A study of the endocervical columnar cells I - morphology and frequency

After the observation of many thousands of histological sections of the endocervical mucosa it became evident that its columnar cells present a great variety of aspects not only those of the surface of the canal but also those of the glands. A classification of these cells was made taking into account the staining affinity, the intensity staining of the cytoplasm, the presence or absence of cilia, the shape and location of the nucleus. The various combinations of these different data made possible the characterization of 26 types of cells which we labelled by the alphabetical letters. Two hundred and fifty cervices obtained by cervical amputation and by hysterectomy were studied. The uteri presented lesions in the course of routine laboratory examination. In each of the 250 histological sections there were specifically counted 2,000 columnar cells which cover the cervical canal and 2,000columnar cells which form the glands. A graphic representation of the frequency of both the superficial and glandular columnar cells was presented; this was given the name EPITHELIOGRAM. The variation of the cellular "composition" of each epithelium is discussed and the frequency of the various cellular types after the count of one million of cells is presented.

Determinació de la ubicació estructural dels ions Yb3+ i Nb3+ en Yb:RTP, Nb:RTP i (Nb,Yb):RTP

Estudi elaborat a partir d’una estada al Stony Brook University al juliol del 2006. El RbTiOPO4 (RTP) monocristal•lí és un material d' òptica no lineal molt rellevant i utilitzat en la tecnologia làser actual, químicament molt estable i amb unes propietats físiques molt destacades, entre elles destaquen els alts coeficients electro-òptics i l'alt llindar de dany òptic que presenta. En els últims anys s’està utilitzant tecnològicament en aplicacions d'òptica no lineal en general i electro-òptiques en particular. En alguns casos ja ha substituït, millorant prestacions, a materials tals com el KTP o el LNB(1). Dopant RTP amb ions lantànids (Ln3+) (2-4), el material es converteix en un material làser auto-doblador de freqüència, combinant les seves propietats no lineals amb les de matriu làser. El RTP genera radiació de segon harmònic (SHG) a partir d’un feix fonamental amb longituds d’ona inferiors a 990 nm, que és el límit que presenta el KTP.La determinació de la ubicació estructural i l’estudi de l'entorn local del ions actius làser és de fonamental importància per a la correcta interpretació de les propietats espectroscòpiques d’aquest material. Mesures de difracció de neutrons sobre mostra de pols cristal•lí mostren que els ions Nb5+ i Ln3+ només substitueixin posicions de Ti4+ (8-9). Estudis molt recents d'EPR (electron paramagnetic resonance) semblen indicar que quan la concentració d'ió Ln3+ es baixa, aquest ió presenta la tendència a substituir l'ió alcalí present a l'estructura (10).Després dels resultats obtinguts en el present treball a partir de la tècnica EXAFS a la instal•lació sincrotò del Brookhaven National Laboratory/State University of New York (Stony Brook) es pot concloure definitivament que els ions Nb s’ubiquen en la posició Ti (1) i que els ions Yb3+ es distribueixen paritariament en les dues posicions del Ti (1 i 2). Aquests resultats aporten una valuosa informació per a la correcta interpretació dels espectres, tant d’absorció com d’emissió, del material i per la avaluació dels paràmetres del seu comportament durant l'acció làser.

High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets.

OBJECTIVE-We studied whether manganese-enhanced high-field magnetic resonance (MR) imaging (MEHFMRI) could quantitatively detect individual islets in situ and in vivo and evaluate changes in a model of experimental diabetes.RESEARCH DESIGN AND METHODS-Whole pancreata from untreated (n = 3), MnCl(2) and glucose-injected mice (n = 6), and mice injected with either streptozotocin (STZ; n = 4) or citrate buffer (n = 4) were imaged ex vivo for unambiguous evaluation of islets. Exteriorized pancreata of MnCl(2) and glucose-injected mice (n = 6) were imaged in vivo to directly visualize the gland and minimize movements. In all cases, MR images were acquired in a 14.1 Testa scanner and correlated with the corresponding (immuno)histological sections.RESULTS-In ex vivo experiments, MEHFMRI distinguished different pancreatic tissues and evaluated the relative abundance of islets in the pancreata of normoglycemic mice. MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice. However, in the latter measurements the loss of beta-cells was undervalued under the conditions tested. The experiments on the externalized pancreata confirmed that MEHFMRI could visualize native individual islets in living, anesthetized mice.CONCLUSIONS-Data show that MEHFMRI quantitatively visualizes individual islets in the intact mouse pancreas, both ex vivo and in vivo. Diabetes 60:2853-2860, 2011

Properties of functional brain networks correlate with frequency of psychogenic non-epileptic seizures.

