Stratigraphy of the Cenomanian-Turonian Oceanic Anoxic Event OAE2 in shallow shelf sequences of NE Egypt

Two shallow water late Cenomanian to early Turonian sequences of NE Egypt have been investigated to evaluate the response to OAE2. Age control based on calcareous nannoplankton, planktic foraminifera and ammonite biostratigraphies integrated with delta(13)C stratigraphy is relatively good despite low diversity and sporadic occurrences. Planktic and benthic foraminiferal faunas are characterized by dysoxic, brackish and mesotrophic conditions, as indicated by low species diversity, low oxygen and low salinity tolerant planktic and benthic species, along with oyster-rich limestone layers. In these subtidal to inner neritic environments the OAE2 delta(13)C excursion appears comparable and coeval to that of open marine environments. However, in contrast to open marine environments where anoxic conditions begin after the first delta(13)C peak and end at or near the Cenomanian-Turonian boundary, in shallow coastal environments anoxic conditions do not appear until the early Turonian. This delay in anoxia appears to be related to the sea-level transgression that reached its maximum in the early Turonian, as observed in shallow water sections from Egypt to Morocco. (C) 2011 Elsevier Ltd. All rights reserved.

Assessment of early-stage optic nerve invasion in retinoblastoma using high-resolution 1.5 Tesla MRI with surface coils: a multicentre, prospective accuracy study with histopathological correlation.

OBJECTIVES: To assess the accuracy of high-resolution (HR) magnetic resonance imaging (MRI) in diagnosing early-stage optic nerve (ON) invasion in a retinoblastoma cohort. METHODS: This IRB-approved, prospective multicenter study included 95 patients (55 boys, 40 girls; mean age, 29 months). 1.5-T MRI was performed using surface coils before enucleation, including spin-echo unenhanced and contrast-enhanced (CE) T1-weighted sequences (slice thickness, 2 mm; pixel size <0.3 × 0.3 mm(2)). Images were read by five neuroradiologists blinded to histopathologic findings. ROC curves were constructed with AUC assessment using a bootstrap method. RESULTS: Histopathology identified 41 eyes without ON invasion and 25 with prelaminar, 18 with intralaminar and 12 with postlaminar invasion. All but one were postoperatively classified as stage I by the International Retinoblastoma Staging System. The accuracy of CE-T1 sequences in identifying ON invasion was limited (AUC = 0.64; 95 % CI, 0.55 - 0.72) and not confirmed for postlaminar invasion diagnosis (AUC = 0.64; 95 % CI, 0.47 - 0.82); high specificities (range, 0.64 - 1) and negative predictive values (range, 0.81 - 0.97) were confirmed. CONCLUSION: HR-MRI with surface coils is recommended to appropriately select retinoblastoma patients eligible for primary enucleation without the risk of IRSS stage II but cannot substitute for pathology in differentiating the first degrees of ON invasion. KEY POINTS: • HR-MRI excludes advanced optic nerve invasion with high negative predictive value. • HR-MRI accurately selects patients eligible for primary enucleation. • Diagnosis of early stages of optic nerve invasion still relies on pathology. • Several physiological MR patterns may mimic optic nerve invasion.

Outcome of smoking cessation counselling of HIV-positive persons by HIV care physicians.

OBJECTIVES: Smoking is the most prevalent modifiable risk factor for cardiovascular diseases among HIV-positive persons. We assessed the effect on smoking cessation of training HIV care physicians in counselling. METHODS: The Swiss HIV Cohort Study (SHCS) is a multicentre prospective observational database. Our single-centre intervention at the Zurich centre included a half day of standardized training for physicians in counselling and in the pharmacotherapy of smokers, and a physicians' checklist for semi-annual documentation of their counselling. Smoking status was then compared between participants at the Zurich centre and other institutions. We used marginal logistic regression models with exchangeable correlation structure and robust standard errors to estimate the odds of smoking cessation and relapse. RESULTS: Between April 2000 and December 2010, 11 056 SHCS participants had 121 238 semi-annual visits and 64 118 person-years of follow-up. The prevalence of smoking decreased from 60 to 43%. During the intervention at the Zurich centre from November 2007 to December 2009, 1689 participants in this centre had 6068 cohort visits. These participants were more likely to stop smoking [odds ratio (OR) 1.23; 95% confidence interval (CI) 1.07-1.42; P=0.004] and had fewer relapses (OR 0.75; 95% CI 0.61-0.92; P=0.007) than participants at other SHCS institutions. The effect of the intervention was stronger than the calendar time effect (OR 1.19 vs. 1.04 per year, respectively). Middle-aged participants, injecting drug users, and participants with psychiatric problems or with higher alcohol consumption were less likely to stop smoking, whereas persons with a prior cardiovascular event were more likely to stop smoking. CONCLUSIONS: An institution-wide training programme for HIV care physicians in smoking cessation counselling led to increased smoking cessation and fewer relapses.

