L'Ús d'escales clíniques en els ictus isquèmics secundaris a fibril·lació auricular

La FA és l'arítmia cardíaca més freqüent. És conegut el seu elevat potencial de produir esdeveniments tromboembòlics, com els ictus isquèmics. Aquests ictus cardioembòlics no solament són freqüents sinó també s'associen a una elevada morbi-mortalitat. És per aquest motiu que ens proposem estudiar-los en més profunditat. Així mateix, és conegut que no tots els pacients amb una FA tenen el mateix risc tromboembòlic. Diferents factors de risc cardiovasculars com l'edat avançada, la hipertensió arterial, la diabetis mellitus, entre d'altres, contribueixen a atorgar un risc anual de tromboembolisme. S'han creat múltiples escales per tal d'estratificar aquest risc. D'aquestes, la més emprada clàssicament ha estat la CHADS2 per la seva simplicitat. Però en el 2010 es publica l'escala CHA2DS2-VASc. El primer objectiu d'aquesta tesi és avaluar com classifica l'escala CHADS2 a una cohort de pacients en el moment previ al primer ictus isquèmic i comparar-ho amb la classificació si l'escala CHA2DS2-VASc hagués estat utilitzada. Els resultats d'aquest estudi mostren que la nova escala reclassifica a una gran part dels pacients que posteriorment pateixen un ictus, fora de la categoria de risc baix o intermedi, a una categoria on se'ls hauria d'haver indicat un tractament anticoagulant. Arrel de treballs com el nostre han canviat les recomanacions, tant en les guies europees com en les americanes, envers a ĺús de l'escala CHA2DS2-VASc per l'estratificació de risc. El segon objectiu ha estat avaluar l'ús d'aquesta nova escala CHA2DS2-VASc no només per estratificar el risc d'ictus sinó també la seva utilitat com a eina pronòstica en pacients que han patit un ictus isquèmic. Demostrem que per cada increment d'un punt en l'escala, s'incrementa un 36% la possibilitat de tenir un mal pronòstic als 3 mesos de l'ictus. En ambdues investigacions, trobem una baixa indicació de tractament anticoagulant en prevenció primària, en pacients d'alt risc, tot i l'efecte conegut clarament protector dels anticoagulants sobre la severitat de l'ictus, que es replica en el nostre estudi. La nostra línia d́investigació (amb el tercer treball) també s'ha orientat envers a la detecció d'un debut de fibril·lació auricular paroxística (FAp) un cop s'ha produït l'ictus, sobretot per la gran importància d'una correcta prevenció secundària, donat que la no detecció d'aquesta arítmia relega als pacients a un tractament clarament ineficient amb antiagregants plaquetaris. En la nostra cohort d'ictus isquèmics no seleccionats, que ingressen a la unitat d'ictus, diagnostiquem un 11.2% de FAp. Analitzem quins són els factors clínics que s'associen a aquest debut en un anàlisis bivariant i posteriorment multivariant (que són l'edat avançada, el sexe femení, la severitat inicial de l'ictus i la història prèvia d'insuficiència cardíaca congestiva). D'aquest anàlisis obtenim uns riscos de debut de FAp segons cada perfil clínic, que hem representat en unes taules de risc per a la seva fàcil i immediata interpretació a l'arribada del pacientAF is the most common cardiac arrhythmia in clinical practice, and is a well-known risk factor for cardiogenic embolism. These cardioembolic strokes are frequent and associated with a substantial increased risk of morbidity and mortality. However the risk of stroke and thromboembolism in AF patients is not homogeneous. Different risk factors such as advancing age, hypertension and diabetes mellitus, among others, contribute to the annual thromboembolic risk. Various stroke risk-stratification schemes have been developed for people with AF. The CHADS2 was probably the most often used because of its simplicity. But in 2010 a new scale was published: CHA2DS2-VASc. The first purpose of this thesis was to evaluate how CHADS2 classifies a cohort of patients previous to its first ischemic stroke and compare this risk stratification if the CHA2DS2-VASc scale would have been used. The results of this study showed that this new scale reclassifies a lot of patients out of the category of low-intermediate risk, into a category in which anticoagulation would have been indicated. Studies like ours changed recommendations of both European and U.S guidelines towards the use of the CHA2DS2-VASc score as the main scheme to assess patientís stroke risk. The second objective of our thesis was to evaluate the use of this new scale, not only for risk stratification, but also as prognosis tool in patients who suffered a stroke. We found that each point increase in the scale is associated with a 36% increase in the risk for poor 90-day outcome, independently of stroke severity. In both works, we found a low use of anticoagulation in primary prevention for high risk patients, despite its well-established protective effect, that we were able to replicate. Our research is also orientated towards the detection of a new paroxysmal atrial fibrillation (pAF) in stroke patients, since undetected pAF would lead to a suboptimal secondary prevention with antiplatelet agents. Therefore in the third work, in our cohort with unselected patients, who were admitted in the stroke unit, we detected 11.2% of pAF until de three-month visit. We analyzed which are the clinical risk factors associated to this new diagnosis in a bivariate and afterwards a multivariate analysis (which were advancing age, female sex, initial stroke severity and previous history of congestive heart failure). From this analysis we obtained a risk for new pAF detection for each vascular risk profile, that we represented into two risk charts for easy and immediately interpretation at patientís arrival

Quantum critical states and phase transitions in the presence of non equilibrium noise