Abnormalities in the topology of brain networks may be an important feature and etiological factor for psychogenic non-epileptic seizures (PNES). To explore this possibility, we applied a graph theoretical approach to functional networks based on resting state EEGs from 13 PNES patients and 13 age- and gender-matched controls. The networks were extracted from Laplacian-transformed time-series by a cross-correlation method. PNES patients showed close to normal local and global connectivity and small-world structure, estimated with clustering coefficient, modularity, global efficiency, and small-worldness (SW) metrics, respectively. Yet the number of PNES attacks per month correlated with a weakness of local connectedness and a skewed balance between local and global connectedness quantified with SW, all in EEG alpha band. In beta band, patients demonstrated above-normal resiliency, measured with assortativity coefficient, which also correlated with the frequency of PNES attacks. This interictal EEG phenotype may help improve differentiation between PNES and epilepsy. The results also suggest that local connectivity could be a target for therapeutic interventions in PNES. Selective modulation (strengthening) of local connectivity might improve the skewed balance between local and global connectivity and so prevent PNES events.

Reproducibility of free-breathing cardiovascular magnetic resonance coronary angiography.

OBJECTIVE: Contemporary free-breathing non contrast enhanced cardiovascular magnetic resonance angiography (CMRA) was qualitatively and quantitatively evaluated to ascertain the reproducibility of the method for coronary artery luminal dimension measurements. SUBJECTS AND METHODS: Twenty-two healthy volunteers (mean age 32 +/- 7 years, 12 males) without coronary artery disease were imaged at 2 centers (1 each in Europe and North America) using navigator-gated and corrected SSFP CMRA on a commercial whole body 1.5T System. Repeat images of right (RCA, n = 21), left anterior descending (LAD, n = 14) and left circumflex (LCX, n = 14) coronary arteries were obtained in separate sessions using identical scan protocol and imaging parameters. True visible vessel length, signal-to-noise (SNR), contrast-to-noise ratios (CNR) and the average luminal diameter over the first 4 cm of the vessel were measured. Intra-observer, inter-observer and inter-scan reproducibility of coronary artery luminal diameter were determined using Pearson's correlation, Bland-Altman analysis and intraclass correlation coefficients (ICC). RESULTS: CNR, SNR and the mean length of the RCA, LAD and LCX imaged for original and repeat scans were not significantly different (all p > 0.30). There was a high degree of intra-observer, inter-observer and inter-scan agreements for RCA, LAD and LCX luminal diameter respectively on Bland-Altman and ICC analysis (ICC's for RCA: 0.98. 0.98 and 0.86; LAD: 0.89, 0.89 and 0.63; LCX: 0.95, 0.94 and 0.79). CONCLUSION: In a 2-center study, we demonstrate that free-breathing 3D SSFP CMRA can visualize long continuous segments of coronary vessels with highly reproducible measurements of luminal diameter.

Quantification of aortic flow by phase-contrast magnetic resonance in patients with bicuspid aortic valve.

AIMS: Bicuspid aortic valve (BAV) causes complex flow patterns in the ascending aorta (AAo), which may compromise the accuracy of flow measurement by phase-contrast magnetic resonance (PC-MR). Therefore, we aimed to assess and compare the accuracy of forward flow measurement in the AAo, where complex flow is more dominant in BAV patients, with flow quantification in the left ventricular outflow tract (LVOT) and the aortic valve orifice (AV), where complex flow is less important, in BAV patients and controls. METHODS AND RESULTS: Flow was measured by PC-MR in 22 BAV patients and 20 controls at the following positions: (i) LVOT, (ii) AV, and (iii) AAo, and compared with the left ventricular stroke volume (LVSV). The correlation between the LVSV and the forward flow in the LVOT, the AV, and the AAo was good in BAV patients (r = 0.97/0.96/0.93; P < 0.01) and controls (r = 0.96/0.93/0.93; P < 0.01). However, in relation with the LVSV, the forward flow in the AAo was mildly underestimated in controls and much more in BAV patients [median (inter-quartile range): 9% (4%/15%) vs. 22% (8%/30%); P < 0.01]. This was not the case in the LVOT and the AV. The severity of flow underestimation in the AAo was associated with flow eccentricity. CONCLUSION: Flow measurement in the AAo leads to an underestimation of the forward flow in BAV patients. Measurement in the LVOT or the AV, where complex flow is less prominent, is an alternative means for quantifying the systolic forward flow in BAV patients.

Evaluation of the reconstruction limits of a frequency-independent crosshole georadar waveform inversion scheme in the presence of dispersion

Waveform tomographic imaging of crosshole georadar data is a powerful method to investigate the shallow subsurface because of its ability to provide images of pertinent petrophysical parameters with extremely high spatial resolution. All current crosshole georadar waveform inversion strategies are based on the assumption of frequency-independent electromagnetic constitutive parameters. However, in reality, these parameters are known to be frequency-dependent and complex and thus recorded georadar data may show significant dispersive behavior. In this paper, we evaluate synthetically the reconstruction limits of a recently published crosshole georadar waveform inversion scheme in the presence of varying degrees of dielectric dispersion. Our results indicate that, when combined with a source wavelet estimation procedure that provides a means of partially accounting for the frequency-dependent effects through an "effective" wavelet, the inversion algorithm performs remarkably well in weakly to moderately dispersive environments and has the ability to provide adequate tomographic reconstructions.