Retinal vessel oxygen saturation and its correlation with structural changes in retinitis pigmentosa.

PURPOSE: To study the influence of retinal structural changes on oxygen saturation in retinitis pigmentosa (RP) patients. METHODS: Oximetry measurements were performed on 21 eyes of 11 RP patients and compared to 24 eyes of 12 controls. Retinal oxygen saturation was measured in all major retinal arterioles (A-SO₂) and venules (V-SO₂) with an oximetry unit of the retinal vessel analyser (IMEDOS Systems UG, Jena, Germany). Oximetry data were compared with morphological changes measured by Cirrus optical coherence tomography (OCT) (Carl Zeiss Meditec, Dublin, CA, USA, macular thickness protocol). RESULTS: In RP patients, the retinal A-SO₂ and V-SO₂ levels were higher at 99.3% (p = 0.001, anova based on mixed-effects model) and 66.8% (p < 0.001), respectively, and the difference between the two (A-V SO₂) was lower at 32.5% (p < 0.001), when compared to the control group (92.4%; 54.0%; 38.4%, respectively). With the RP group, the A-V SO₂ correlated positively, not only with central macular thickness, but also with retinal thickness, in zones 2 and 3 (p = 0.006, p = 0.007, p = 0.014). CONCLUSION: These data indicate that oxygen metabolism was altered in RP patients. Based on our preliminary results, retinal vessel saturation correlated with structural alterations in RP. This method could be valuable in monitoring disease progression and evaluating a potential therapeutic response.

Clinical growth rate of acoustic schwannomas: correlation with the growth fraction as defined by the monoclonal antibody ki-67.

The growth rate of acoustic tumors, although slow, varies widely. There may be a continuous spectrum or distinct groups of tumor growth rates. Clinical, audiologic, and conventional histologic tests have failed to shed any light on this problem. Modern immunohistochemical methods may stand a better chance. The Ki-67 monoclonal antibody stains proliferating cells and is used in this study to investigate the growth fraction of 13 skull base schwannomas. The acoustic tumors can be divided into two different growth groups, one with a rate five times the other. The literature is reviewed to see if this differentiation is borne out by the radiologic studies. Distinct growth rates have been reported: one very slow, taking 50 years to reach 1 cm in diameter, a second rate with a diameter increase of 0.2 cm/year, and a third rate five times the second, with a 1.0 cm increase in diameter per year. A fourth group growing at 2.5 cm/year is postulated, but these tumors cannot be followed for long radiologically, since symptoms demand surgical intervention. The clinical implications of these separate growth rates are discussed.

18F-fluorodeoxyglucose PET/CT findings in pleural effusions of patients with known cancer. A cytopathological correlation.

Aim: Pleural effusion is common in cancer patients and to determine its malignant origin is of huge clinical significance. PET/CT with 18F-FDG is of diagnostic value in staging and follow-up, but its ability to differentiate between malignant and benign effusions is not precisely known. Patients, methods: We examined 50 PET/CT from 47 patients (29 men, 18 women, 60±16 years) with pleural effusion and known cancer (24 NSCLC, 7 lymphomas, 5 breasts, 4 GIST, 3 mesotheliomas, 2 head and neck, 2 malignant teratoma, 1 colorectal, 1 oesophageal, 1 melanoma) for FDG uptake in the effusions using SUVmax. This was correlated to cytopathology performed after a median of 21 days (interquartile range -3 to 23), which included pH, relative distribution (macrophages, neutrophils, eosinophils, basophils, lymphocytes, plasmocytes), and absolute cell count. Results: Malignant cells were found in 17 effusions (34%) (6 NSCLC, 5 lymphomas, 2 breasts, 2 mesotheliomas, 2 malignant teratomas). SUV in malignant effusions were higher than in benign ones [3.7 (95%CI 1.8-5.6) vs. 1.7 g/ml (1.5-1.9), p = 0.001], with a correlation between malignant effusion and SUV (Spearman coefficient r = 0.50, p = 0.001), but not with other cytopathological or radiological parameters (ROC area 0.83±0.06). Using a 2.2-mg/l SUV threshold, 12 PET/CT studies were positive and 38 negative with sensitivity, specificity, positive and negative predictive values of 53%, 91%, 75% and 79%, respectively. For NSCLC only (n = 24), ROC area was 0.95±0.04, 7 studies were positive and 17 negative with a sensitivity, specificity, positive and negative predictive values of 83%, 89%, 71 and 94%, respectively. Conclusion: PET/CT may help to differentiate the malignant or benign origin of a pleural effusion with a high specificity in patients with known cancer, in particular NSCLC.

