Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estilo de liderança e stress: uma pesquisa em escolas estaduais de ensino fundamental

This survey attempted to find out whether or not the management styles adopted by schools can be associated with teacher stress. The study considered 175 teachers working with 1st‑to 4th grades in twelve public schools. The instruments first identified the leadership style predominant in the schools, then sought to identify the presence of stress in the teachers. Although stress was present in the majority of the teachers, an association with specific management styles could not be confirmed. This can be linked to the fact that the stress was already present in the teachers and did not allow the identification of additional influence by the schools’ leadership style

A estética da imagem na TV digital

This text reflects on the techniques and the process of image production and its artistic composition to digital television in high defini- tion, whereas the 4:3 and 16:9 formats will exist until shutdown of the analog signal. Within this period, consumers of television programming that have analog receivers will continue to see the images in 4:3 format. That fact determines that the productions in high definition, while capturing images with larger viewing area and have high contrast ratio (>1000:1) must be main- tain the elements of visual storytelling within the smallest area and with the contrast ratio of the analog tv (30:1), at the risk of distorting visually the messages produced by the directors.

Longitudinal outcomes of high-risk human papillomavirus (HPV) infections as competing-risks events following cervical HPV test at baseline visit in the *NIS-LAMS** cohort

Background: The complex natural history of human papillomavirus (HPV) infections following a single HPV test can be modeled as competing-risks events (i.e., no-, transient- or persistent infection) in a longitudinal setting. The covariates associated with these compet ng events have not been previously assessed using competing-risks regression models. Objectives: To gain further insights in the outcomes of cervical HPV infections, we used univariate- and multivariate competing-risks regression models to assess the covariaies associated with these competing events. Study Design and Methods: Covariates associated with three competing outcomes (no-, transient- or persistent HR-HPV infection) were analysed in a sub-cohort of 1,865 women prospectively followed-up in the NIS (n = 3,187) and LAMS Study (n = 12,114). Results: In multivariate competing-risks models (with two other outcomes as competing events), permanently HR-HPV negative outcome was significantly predicted only by the clearance of ASCUS+Pap during FU, while three independent covariates predicted transient HR-HPV infections: i) number of recent (< 12 months) sexual partners (risk increased), ii) previous Pap screening history (protective), and history of previous CIN (increased risk). The two most powerful predictors of persistent HR-HPV infections were persistent ASCUS+Pap (risk increased), and previous Pap screening history (protective). In pair-wise comparisons, number of recent sexual partners and previous CIN history increase the probability of transient HR-HPV infection against the HR-HPV negative competing event, while previous Pap screening history is protective. Persistent ASCUS+Pap during FU and no previous Pap screening history are significantly associated with the persistent HR-HPV outcome (compared both with i) always negative, and ii) transient events), whereas multiparity is protective. Conclusions: Different covariates are associated with the three main outcomes of cervical HPV infections. The most significant covariates of each competing events are probably distinct enough to enable constructing of a risk-profile for each main outcome.

Covariates of high-risk human papillomavirus (HPV) infections are distinct for incident CIN1, CIN2 and CIN3 as disclosed by competing-risks regression models

