High-throughput sequencing of small RNA transcriptomes reveals critical biological features targeted by microRNAs in cell models used for squamous cell cancer research

Abstract Background The implication of post-transcriptional regulation by microRNAs in molecular mechanisms underlying cancer disease is well documented. However, their interference at the cellular level is not fully explored. Functional in vitro studies are fundamental for the comprehension of their role; nevertheless results are highly dependable on the adopted cellular model. Next generation small RNA transcriptomic sequencing data of a tumor cell line and keratinocytes derived from primary culture was generated in order to characterize the microRNA content of these systems, thus helping in their understanding. Both constitute cell models for functional studies of microRNAs in head and neck squamous cell carcinoma (HNSCC), a smoking-related cancer. Known microRNAs were quantified and analyzed in the context of gene regulation. New microRNAs were investigated using similarity and structural search, ab initio classification, and prediction of the location of mature microRNAs within would-be precursor sequences. Results were compared with small RNA transcriptomic sequences from HNSCC samples in order to access the applicability of these cell models for cancer phenotype comprehension and for novel molecule discovery. Results Ten miRNAs represented over 70% of the mature molecules present in each of the cell types. The most expressed molecules were miR-21, miR-24 and miR-205, Accordingly; miR-21 and miR-205 have been previously shown to play a role in epithelial cell biology. Although miR-21 has been implicated in cancer development, and evaluated as a biomarker in HNSCC progression, no significant expression differences were seen between cell types. We demonstrate that differentially expressed mature miRNAs target cell differentiation and apoptosis related biological processes, indicating that they might represent, with acceptable accuracy, the genetic context from which they derive. Most miRNAs identified in the cancer cell line and in keratinocytes were present in tumor samples and cancer-free samples, respectively, with miR-21, miR-24 and miR-205 still among the most prevalent molecules at all instances. Thirteen miRNA-like structures, containing reads identified by the deep sequencing, were predicted from putative miRNA precursor sequences. Strong evidences suggest that one of them could be a new miRNA. This molecule was mostly expressed in the tumor cell line and HNSCC samples indicating a possible biological function in cancer. Conclusions Critical biological features of cells must be fully understood before they can be chosen as models for functional studies. Expression levels of miRNAs relate to cell type and tissue context. This study provides insights on miRNA content of two cell models used for cancer research. Pathways commonly deregulated in HNSCC might be targeted by most expressed and also by differentially expressed miRNAs. Results indicate that the use of cell models for cancer research demands careful assessment of underlying molecular characteristics for proper data interpretation. Additionally, one new miRNA-like molecule with a potential role in cancer was identified in the cell lines and clinical samples.

Muscular and pulmonary O2 uptake kinetics during moderate- and high-intensity sub-maximal knee-extensor exercise in humans

[EN] The purpose of this investigation was to determine the contribution of muscle O(2) consumption (mVO2) to pulmonary O(2) uptake (pVO2) during both low-intensity (LI) and high-intensity (HI) knee-extension exercise, and during subsequent recovery, in humans. Seven healthy male subjects (age 20-25 years) completed a series of LI and HI square-wave exercise tests in which mVO2 (direct Fick technique) and pVO2 (indirect calorimetry) were measured simultaneously. The mean blood transit time from the muscle capillaries to the lung (MTTc-l) was also estimated (based on measured blood transit times from femoral artery to vein and vein to artery). The kinetics of mVO2 and pVO2 were modelled using non-linear regression. The time constant (tau) describing the phase II pVO2 kinetics following the onset of exercise was not significantly different from the mean response time (initial time delay + tau) for mVO2 kinetics for LI (30 +/- 3 vs 30 +/- 3 s) but was slightly higher (P < 0.05) for HI (32 +/- 3 vs 29 +/- 4 s); the responses were closely correlated (r = 0.95 and r = 0.95; P < 0.01) for both intensities. In recovery, agreement between the responses was more limited both for LI (36 +/- 4 vs 18 +/- 4 s, P < 0.05; r = -0.01) and HI (33 +/- 3 vs 27 +/- 3 s, P > 0.05; r = -0.40). MTTc-l was approximately 17 s just before exercise and decreased to 12 and 10 s after 5 s of exercise for LI and HI, respectively. These data indicate that the phase II pVO2 kinetics reflect mVO2 kinetics during exercise but not during recovery where caution in data interpretation is advised. Increased mVO2 probably makes a small contribution to during the first 15-20 s of exercise.