Correlation between microtensile bond strength data and clinical outcome of Class V restorations.

OBJECTIVE: To determine if the results of resin-dentin microtensile bond strength (µTBS) is correlated with the outcome parameters of clinical studies on non-retentive Class V restorations. METHODS: Resin-dentin µTBS data were obtained from one test center; the in vitro tests were all performed by the same operator. The µTBS testing was performed 8h after bonding and after 6 months of storing the specimens in water. Pre-test failures (PTFs) of specimens were included in the analysis, attributing them a value of 1MPa. Prospective clinical studies on cervical restorations (Class V) with an observation period of at least 18 months were searched in the literature. The clinical outcome variables were retention loss, marginal discoloration and marginal integrity. Furthermore, an index was formulated to be better able to compare the laboratory and clinical results. Estimates of adhesive effects in a linear mixed model were used to summarize the clinical performance of each adhesive between 12 and 36 months. Spearman correlations between these clinical performances and the µTBS values were calculated subsequently. RESULTS: Thirty-six clinical studies with 15 adhesive/restorative systems for which µTBS data were also available were included in the statistical analysis. In general 3-step and 2-step etch-and-rinse systems showed higher bond strength values than the 2-step/3-step self-etching systems, which, however, produced higher values than the 1-step self-etching and the resin modified glass ionomer systems. Prolonged water storage of specimens resulted in a significant decrease of the mean bond strength values in 5 adhesive systems (Wilcoxon, p<0.05). There was a significant correlation between µTBS values both after 8h and 6 months of storage and marginal discoloration (r=0.54 and r=0.67, respectively). However, the same correlation was not found between µTBS values and the retention rate, clinical index or marginal integrity. SIGNIFICANCE: As µTBS data of adhesive systems, especially after water storage for 6 months, showed a good correlation with marginal discoloration in short-term clinical Class V restorations, longitudinal clinical trials should explore whether early marginal staining is predictive for future retention loss in non-carious cervical restorations.

Correlation of photodynamic activity and fluorescence signaling for free and pegylated mTHPC in mesothelioma xenografts