Background: In addition to the oncogenic human papillomavirus (HPV), several cofactors are needed in cervical carcinogenesis, but whether the HPV covariates associated with incident i) CIN1 are different from those of incident ii) CIN2 and iii) CIN3 needs further assessment. Objectives: To gain further insights into the true biological differences between CIN1, CIN2 and CIN3, we assessed HPV covariates associated with incident CIN1, CIN2, and CIN3. Study Design and Methods: HPV covariates associated with progression to CIN1, CIN2 and CIN3 were analysed in the combined cohort of the NIS (n = 3,187) and LAMS study (n = 12,114), using competing-risks regression models (in panel data) for baseline HR-HPV-positive women (n = 1,105), who represent a sub-cohort of all 1,865 women prospectively followed-up in these two studies. Results: Altogether, 90 (4.8%), 39 (2.1%) and 14 (1.4%) cases progressed to CIN1, CIN2, and CIN3, respectively. Among these baseline HR-HPV-positive women, the risk profiles of incident GIN I, CIN2 and CIN3 were unique in that completely different HPV covariates were associated with progression to CIN1, CIN2 and CIN3, irrespective which categories (non-progression, CIN1, CIN2, CIN3 or all) were used as competing-risks events in univariate and multivariate models. Conclusions: These data confirm our previous analysis based on multinomial regression models implicating that distinct covariates of HR-HPV are associated with progression to CIN1, CIN2 and CIN3. This emphasises true biological differences between the three grades of GIN, which revisits the concept of combining CIN2 with CIN3 or with CIN1 in histological classification or used as a common end-point, e.g., in HPV vaccine trials.

Ecofisiología planctónica

[ES] El grupo de investigación en Ecofisiología Planctónica (GEP), de la Universidad de Las Palmas de Gran Canaria, tiene como objetivos los estudios de crecimiento y del metabolismo respiratorio y excretor en zooplancton, fitoplancton, bacterias y macroalgas. A partir de estas medidas primarias, el GEP puede calcular los flujos de carbono y nitrógeno oceánicos así como la eficiencia en la retención de nutrientes y el metabolismo del oceáno profundo. Estas medidas constituyen parámetros de gran importancia para el desarrollo de modelos precisos de predicción de los posibles cambios futuros en el planeta debidos al Cambio Climático. La principal premisa en la que se apoyan las investigaciones del grupo es que la bioquímica enzimática controla la fisiología de los organísmos, lo que produce un fuerte impacto en la ecología y la química oceánica. El GEP, trata también de describir los procesos fisiológicos del océano a través del uso de modelos matemáticos, para ello es necesario realizar experimentos de laboratorio así como muestreos de campo para determinar los parámetros cinéticos que controlan las reacciones que regulan la fisiología de los organísmos marinos. Asociado con GEP la empresa de base Técnológica BioceanSolutions, dedica también gran parte de sus esfuerzos en mejorar la metodología existente así como en desarrollar nuevos métodos enzimáticos, que nos permitan conocer y controlar el estado de salud de las comunidades marinas.

Pattern formation for a reaction-diffusion system: Catalytic-dependent diffusion coefficients

[ES]Se considera un modelo de reacción-difusión para dos reactantes en presencia de un tercero, que actúa de catalizador. La escala temporal para el catalizador se compara con la de los reactantes y los coeficientes de difusión dependen solamente de la concentración en el estado de equilibrio del catalizador. Se realizan experimentos para diferentes cinéticas

Chemistry of Fe(II) in the presence of organic exudates from phytoplankton and of copper in seawater

Programa de doctorado de Oceanografía ; 2006-2008

Arresto e fermo: Prassi applicative e prospettive di riforma

Il presente lavoro ha ad oggetto l’esame della disciplina dell’arresto in flagranza e del fermo di indiziato di delitto: istituti profondamente “utili” e “d’impatto” (anche mass-mediatico) perché ontologicamente tesi, soprattutto il primo, all’immediata repressione del fenomeno criminale. Scopo e ragione di questo studio, è dunque l’individuazione di altre e più profonde finalità di tali istituti, passando per una piena comprensione del ruolo loro assegnato nel vigente impianto codicistico. La ricerca, dunque, si è sviluppata lungo tre direttrici, ciascuna rappresentata – anche dal punto di vista grafico-strutturale – nelle tre parti cin cui è diviso l’elaborato finale e ciascuna singolarmente riferibile, in un’immaginaria linea del tempo, allo ieri (e ai principi), all’oggi e al domani della disciplina delle misure coercitive di polizia giudiziaria. Nella prima parte, infatti, partendo dall’analisi storica degli istituti in esame, si è proceduto all’esame della disciplina e della giurisprudenza costituzionale in tema di strumenti di polizia giudiziari provvisoriamente limitativi della libertà personale; l’obiettivo primo di tale approfondimento, cui poi sarà informato l’analisi della dinamica degli istituti, è proprio l’individuazione delle finalità – conformi a Costituzione – dell’arresto e del fermo di indiziato di delitto. Seguirà l’analisi del concetto di libertà personale, e dei margini consentiti per la sua limitazione, in seno al sistema della Convenzione europea per la salvaguardia dei diritti dell’uomo. La seconda parte contiene un’analisi critica degli istituti dell’arresto in flagranza, del fermo di indiziato di delitto e dell’arresto urgente a fini estradizionale. Infine, la terza e ultima parte ha ad oggetto l’ulteriore di linea di ricerca che si è sviluppata a mo’ di conclusione delle predette analisi, riguardante la possibilità di utilizzare lo strumento del fermo, ampliandone le maglie applicative, come viatico per l’introduzione del contraddittorio anticipato rispetto all’applicazione delle misure cautelari personali