Applicability of Process Mining Techniques in Business Environments

This thesis analyses problems related to the applicability, in business environments, of Process Mining tools and techniques. The first contribution is a presentation of the state of the art of Process Mining and a characterization of companies, in terms of their "process awareness". The work continues identifying circumstance where problems can emerge: data preparation; actual mining; and results interpretation. Other problems are the configuration of parameters by not-expert users and computational complexity. We concentrate on two possible scenarios: "batch" and "on-line" Process Mining. Concerning the batch Process Mining, we first investigated the data preparation problem and we proposed a solution for the identification of the "case-ids" whenever this field is not explicitly indicated. After that, we concentrated on problems at mining time and we propose the generalization of a well-known control-flow discovery algorithm in order to exploit non instantaneous events. The usage of interval-based recording leads to an important improvement of performance. Later on, we report our work on the parameters configuration for not-expert users. We present two approaches to select the "best" parameters configuration: one is completely autonomous; the other requires human interaction to navigate a hierarchy of candidate models. Concerning the data interpretation and results evaluation, we propose two metrics: a model-to-model and a model-to-log. Finally, we present an automatic approach for the extension of a control-flow model with social information, in order to simplify the analysis of these perspectives. The second part of this thesis deals with control-flow discovery algorithms in on-line settings. We propose a formal definition of the problem, and two baseline approaches. The actual mining algorithms proposed are two: the first is the adaptation, to the control-flow discovery problem, of a frequency counting algorithm; the second constitutes a framework of models which can be used for different kinds of streams (stationary versus evolving).

Exploring the biofilm of Streptococcus agalactiae to identify virulence factors

Streptococcus agalactiae, also known as Group B Streptococcus (GBS) is the primary colonizer of the anogenital mucosa of up to 40% of healthy women and an important cause of invasive neonatal infections worldwide. Among the 10 known capsular serotypes, GBS type III accounts for 30-76% of the cases of neonatal meningitis. Biofilms are dense aggregates of surface-adherent microorganisms embedded in an exopolysaccharide matrix. Centers for Disease Control and Prevention estimate that 65% of human bacterial infections involve biofilms (Post et al., 2004). In recent years, the ability of GBS to form biofilm attracted attention for its possible role in fitness and/or virulence. Here, a new in vitro biofilm formation protocol was developed to guarantee more stringent conditions, to better discriminate between strong-, low- and non- biofilm forming strains and reduce ambiguous data interpretation. This protocol was applied to screen the in vitro biofilm formation ability of more than 350 GBS clinical isolates from pregnant women and neonatal infections belonging to different serotype, in relation to media composition and pH. The results showed the enhancement of GBS biofilm formation in acidic condition and identified a subset of isolates belonging to serotypes III and V that forms strong biofilms in these conditions. Interestingly, the best biofilm formers belonged to the serotype III hypervirulent clone ST-17.It was also found that pH 5.0 induces down-regulation of the capsule but that this reduction is not enough by itself to ensure biofilm formation. Moreover, the ability of proteinase K to strongly inhibit biofilm formation and to disaggregate mature biofilms suggested that proteins play an essential role in promoting GBS biofilm formation and contribute to the biofilm structural stability. Finally, a set of proteins potentially expressed during the GBS in vitro biofilm formation were identified by mass spectrometry.

Untersuchungen zur autoimmunen Genese der thrombotisch thrombozytopenischen Purpura