Quantum critical points are characterized by scale invariant correlations and correspondingly long ranged entanglement. As such, they present fascinating examples of quantum states of matter, the study of which has been an important theme in modern physics. Nevertheless very little is known about the fate of quantum criticality under non equilibrium conditions. In this paper we investigate the effect of external noise sources on quantum critical points. It is natural to expect that noise will have a similar effect to finite temperature, destroying the subtle correlations underlying the quantum critical behavior. Surprisingly we find that in many interesting situations the ubiquitous 1/f noise preserves the critical correlations. The emergent states show intriguing interplay of intrinsic quantum critical and external noise driven fluctuations. We demonstrate this general phenomenon with specific examples in solid state and ultracold atomic systems. Moreover our approach shows that genuine quantum phase transitions can exist even under non equilibrium conditions.Comment: 9 pages, 2 figure

Long-term Shedding of Influenza A Virus in Stool of Immunocompromised Child

In immunocompromised patients, influenza infection may progress to prolonged viral shedding from the respiratory tract despite antiviral therapy. We describe chronic influenza A virus infection in an immunocompromised child who had prolonged shedding of culturable influenza virus in stool

Risk and protective indicators of beekeeping management practices

Explaining the reasons for the high honey bee (Apis mellifera) colony loss rate in recent years has become a top global research priority in apicultural and agricultural sciences. Although there are indications of the role played by beekeeping management practices on honey bee health, very little information is currently available. Our study aimed to characterize the beekeeping management practices carried out in Belgium, and to determine the relationship between beekeeping management practices and colony losses. Variables obtained from face-to-face questioning of a representative randomized and stratified sample of Belgian beekeepers (n = 186) were integrated into a logistic regression model (univariate and multivariate) and correlated to the declared colony loss rates to identify risk and protective indicators. We used a classification tree analysis to validate the results. We present evidence of a relationship between poor beekeeping management practices and colony losses. The main factors protecting honey bee colonies are the aptitude of the beekeeper to change his management practices, the hive type, the equipment origin and hygiene, wintering in proper conditions (the use of divider boards, i.e. board blocks or space fillers off part of the hive body), the colony strength estimation before wintering, winter monitoring, and last but not least, appropriate integrated pest management. Proper estimation of the Varroa infestation level should be performed prior to treatment. The consequences of poor beekeeping practices on honey bee health can be addressed by proper training of beekeepers. An online tool was developed and published for beekeepers allowing them to evaluate the effect of their management practices on colony health. (c) 2021 Elsevier B.V. All rights reserved

One-way trip: Influenza virus' adaptation to gallinaceous poultry may limit its pandemic potential

We hypothesise that some influenza virus adaptations to poultry may explain why the barrier for human-to-human transmission is not easily overcome once the virus has crossed from wild birds to chickens. Since the cluster of human infections with H5N1 influenza in Hong Kong in 1997, chickens have been recognized as the major source of avian influenza virus infection in humans. Although often severe, these infections have been limited in their subsequent human-to-human transmission, and the feared H5N1 pandemic has not yet occurred. Here we examine virus adaptations selected for during replication in chickens and other gallinaceous poultry. These include altered receptor binding and increased pH of fusion of the haemagglutinin as well as stalk deletions of the neuraminidase protein. This knowledge could aid the delivery of vaccines and increase our ability to prioritize research efforts on those viruses from the diverse array of avian influenza viruses that have greatest human pandemic potential

A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

© 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

Novel avian-origin influenza A (H7N9) virus attaches to epithelium in both upper and lower respiratory tract of humans

Influenza A viruses from animal reservoirs have the capacity to adapt to humans and cause influenza pandemics. The occurrence of an influenza pandemic requires efficient virus transmission among humans, which is associated with virus attachment to the upper respiratory tract. Pandemic severity depends on virus ability to cause pneumonia, which is associated with virus attachment to the lower respiratory tract. Recently, a novel avian-origin H7N9 influenza A virus with unknown pandemic potential emerged in humans. We determined the pattern of attachment of two genetically engineered viruses containing the hemagglutinin of either influenza virus A/Shanghai/1/13 or A/Anhui/1/13 to formalin-fixed human respiratory tract tissues using histochemical analysis. Our results show that the emerging H7N9 virus attached moderately or abundantly to both upper and lower respiratory tract, a pattern not seen before for avian influenza A viruses. With the caveat that virus attachment is only the first step in the virus replication cycle, these results suggest that the emerging H7N9 virus has the potential both to transmit efficiently among humans and to cause severe pneumonia

Time scales of Li evolution: a homogeneous analysis of open clusters from ZAMS to late-MS

We have performed a new and homogeneous analysis of all the Li data available in the literature for main sequence stars (spectral-types from late F to K) in open clusters. In the present paper we focus on a detailed investigation of MS Li depletion and its time scales for stars in the 6350-5500 K effective temperature range. For the first time, we were able to constrain the age at which non-standard mixing processes, driving MS Li depletion, appear. We have also shown that MS Li depletion is not a continuous process and cannot be simply described by a t^(-alpha) law. We confirm that depletion becomes ineffective beyond an age of 1-2 Gyr for the majority of the stars, leading to a Li plateau at old ages. We compared the empirical scenario of Li as a function of age with the predictions of three non-standard models. We found that models including only gravity waves as main mixing process are not able to fit the Li vs. age pattern and thus this kind of mixing can be excluded as the predominant mechanism responsible for Li depletion. On the other hand, models including slow mixing induced by rotation and angular momentum loss, and in particular those including also diffusive processes not related to rotation, can explain to some extent the empirical evidence. However, none of the currently proposed models can fit the plateau at old ages.Comment: 20 pages, 10 figures A&A accepte