Synaptic regulation of spike firing in interneurons of the striatum in vivo

The striatum, the major input nucleus of the basal ganglia, is numerically dominated by a single class of principal neurons, the GABAergic spiny projection neuron (SPN) that has been extensively studied both in vitro and in vivo. Much less is known about the sparsely distributed interneurons, principally the cholinergic interneuron (CIN) and the GABAergic fast-spiking interneuron (FSI). Here, we summarize results from two recent studies on these interneurons where we used in vivo intracellular recording techniques in urethane-anaesthetized rats (Schulz et al., J Neurosci 31[31], 2011; J Physiol, in press). Interneurons were identified by their characteristic responses to intracellular current steps and spike waveforms. Spontaneous spiking contained a high proportion (~45%) of short inter-spike intervals (ISI) of <30 ms in FSIs, but virtually none in CINs. Spiking patterns in CINs covered a broad spectrum ranging from regular tonic spiking to phasic activity despite very similar unimodal membrane potential distributions across neurons. In general, phasic spiking activity occurred in phase with the slow ECoG waves, whereas CINs exhibiting tonic regular spiking were little affected by afferent network activity. In contrast, FSIs exhibited transitions between Down and Up states very similar to SPNs. Compared to SPNs, the FSI Up state membrane potential was noisier and power spectra exhibited significantly larger power at frequencies in the gamma range (55-95 Hz). Cortical-evoked inputs had faster dynamics in FSIs than SPNs and the membrane potential preceding spontaneous spike discharge exhibited short and steep trajectories, suggesting that fast input components controlled spike output in FSIs. Intrinsic resonance mechanisms may have further enhanced the sensitivity of FSIs to fast oscillatory inputs. Induction of an activated ECoG state by local ejection of bicuculline into the superior colliculus, resulted in increased spike frequency in both interneuron classes without changing the overall distribution of ISIs. This manipulation also made CINs responsive to a light flashed into the contralateral eye. Typically, the response consisted of an excitation at short latency followed by a pause in spike firing, via an underlying depolarization-hyperpolarization membrane sequence. These results highlight the differential sensitivity of striatal interneurons to afferent synaptic signals and support a model where CINs modulate the striatal network in response to salient sensory bottom-up signals, while FSIs serve gating of top-down signals from the cortex during action selection and reward-related learning.