Untersuchungen zur autoimmunen Genese der thrombotisch thrombozytopenischen Purpura. rnEinführung: Die idiopathische thrombotisch thrombozytopenische Purpura (TTP) ist eine lebensbedrohliche Mikroangiopathie und wird durch ein Autoantikörper-induziertes Defizit der ADAMTS13-Protease ausgelöst. Eine Assoziation zwischen Krankheitsprädisposition und Vorliegen bestimmter humaner Leukozytenantigene (HLA) wird vermutet. Untersuchungen zu diesem Zusammenhang stellen einen Teil dieser Arbeit dar. rnAutoimmunkrankheiten tendieren zum gemeinsamen Auftreten innerhalb eines Individuums. Im zweiten Teil dieser Arbeit wird untersucht, ob eine solche Kookkurrenz verschiedener Autoimmunkrankheiten auch bei Patienten mit idiopathischer TTP beobachtet werden kann.rnMethodik: Zur Untersuchung der ersten Fragestellung werden die HLA-Klasse I und II-Merkmale von 54 deutschen TTP-Patienten bestimmt. Alle Patienten weisen Autoantikörper gegen ADAMTS13 und eine Protease-Aktivität <5% vor. Die Blutproben werden mittels Sequence Specific Primer-Polymerase Chain Reaction (PCR) und Sequence Specific Oligonucleotid-PCR auf HLA-DRB1, -DRB3-5 und –DQB1 untersucht. Als Referenz dienen die Werte deutscher Knochenmark- und Blutspender, erhalten über www.allelefrequencies.net. Die statistische Auswertung erfolgt mittels zweiseitigem Binomialtest und die resultierenden p-Werte werden nach Benjamini-Hochberg korrigiert.rnZur Beantwortung der zweiten Fragestellung werden 76 deutsche TTP-Patienten anhand eines standardisierten Fragebogens nach Begleiterkrankungen befragt. Als Vergleichswerte dient die Prävalenz der jeweiligen Erkrankung in der Allgemeinbevölkerung. Die statistische Auswertung erfolgt mittels zweiseitigem Binomialtest. Da die p-Werte nicht korrigiert werden, sind die Ergebnisse nur deskriptiv zu verstehen.rnErgebnis: Der Vergleich der HLA-Frequenzen ergibt ein signifikant gehäuftes Vorkommen von HLA-DQB1*02:02 (p<0,001) und -DRB1*11 (p=0,003) innerhalb des Patientenkollektivs. 20% (DQB1*02:02) bzw. 48,1% (DRB1*11) der TTP-Patienten sind im Gegensatz zu nur 1,2% (DQB1*02:02) bzw. 23,5% (DRB1*11) innerhalb der Vergleichsgruppe für das jeweilige HLA-Merkmal positiv.rnDie Befragung der TTP-Patienten bezüglich weiterer Erkrankungen ergab im Vergleich mit der Allgemeinbevölkerung fünf auffällig häufig im Patientenkollektiv vorkommende Autoimmunkrankheiten: Hashimoto Thyreoiditis (23,5% in der Patientengruppe zu 0,7% in der Allgemeinbevölkerung; p<0,001), systemischer Lupus erythematodes (6,5% der Patienten im Gegensatz zu 0,025% in der Allgemeinbevölkerung, p<0,001), Immunthrombozytopenie (6,3% der Patienten zu 0,02% in der Allgemeinbevölkerung; p<0,001), Psoriasis (9,4% der Patienten zu 2,5% in der Allgemeinbevölkerung; p=0,005) und glutensensitive Enteropathie (3,1% der Patienten zu 0,2% in der Allgemeinbevölkerung; p=0,007). rnSchlussfolgerung: Das vermehrte Vorkommen bestimmter HLA-Merkmale im Patientenkollektiv spricht für eine prädisponierende Wirkung dieser Antigene im Krankheitsgeschehen. Eine mögliche HLA-vermittelte Assoziation zwischen TTP und den genannten Autoimmunkrankheiten wird vermutet, kann jedoch nicht in allen Fällen die beobachtete Kookkurrenz ausreichend erklären. Insgesamt bestätigt die vorliegende Arbeit die Assoziation verschiedener Autoimmunkrankheiten untereinander und spricht für eine genetische Prädisposition zur Ausbildung autoimmuner Störungen. rn

Etablierung eines high content imaging-basierten in vitro Testsystems zur Evaluierung genotoxischer Substanzen