The demand for intensity versus frequency of alcohol consumption: Evidence from rural Australia

This paper develops a theoretical model for the demand of alcohol where intensity and frequency of consumption are separate choices made by individuals in order to maximize their utility. While distinguishing between intensity and frequency of consumption may be unimportant for many goods, this is clearly not the case with alcohol where the likelihood of harm depends not only on the total consumed but also on the pattern of use. The results from the theoretical model are applied to data from rural Australia in order to investigate the factors that affect the patterns of alcohol use for this population group. This research can play an important role in informing policies by identifying those factors which influence preferences for patterns of risky alcohol use and those groups and communities who are most at risk of harm.

Which prior knowledge? Quantification of in vivo brain 13C MR spectra following 13C glucose infusion using AMARES.

The recent developments in high magnetic field 13C magnetic resonance spectroscopy with improved localization and shimming techniques have led to important gains in sensitivity and spectral resolution of 13C in vivo spectra in the rodent brain, enabling the separation of several 13C isotopomers of glutamate and glutamine. In this context, the assumptions used in spectral quantification might have a significant impact on the determination of the 13C concentrations and the related metabolic fluxes. In this study, the time domain spectral quantification algorithm AMARES (advanced method for accurate, robust and efficient spectral fitting) was applied to 13 C magnetic resonance spectroscopy spectra acquired in the rat brain at 9.4 T, following infusion of [1,6-(13)C2 ] glucose. Using both Monte Carlo simulations and in vivo data, the goal of this work was: (1) to validate the quantification of in vivo 13C isotopomers using AMARES; (2) to assess the impact of the prior knowledge on the quantification of in vivo 13C isotopomers using AMARES; (3) to compare AMARES and LCModel (linear combination of model spectra) for the quantification of in vivo 13C spectra. AMARES led to accurate and reliable 13C spectral quantification similar to those obtained using LCModel, when the frequency shifts, J-coupling constants and phase patterns of the different 13C isotopomers were included as prior knowledge in the analysis.

Coronary magnetic resonance angiography for assessment of the stent lumen: a phantom study.

PURPOSE: To evaluate the feasibility of visualizing the stent lumen using coronary magnetic resonance angiography in vitro. MATERIAL AND METHODS: Nineteen different coronary stents were implanted in plastic tubes with an inner diameter of 3 mm. The tubes were positioned in a plastic container filled with gel and included in a closed flow circuit (constant flow 18 cm/sec). The magnetic resonance images were obtained with a dual inversion fast spin-echo sequence. For intraluminal stent imaging, subtraction images were calculated from scans with and without flow. Subsequently, intraluminal signal properties were objectively assessed and compared. RESULTS: As a function of the stent type, various degrees of in-stent signal attenuation were observed. Tantalum stents demonstrated minimal intraluminal signal attenuation. For nitinol stents, the stent lumen could be identified, but the intraluminal signal was markedly reduced. Steel stents resulted in the most pronounced intraluminal signal voids. CONCLUSIONS: With the present technique, radiofrequency penetration into the stents is strongly influenced by the stent material. Thesefindings may have important implicationsforfuture stent design and stent imaging strategies.

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

OBJECTIVES: It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS: This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS: Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS: Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency.

Microsatellite instability (MSI) occurs in 10-20% of colorectal tumours and is associated with good prognosis. Here we describe the development and validation of a genomic signature that identifies colorectal cancer patients with MSI caused by DNA mismatch repair deficiency with high accuracy. Microsatellite status for 276 stage II and III colorectal tumours has been determined. Full-genome expression data was used to identify genes that correlate with MSI status. A subset of these samples (n = 73) had sequencing data for 615 genes available. An MSI gene signature of 64 genes was developed and validated in two independent validation sets: the first consisting of frozen samples from 132 stage II patients; and the second consisting of FFPE samples from the PETACC-3 trial (n = 625). The 64-gene MSI signature identified MSI patients in the first validation set with a sensitivity of 90.3% and an overall accuracy of 84.8%, with an AUC of 0.942 (95% CI, 0.888-0.975). In the second validation, the signature also showed excellent performance, with a sensitivity 94.3% and an overall accuracy of 90.6%, with an AUC of 0.965 (95% CI, 0.943-0.988). Besides correct identification of MSI patients, the gene signature identified a group of MSI-like patients that were MSS by standard assessment but MSI by signature assessment. The MSI-signature could be linked to a deficient MMR phenotype, as both MSI and MSI-like patients showed a high mutation frequency (8.2% and 6.4% of 615 genes assayed, respectively) as compared to patients classified as MSS (1.6% mutation frequency). The MSI signature showed prognostic power in stage II patients (n = 215) with a hazard ratio of 0.252 (p = 0.0145). Patients with an MSI-like phenotype had also an improved survival when compared to MSS patients. The MSI signature was translated to a diagnostic microarray and technically and clinically validated in FFPE and frozen samples.