L’industrie cinématographique du Cameroun : évaluation et perspectives

L’industrie cinématographique africaine d’aujourd’hui connaît de grandes avancées dans de nombreux pays d’Afrique. Seulement, autant certains pays africains connaissent de grandes avancées, autant d’autres pays voient leur industrie cinématographique traîner le pas. Le Cameroun est un exemple qui illustre à souhait ces pays qui sont à la traîne. Deux constats s’imposent à nous dans ce cas d’espèce. D’un côté, le Ministère de la Culture semble s’essouffler par le rôle qui lui incombe. De ce fait, il est de moins en moins actif et très peu représenté sur le terrain. De l’autre côté, nous observons çà et là de multiples activités. Des festivals, de long et court métrages organisés par des camerounais, ainsi que des rencontres cinématographiques mises sur pied en partenariat avec les représentations culturelles de pays étrangers en présence sur le territoire. Ces initiatives diverses malgré l’atmosphère peu favorable du pays parviennent à impulser une certaine dynamique. Notons tout de même que ces actions restent cantonnées dans les deux principales villes que sont Yaoundé et Douala. Après ce bref aperçu du tableau cinématographique camerounais, deux questions s’imposent à nous : Quelle appréciation peut-on faire du cinéma au Cameroun aujourd’hui ? Quel avenir pour celui-ci ? Telles sont les deux préoccupations auxquelles nous essaierons d’apporter quelques éléments de réponses dans cette étude. // Mots clés : cinéma, Cameroun, bilan, perspectives, initiatives, industrie cinématographique.

Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors

BACKGROUND & AIMS Sporadic pancreatic neuroendocrine tumors (pNETs) are rare and genetically heterogeneous. Chromosome instability (CIN) has been detected in pNETs from patients with poor outcomes, but no specific genetic factors have been associated with CIN. Mutations in death domain-associated protein gene (DAXX) or ATR-X gene (ATRX) (which both encode proteins involved in chromatin remodeling) have been detected in 40% of pNETs, in association with activation of alternative lengthening of telomeres. We investigated whether loss of DAXX or ATRX, and consequent alternative lengthening of telomeres, are related to CIN in pNETs. We also assessed whether loss of DAXX or ATRX is associated with specific phenotypes of pNETs. METHODS We collected well-differentiated primary pNET samples from 142 patients at the University Hospital Zurich and from 101 patients at the University Hospital Bern (both located in Switzerland). Clinical follow-up data were obtained for 149 patients from general practitioners and tumor registries. The tumors were reclassified into 3 groups according to the 2010 World Health Organization classification. Samples were analyzed by immunohistochemistry and telomeric fluorescence in situ hybridization. We correlated loss of DAXX, or ATRX, expression, and activation of alternative lengthening of telomeres with data from comparative genomic hybridization array studies, as well as with clinical and pathological features of the tumors and relapse and survival data. RESULTS Loss of DAXX or ATRX protein and alternative lengthening of telomeres were associated with CIN in pNETs. Furthermore, loss of DAXX or ATRX correlated with tumor stage and metastasis, reduced time of relapse-free survival, and decreased time of tumor-associated survival. CONCLUSIONS Loss of DAXX or ATRX is associated with CIN in pNETs and shorter survival times of patients. These results support the hypothesis that DAXX- and ATRX-negative tumors are a more aggressive subtype of pNET, and could lead to identification of strategies to target CIN in pancreatic tumors.