Zur Registrierung von Pharmazeutika ist eine umfassende Analyse ihres genotoxischen Potentials von Nöten. Aufgrund der Vielzahl genotoxischer Mechanismen und deren resultierenden Schäden wird ein gestaffeltes Testdesign durch die ICH-Richtlinie S2(R1) „Guidance on genotoxicity testing and data interpretation for pharmaceuticals intended for human use S2(R1)“ definiert, um alle genotoxischen Substanzen zu identifizieren. Die Standardtestbatterie ist in der frühen Phase der Arzneimittelentwicklung aufgrund des geringen Durchsatzes und des Mangels an verfügbarer Substanzmenge vermindert anwendbar. Darüber hinaus verfügen in vitro Genotoxizitätstests in Säugerzellen über eine relativ geringe Spezifität. Für eine vollständige Sicherheitsbeurteilung wird eine in vivo Testung auf Kanzerogenität benötigt. Allerdings sind diese Testsysteme kosten- und zeitintensiv. Aufgrund dessen zielen neue Forschungsansätze auf die Verbesserung der Prädiktivität und die Erfassung des genotoxischen Potentials bereits in der frühen Phase der Arzneimittelentwicklung ab. Die high content imaging (HCI)-Technologie offeriert einen Ansatz zur Verbesserung des Durchsatzes verglichen mit der Standardtestbatterie. Zusätzlich hat ein Zell-basiertes Modell den Vorteil Daten relativ schnell bei gleichzeitig geringem Bedarf an Substanzmenge zu generieren. Demzufolge ermöglichen HCI-basierte Testsysteme eine Prüfung in der frühen Phase der pharmazeutischen Arzneimittelentwicklung. Das Ziel dieser Studie ist die Entwicklung eines neuen, spezifischen und sensitiven HCI-basierten Testsytems für Genotoxine und Progenotoxine in vitro unter Verwendung von HepG2-Zellen gewesen. Aufgrund ihrer begrenzten metabolischen Kapazität wurde ein kombiniertes System bestehend aus HepG2-Zellen und einem metabolischen Aktivierungssystem zur Testung progenotoxischer Substanzen etabliert. Basierend auf einer vorherigen Genomexpressionsprofilierung (Boehme et al., 2011) und einer Literaturrecherche wurden die folgenden neun unterschiedlichen Proteine der DNA-Schadensantwort als putative Marker der Substanz-induzierten Genotoxizität ausgewählt: p-p53 (Ser15), p21, p-H2AX (Ser139), p-Chk1 (Ser345) p-ATM (Ser1981), p-ATR (Ser428), p-CDC2 (Thr14/Tyr15), GADD45A und p-Chk2 (Thr68). Die Expression bzw. Aktivierung dieser Proteine wurde 48 h nach Behandlung mit den (pro-) genotoxischen Substanzen (Cyclophosphamid, 7,12-Dimethylbenz[a]anthracen, Aflatoxin B1, 2-Acetylaminofluoren, Methylmethansulfonat, Actinomycin D, Etoposid) und den nicht-genotoxischen Substanzen (D-Mannitol, Phenforminhydrochlorid, Progesteron) unter Verwendung der HCI-Technologie ermittelt. Die beste Klassifizierung wurde bei Verwendung der folgenden fünf der ursprünglichen neun putativen Markerproteine erreicht: p-p53 (Ser15), p21, p-H2AX (Ser139), p-Chk1 (Ser345) und p-ATM (Ser1981). In einem zweiten Teil dieser Arbeit wurden die fünf ausgewählten Proteine mit Substanzen, welche von dem European Centre for the Validation of Alternative Methods (ECVAM) zur Beurteilung der Leistung neuer oder modifizierter in vitro Genotoxizitätstests empfohlen sind, getestet. Dieses neue Testsystem erzielte eine Sensitivität von 80 % und eine Spezifität von 86 %, was in einer Prädiktivität von 84 % resultierte. Der synergetische Effekt dieser fünf Proteine ermöglicht die Identifizierung von genotoxischen Substanzen, welche DNA-Schädigungen durch eine Vielzahl von unterschiedlichen Mechanismen induzieren, mit einem hohen Erfolg. Zusammenfassend konnte ein hochprädiktives Prüfungssystem mit metabolischer Aktivierung für ein breites Spektrum potenziell genotoxischer Substanzen generiert werden, welches sich aufgrund des hohen Durchsatzes, des geringen Zeitaufwandes und der geringen Menge benötigter Substanz zur Substanzpriorisierung und -selektion in der Phase der Leitstrukturoptimierung eignet und darüber hinaus mechanistische Hinweise auf die genotoxische Wirkung der Testsubstanz liefert.

Prognosis of patients with HIV-1 infection starting antiretroviral therapy in sub-Saharan Africa: a collaborative analysis of scale-up programmes

