimination power were used, the HMMs could identify asymptomatic and symptomatic patients with 75.81% and 73.91% accuracy, respectively; the corresponding results for SVMs were 78.66% and 69.84%, respectively. Given the high performance in the latter case, those motion waveforms and their incorporation in SVMs were used to create a majority voting system for risk stratification for the disease. The full potential of the system will be revealed on future prospective studies with frequent patient follow-ups, while the system could be further enriched with other temporal features, such as the arterial pressure and heart rate.Μαρίνος Δ. Πρεβένιο

Nucleotide sequence of the histone gene cluster in the coral Acropora formosa (Cnidaria, Scleractinia): features of histone gene structure and organization are common to diploblastic and triploblastic metazoans

We report the nucleotide sequence of the core histone gene cluster from the Cnidarian Acropora formosa. This is the first histone gene cluster to be sequenced from a diploblastic organism and the predicted amino acid sequences most resemble those of sea urchin equivalents. Each of the Cnidarian histone genes has two conserved regions 3' of the coding sequences and these closely resemble those of the metazoan α-class histone genes. In A. formosa the core histone genes are arranged as opposed (H3/H4 and H2A/H2B) pairs, a pattern common to the nondeuterostome metazoa, and tandem repetition is the predominant pattern of organization in the Cnidarian. With the recent identification of several classes of homeobox genes in Cnidarians these features clearly align the Cnidaria with triploblastic metazoans, supporting a monophyletic origin of the metazoa

Associations between exposure to viruses and bovine respiratory disease in Australian feedlot cattle

Bovine respiratory disease (BRD) is the most important cause of clinical disease and death in feedlot cattle. Respiratory viral infections are key components in predisposing cattle to the development of this disease. To quantify the contribution of four viruses commonly associated with BRD, a case-control study was conducted nested within the National Bovine Respiratory Disease Initiative project population in Australian feedlot cattle. Effects of exposure to Bovine viral diarrhoea virus 1 (BVDV-1), Bovine herpesvirus 1 (BoHV-1), Bovine respiratory syncytial virus (BRSV) and Bovine parainfluenza virus 3 (BPIV-3), and to combinations of these viruses, were investigated. Based on weighted seroprevalences at induction (when animals were enrolled and initial samples collected), the percentages of the project population estimated to be seropositive were 24% for BoHV-1, 69% for BVDV-1, 89% for BRSV and 91% for BPIV-3. For each of the four viruses, seropositivity at induction was associated with reduced risk of BRD (OR: 0.6–0.9), and seroincrease from induction to second blood sampling (35–60 days after induction) was associated with increased risk of BRD (OR: 1.3–1.5). Compared to animals that were seropositive for all four viruses at induction, animals were at progressively increased risk with increasing number of viruses for which they were seronegative; those seronegative for all four viruses were at greatest risk (OR: 2.4). Animals that seroincreased for one or more viruses from induction to second blood sampling were at increased risk (OR: 1.4–2.1) of BRD compared to animals that did not seroincrease for any viruses. Collectively these results confirm that prior exposure to these viruses is protective while exposure at or after feedlot entry increases the risk of development of BRD in feedlots. However, the modest increases in risk associated with seroincrease for each virus separately, and the progressive increases in risk with multiple viral exposures highlights the importance of concurrent infections in the aetiology of the BRD complex. These findings indicate that, while efficacious vaccines could aid in the control of BRD, vaccination against one of these viruses would not have large effects on population BRD incidence but vaccination against multiple viruses would be expected to result in greater reductions in incidence. The findings also confirm the multifactorial nature of BRD development, and indicate that multifaceted approaches in addition to efficacious vaccines against viruses will be required for substantial reductions in BRD incidence