MODELING SPORADIC TUMOR FORMATION DRIVEN BY TELOMERE DYSFUNCTION IN THE GASTROINTESTINAL TRACT

Colorectal cancer is a complex disease that is thought to arise when cells accumulate mutations that allow for uncontrolled growth. There are several recognized mechanisms for generating such mutations in sporadic colon cancer; one of which is chromosomal instability (CIN). One hypothesized driver of CIN in cancer is the improper repair of dysfunctional telomeres. Telomeres comprise the linear ends of chromosomes and play a dual role in cancer. Its length is maintained by the ribonucleoprotein, telomerase, which is not a normally expressed in somatic cells and as cells divide, telomeres continuously shorten. Critically shortened telomeres are considered dysfunctional as they are recognized as sites of DNA damage and cells respond by entering into replicative senescence or apoptosis, a process that is p53-dependent and the mechanism for telomere-induced tumor suppression. Loss of this checkpoint and improper repair of dysfunctional telomeres can initiate a cycle of fusion, bridge and breakage that can lead to chromosomal changes and genomic instability, a process that can lead to transformation of normal cells to cancer cells. Mouse models of telomere dysfunction are currently based on knocking out the telomerase protein or RNA component; however, the naturally long telomeres of mice require multiple generational crosses of telomerase null mice to achieve critically short telomeres. Shelterin is a complex of six core proteins that bind to telomeres specifically. Pot1a is a highly conserved member of this complex that specifically binds to the telomeric single-stranded 3’ G-rich overhang. Previous work in our lab has shown that Pot1a is essential for chromosomal end protection as deletion of Pot1a in murine embryonic fibroblasts (MEFs) leads to open telomere ends that initiate a DNA damage response mediated by ATR, resulting in p53-dependent cellular senescence. Loss of Pot1a in the background of p53 deficiency results in increased aberrant homologous recombination at telomeres and elevated genomic instability, which allows Pot1a-/-, p53-/- MEFs to form tumors when injected into SCID mice. These phenotypes are similar to those seen in cells with critically shortened telomeres. In this work, we created a mouse model of telomere ysfunction in the gastrointestinal tract through the conditional deletion of Pot1a that recapitulates the microscopic features seen in severe telomere attrition. Combined intestinal loss of Pot1a and p53 lead to formation of invasive adenocarcinomas in the small and large intestines. The tumors formed with long latency, low multiplicity and had complex genomes due to chromosomal instability, features similar to those seen in sporadic human colorectal cancers. Taken together, we have developed a novel mouse model of intestinal tumorigenesis based on genomic instability driven by telomere dysfunction.

The performance of human papillomavirus high-risk DNA testing in the screening and diagnostic settings.

OBJECTIVE: We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older. MATERIALS AND METHODS: Screening (n=835) and diagnosis (n=518) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection. We compared the Hybrid Capture II (HCII) test result with the worst histologic report. We used cervical intraepithelial neoplasia (CIN) 2/3 or worse as the reference of disease. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic (ROC) curves, and areas under the ROC curves for the HCII test. We also considered alternative strategies, including Papanicolaou smear, a combination of Papanicolaou smear and the HCII test, a sequence of Papanicolaou smear followed by the HCII test, and a sequence of the HCII test followed by Papanicolaou smear. RESULTS: For the screening group, the sensitivity was 0.69 and the specificity was 0.93; the area under the ROC curve was 0.81. The LR+ and LR- were 10.24 and 0.34, respectively. For the diagnosis group, the sensitivity was 0.88 and the specificity was 0.78; the area under the ROC curve was 0.83. The LR+ and LR- were 4.06 and 0.14, respectively. Sequential testing showed little or no improvement over the combination testing. CONCLUSIONS: The HCII test in the screening group had a greater LR+ for the detection of CIN 2/3 or worse. HCII testing may be an additional screening tool for cervical cancer in women 30 years and older.

Influence of the background wind on the local soil moisture-precipitation feedback

The importance of soil moisture anomalies on airmass convection over semiarid regions has been recognized in several studies. The underlying mechanisms remain partly unclear. An open question is why wetter soils can result in either an increase or a decrease of precipitation (positive or negative soil moisture–precipitation feedback, respectively). Here an idealized cloud-resolving modeling framework is used to explore the local soil moisture–precipitation feedback. The approach is able to replicate both positive and negative feedback loops, depending on the environmental parameters. The mechanism relies on horizontal soil moisture variations, which may develop and intensify spontaneously. The positive expression of the feedback is associated with the initiation of convection over dry soil patches, but the convective cells then propagate over wet patches where they strengthen and preferentially precipitate. The negative feedback may occur when the wind profile is too weak to support the propagation of convective features from dry to wet areas. Precipitation is then generally weaker and falls preferentially over dry patches. The results highlight the role of the midtropospheric flow in determining the sign of the feedback. A key element of the positive feedback is the exploitation of both low convective inhibition (CIN) over dry patches (for the initiation of convection) and high CAPE over wet patches (for the generation of precipitation).