Background Prognostic models have been developed for patients infected with HIV-1 who start combination antiretroviral therapy (ART) in high-income countries, but not for patients in sub-Saharan Africa. We developed two prognostic models to estimate the probability of death in patients starting ART in sub-Saharan Africa. Methods We analysed data for adult patients who started ART in four scale-up programmes in Côte d'Ivoire, South Africa, and Malawi from 2004 to 2007. Patients lost to follow-up in the first year were excluded. We used Weibull survival models to construct two prognostic models: one with CD4 cell count, clinical stage, bodyweight, age, and sex (CD4 count model); and one that replaced CD4 cell count with total lymphocyte count and severity of anaemia (total lymphocyte and haemoglobin model), because CD4 cell count is not routinely measured in many African ART programmes. Death from all causes in the first year of ART was the primary outcome. Findings 912 (8·2%) of 11 153 patients died in the first year of ART. 822 patients were lost to follow-up and not included in the main analysis; 10 331 patients were analysed. Mortality was strongly associated with high baseline CD4 cell count (≥200 cells per μL vs <25; adjusted hazard ratio 0·21, 95% CI 0·17–0·27), WHO clinical stage (stages III–IV vs I–II; 3·45, 2·43–4·90), bodyweight (≥60 kg vs <45 kg; 0·23, 0·18–0·30), and anaemia status (none vs severe: 0·27, 0·20–0·36). Other independent risk factors for mortality were low total lymphocyte count, advanced age, and male sex. Probability of death at 1 year ranged from 0·9% (95% CI 0·6–1·4) to 52·5% (43·8–61·7) with the CD4 model, and from 0·9% (0·5–1·4) to 59·6% (48·2–71·4) with the total lymphocyte and haemoglobin model. Both models accurately predict early mortality in patients starting ART in sub-Saharan Africa compared with observed data. Interpretation Prognostic models should be used to counsel patients, plan health services, and predict outcomes for patients with HIV-1 infection in sub-Saharan Africa.

The pulmonary artery catheter: in medio virtus

OBJECTIVE: To clarify the role of the pulmonary artery catheter in the intensive care unit. DATA SOURCES: Recent and relevant literature from MEDLINE and authors' personal databases. STUDY SELECTION: Studies on pulmonary artery catheter use and use of other monitoring devices in critically ill patients. DATA EXTRACTION: Based largely on clinical experience and assessment of the relevant published literature and in response to recent articles attacking the pulmonary artery catheter, we propose that the pulmonary artery catheter is still a valuable tool for the hemodynamic monitoring of patients with complex disease processes in whom the information obtained from the pulmonary artery catheter may influence management. We suggest that there is a need to revisit the basics of hemodynamic management and reassess the way in which the pulmonary artery catheter is used, applying three key principles: correct measurement, correct data interpretation, and correct application. CONCLUSION: The pulmonary artery catheter is still a valuable tool for hemodynamic monitoring when used in selected patients and by physicians adequately trained to correctly interpret and apply the data provided.

Using Single-Case Participatory Action Research as a Methodology to Explore Appalachian Summer Camp Communities

Community educators have long known the value of direct experience in the learning process. Participatory action research extends this philosophy to the realm of research. This article examines the value of involving front line camp staff, members of the camp community in Appalachia as practitioner researchers with university scientists in studying the type and conditions of transformative learning in young adult camp staff. A young adult who was a camp community member assisted the researchers with methodology, data analysis, data interpretation, and dissemination of findings. This resulted in a more accurate, richer, and thicker description of the camp community member’s transformative learning experience. The benefits of involving practitioner researchers are examined, as well as promising practices for conducting participatory action research in community education environments.

EFFECTS OF INFORMATION DISPLAY ON THE CONSTRUCTION OF CLINICIAN MENTAL MODELS

Objective: To determine how a clinician’s background knowledge, their tasks, and displays of information interact to affect the clinician’s mental model. Design: Repeated Measure Nested Experimental Design Population, Sample, Setting: Populations were gastrointestinal/internal medicine physicians and nurses within the greater Houston area. A purposeful sample of 24 physicians and 24 nurses were studied in 2003. Methods: Subjects were randomized to two different displays of two different mock medical records; one that contained highlighted patient information and one that contained non-highlighted patient information. They were asked to read and summarize their understanding of the patients aloud. Propositional analysis was used to understand their comprehension of the patients. Findings: Different mental models were found between physicians and nurses given the same display of information. The information they shared was very minor compared to the variance in their mental models. There was additionally more variance within the nursing mental models than the physician mental models given different displays of the same information. Statistically, there was no interaction effect between the display of information and clinician type. Only clinician type could account for the differences in the clinician comprehension and thus their mental models of the cases. Conclusion: The factors that may explain the variance within and between the clinician models are clinician type, and only in the nursing group, the use of highlighting.