Rapport de synthèse : Introduction : Les premières applications cliniques de la thérapie photodynamique (PDT) remontent à plus d'une vingtaine d'années. Basée sur l'activation d'un médicament photosensibilisateur par une source lumineuse à une longueur d'onde spécifique, la PDT permet la destruction sélective de tissus contenant le produit actif. Ce procédé a été expérimenté dans le traitement de cancers en raison de la propriété du médicament à se concentrer dans les tumeurs tout en épargnant les structures normales contigües. Cependant, les photosensibilisateurs utilisés jusqu'à ce jour n'ont pas démontré une accumulation exclusive dans les tissus néoplasiques mais également dans les structures saines avoisinantes induisant une destruction tissulaire non sélective. Notamment, d'importantes complications ont été rapportées suite à l'utilisation de la PDT dans la cavité thoracique après la résection de mésothéliomes pleuraux, et ce malgré l'arrivée de photosensibilisateurs de secondes générations. De ce fait, plusieurs études expérimentales ont été menées afin d'améliorer la sélectivité tumorale du médicament en modulant différentes conditions de traitement et en modifiant la structure du photosensibilisateur par pégylation. Le but de cette étude expérimentale est de corréler l'activité photodynamique, la phototoxicité et la distribution du m-tetrahydroxyphenylchlorin (mTHPC) et de sa forme pégylée, le PEG-mTHPC. De ce fait, un modèle de souris nues porteur de xenogreffes de mésothéliome humain a été utilisé pour étudier les deux photosensibilisateurs. De récents travaux avec ce modèle ont montré que la mesure de la concentration tissulaire du mTHPC et de sa forme pégylée par HPLC restait limitée afin de prédire l'activité photodynamique. De ce fait, nous pensons que les mesures de fluorescence peuvent être plus appropriée. Le signalement fluorescent est mesuré dans le tissu tumoral et dans une région contrôle de la peau afin d'étudier la distribution et l'intensité des deux sensibilisateurs. Méthode : Des souris nues (cd1nu/nu mice) de 8 semaines ont été transplantées avec des fragments de mésothéliome malin humain (H-meso-1). Ces derniers ont été obtenus à partir d'une suspension cellulaire. Au moins trois passages ont été faits dans les animaux, avant que le traitement soit initié. Deux groupes de 6 souris chacun ont été utilisés pour l'injection intraveineuse par la queue du mTHPC à 0.15 mg/kg et du PEG-mTHPC à dose équimolaire. Après trois jour, la tumeur ainsi qu'une région contrôle de la cuisse ont été illuminées sur une surface d'un diamètre de 1.2 cm et pendant 133 secondes avec un laser à une longueur d'onde à 652 nm (fluence 20 J/cm2, fluence rate 150 mW/cm2). Les animaux ont été ensuite sacrifiés 72 heures après l'illumination. L'étendue de la nécrose tumorale et de la région contrôle ont été déterminées en aveugle par histomorphometrie par un pathologue (HJA). La fluorescence microscopique a été évaluée dans 12 souris à une concentration de 0.15 et 0.5 mg/kg pour le mTHPC, et à doses équimolaires pour le PEG-mTHPC. Trois animaux ont été injectés avec le mTHPC à 0.15 mg/kg, 3 autres à dose équimolaire avec la forme pégylée et 6 souris avec le mTHPC à 0.5 mg/kg et à dose équimolaire. Les animaux ont été sacrifiés 72 heures après injection. L'intensité fluorescente des sensibilisateurs a été mesurée dans la tumeur et la région contrôle. Suite à cela, les coupes ont été fixées par H&E et superposées aux images fluorescentes, afin de localiser la distribution des deux photosensibilisateurs dans les différents compartiments tissulaires. Six souris transplantées n'ayant ni été injectées avec les sensibilisateurs ou illuminées ont servi de groupe contrôle. Résultats : Trois jours après l'illumination, la PDT provoque une nécrose tumorale de 10 ±5.4 mm2 pour le mTHPC à 0.15mg/kg et 5.2 ± 4.6 mm2 pour sa forme pégylée à dose équimolaire. Cependant, la nécrose tumorale induite par les deux formulations du sensibilisateur est significativement plus élevée que dans le groupe contrôle (0.33 ± 0.58 mm2) (P=0.02). Toutefois, le mTHPC pégylé provoque une photosensibilité cutanée moins importante que la forme non-pegylée. Dans les deux groupes, aucune nécrose n'a été observée dans la cuisse des animaux. Trois jours après l'injection du mTHPC et de la forme pégylée à 0.15 mg/kg, aucune activité fluorescente n'a été détectée. Cependant, à 0.5 mg/kg, la fluorescence microscopique révèle une distribution hétérogène des deux photo-sensibilisateurs dans le tissu tumoral avec une accumulation prédominante dans les régions peri-vasculaires. Les deux médicaments montrent une distribution intracellulaire homogène dans le cytoplasme et une absence de signalement dans le nucleus. La mesure de l'intensité fluorescente du mTHPC à 0.5mg/kg ne montre pas de différence significative entre le tissu tumoral et la région contrôle. Par contre, le PEG-mTHPC montre une intensité fluorescente supérieure dans le tissu tumoral que dans la peau (ratio tumeur- peau 0.94 pour le mTHPC et 1.73 pour le PEG-mTHPC). Conclusion : L'utilisation du mTHPC à 0.15mg/kg induit une nécrose tumorale similaire à celle du PEG-mTHPC à dose équimolaire. Cependant, ce dernier démontre une photo-toxicité plus atténuée de la peau. La fluorescence microscopique permet de localiser les deux sensibilisateurs dans les différents compartiments tissulaires à partir d'une dose de 0.5 mg/kg. Le PEG-mTHPC induit un signalement fluorescent supérieur dans le tissu tumoral par rapport à la peau. La mesure du signalement fluorescent a le potentiel de prédire l'activité photodynamique du mTHPC et de sa forme pégylée dans les xénogreffes de mésothéliome humain dans un modèle de souris nue.