Resolving diffusion in clay minerals at different time scales: Combination of experimental and modeling approaches

Since no single experimental or modeling technique provides data that allow a description of transport processes in clays and clay minerals at all relevant scales, several complementary approaches have to be combined to understand and explain the interplay between transport relevant phenomena. In this paper molecular dynamics simulations (MD) were used to investigate the mobility of water in the interlayer of montmorillonite (Mt), and to estimate the influence of mineral surfaces and interlayer ions on the water diffusion. Random Walk (RW) simulations based on a simplified representation of pore space in Mt were used to estimate and understand the effect of the arrangement of Mt particles on the meso- to macroscopic diffusivity of water. These theoretical calculations were complemented with quasielastic neutron scattering (QENS) measurements of aqueous diffusion in Mt with two pseudo-layers of water performed at four significantly different energy resolutions (i.e. observation times). The size of the interlayer and the size of Mt particles are two characteristic dimensions which determine the time dependent behavior of water diffusion in Mt. MD simulations show that at very short time scales water dynamics has the characteristic features of an oscillatory motion in the cage formed by neighbors in the first coordination shell. At longer time scales, the interaction of water with the surface determines the water dynamics, and the effect of confinement on the overall water mobility within the interlayer becomes evident. At time scales corresponding to an average water displacement equivalent to the average size of Mt particles, the effects of tortuosity are observed in the meso- to macroscopic pore scale simulations. Consistent with the picture obtained in the simulations, the QENS data can be described using a (local) 3D diffusion at short observation times, whereas at sufficiently long observation times a 2D diffusive motion is clearly observed. The effects of tortuosity measured in macroscopic tracer diffusion experiments are in qualitative agreement with RW simulations. By using experimental data to calibrate molecular and mesoscopic theoretical models, a consistent description of water mobility in clay minerals from the molecular to the macroscopic scale can be achieved. In turn, simulations help in choosing optimal conditions for the experimental measurements and the data interpretation. (C) 2014 Elsevier B.V. All rights reserved.

Prevalence and risk factors for polyomavirus reactivation in solid-organ transplantation

Background. Polyomavirus reactivation is common in solid-organ transplant recipients who are given immunosuppressive medications as standard treatment of care. Previous studies have shown that polyomavirus infection can lead to allograft failure in as many as 45% of the affected patients. Hypothesis. Ubiquitous polyomaviruses when reactivated by post-transplant immunosuppressive medications may lead to impaired renal function and possibly lower survival prospects. Study Overview. Secondary analysis of data was conducted on a prospective longitudinal study of subjects who were at least 18 years of age and were recipients of liver and/or kidney transplant at Mayo Clinic Scottsdale, Arizona. Methods. DNA extractions of blinded urine and blood specimens of transplant patients collected at Mayo Clinic during routine transplant patient visits were performed at Baylor College of Medicine using Qiagen kits. Virologic assays included testing DNA samples for specific polyomavirus sequences using QPCR technology. De-identified demographic and clinical patient data were merged with laboratory data and statistical analysis was performed using Stata10. Results. 76 patients enrolled in the study were followed for 3.9 years post transplantation. The prevalence of BK virus and JC virus urinary excretion was 30% and 28%. Significant association was observed between JC virus excretion and kidney as the transplanted organ (P = 0.039, Pearson Chi-square test). The median urinary JCV viral loads were two logs higher than those of BKV. Patients that excreted both BKV and JCV appeared to have the worst renal function with a mean creatinine clearance value of 71.6 millimeters per minute. A survival disadvantage was observed for dual shedders of BKV and JCV, log-rank statistics, p = 0.09; 2/5 dual-shedders expired during the study period. Liver transplant and male sex were determined to be potential risk factors for JC virus activation in renal and liver transplant recipients. All patients tested negative for SV40 and no association was observed between polyomavirus excretion and type of immunosuppressive medication (tacrolimus, mycophenolate mofetil, cyclosporine and sirolimus). Conclusions. Polyomavirus reactivation was common after solid-organ transplantation and may be associated with impaired renal function. Male sex and JCV infection may be potential risk factors for viral reactivation; findings should be confirmed in larger studies.^

Capital extranjero y agroindustria : Notas para una discusión sobre los cambios en la burguesía vitivinícola de Argentina a partir de la década del '90

Se propone problematizar cómo afectan a la burguesía vitivinícola de Argentina los cambios producidos en la actividad a partir de la década de los '90, en el marco de los procesos de globalización. Una de las conclusiones principales es que, aunque el ingreso de capitales extranjeros a la actividad vitivinícola ha sido importante, la burguesía cuyos capitales son nacionales y/o locales logra conservar posiciones no desventajosas en la estructura económica de esta agroindustria. Se trabajó principalmente con fuentes estadísticas de organismos oficiales; y con datos obtenidos de páginas web de las empresas, de consultoras especializadas y de entrevistas a informantes calificados. Asimismo, se realizó una exhaustiva revisión bibliográfica sobre la temática