Age-related differences on event-related potentials and brain rhythm oscillations during working memory activation.

Previous functional imaging studies have pointed to the compensatory recruitment of cortical circuits in old age in order to counterbalance the loss of neural efficiency and preserve cognitive performance. Recent electroencephalographic (EEG) analyses reported age-related deficits in the amplitude of an early positive-negative working memory (PN(wm)) component as well as changes in working memory (WM)-load related brain oscillations during the successful performance of the n-back task. To explore the age-related differences of EEG activation in the face of increasing WM demands, we assessed the PN(wm) component area, parietal alpha event-related synchronization (ERS) as well as frontal theta ERS in 32 young and 32 elderly healthy individuals who successfully performed a highly WM demanding 3-back task. PN(wm) area increased with higher memory loads (3- and 2-back > 0-back tasks) in younger subjects. Older subjects reached the maximal values for this EEG parameter during the less WM demanding 0-back task. They showed a rapid development of an alpha ERS that reached its maximal amplitude at around 800 ms after stimulus onset. In younger subjects, the late alpha ERS occurred between 1,200 and 2,000 ms and its amplitude was significantly higher compared with elders. Frontal theta ERS culmination peak decreased in a task-independent manner in older compared with younger cases. Only in younger individuals, there was a significant decrease in the phasic frontal theta ERS amplitude in the 2- and 3-back tasks compared with the detection and 0-back tasks. These observations suggest that older adults display a rapid mobilization of their neural generators within the parietal cortex to manage very low demanding WM tasks. Moreover, they are less able to activate frontal theta generators during attentional tasks compared with younger persons.

A synchronous, middle early Aptian age for the demise of the Helvetic Urgonian platform related to the unfolding oceanic anoxic event 1a ("Selli event")

Un âge synchrone (partie moyenne de l'Aptien inférieur) de l'ennoiement de la plate-forme Urgonienne helvétique en relation avec l'événement océanique anoxique 1a ("événement Selli"). - La fin de la plate-forme urgonienne, calibrée par analyse des isotopes stables du carbone sur roche totale et par biostratigraphie basée sur les ammonites, est datée du milieu de l'Aptien inférieur (Près de la limite des zones weissi et deshayesi). Cet arrêt, synchrone dans des coupes représentatives du domaine helvétique alpin, est un événement environemental majeur renregistré en France, en Espagne, au Protugal, en Oman, au Mexique et dans le domaine Pacifique. En tenant compte des limites de résolution de la biostatrigraphie et des autres techniques de datation, cet épisode semble également être synchrone à l'échelle globale. Pour beaucoup d'auteurs, la disparition de récifs de coraux et de rudistes corrélée à la fin de la sédimentation urgonienne correspond à la mise en place de conditions anoxiques à l'Aptien inférieur. Celles-ci caractérisent un événement d'importance global: l'événement anoxique OAE 1a.

Correlation of CXCL10, tumor necrosis factor receptor type II, and galectin 9 with disease activity in juvenile dermatomyositis.

OBJECTIVE: Juvenile dermatomyositis (DM) is a systemic autoimmune disorder of unknown immunopathogenesis in which the immune system targets the microvasculature of skeletal muscles, skin, and other organs. The current mainstay of therapy is a steroid regimen in combination with other immunosuppressive treatments. To date, no validated markers for monitoring disease activity have been identified, which hampers personalized treatment. This study was undertaken to identify a panel of proteins specifically related to active disease in juvenile DM. METHODS: We performed a multiplex immunoassay for plasma levels of 45 proteins related to inflammation in 25 patients with juvenile DM in 4 clinically well-defined groups, as determined by clinical activity and treatment. We compared them to 14 age-matched healthy children and 8 age-matched children with nonautoimmune muscle disease. RESULTS: Cluster analysis of circulating proteins showed distinct profiles for juvenile DM patients and controls based on a group of 10 proteins. In addition to CXCL10, tumor necrosis factor receptor type II (TNFRII) and galectin 9 were significantly increased in active juvenile DM. The levels of these 3 proteins were tightly linked to active disease and correlated with clinical scores (as measured by the Childhood Myositis Assessment Scale and physician's global assessment of disease activity on a visual analog scale). CONCLUSION: Our findings indicate that CXCL10, TNFRII, and galectin 9 correspond to disease status in juvenile DM and thus could be helpful in monitoring disease activity and guiding treatment. Furthermore, they might provide new knowledge about the pathogenesis of this autoimmune disease.