Synaptophysin-Ki67 double stain: a novel technique that improves interobserver agreement in the grading of well-differentiated gastrointestinal neuroendocrine tumors.

A common problem in the assessment of Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors is distinguishing tumor from non-tumor. This is because background stromal lymphocytes, entrapped non-neoplastic glands, and the delicate vascular network characteristic of neuroendocrine tumors frequently contain a subset of proliferating cells. Furthermore, in small biopsies, crush and cautery artifact can alter the morphologic appearance of tumor cells, making the Ki67 proliferative index more difficult to assess. To address these issues, we developed a synaptophysin-Ki67 double stain using a commercially available immunohistochemistry kit, allowing simultaneous visualization of tumor and proliferating nuclei. To test this method, three gastrointestinal pathologists individually graded 50 gastrointestinal neuroendocrine tumors first using synaptophysin-Ki67 double-stained slides and then, after a washout period, using Ki67-only stained slides (along with routine hematoxylin- and eosin-stained slides). Interobserver agreement on Ki67 proliferative index was moderate using the Ki67-only stained slides (intraclass correlation 0.51, 95% confidence interval: 0.35-0.66) and improved using the synaptophysin-Ki67 double stain (intraclass correlation 0.79, 95% confidence interval: 0.69-0.86). Similarly, interobserver agreement on tumor grade was fair with Ki67-only stained slides (κ=0.39, P<0.001) and improved with the double stain (κ=0.58, P<0.001). Analysis of individual pathologists' scores revealed that fewer total number of tumor cells counted correlated with higher grade designation and appeared to contribute to grade discordance. In tumors cited as particularly challenging to assess by the pathologists, three of four tumors were grade discordant with the Ki67-only stain, whereas all four tumors were grade concordant with the synaptophysin-Ki67 stain. The synaptophysin-Ki67 double stain is the first technique to address specifically the histomorphologic challenges of evaluating Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors. Although further validation is needed, this study provides evidence that the synaptophysin-Ki67 double stain can improve interobserver agreement

Environmental variation and geographic distribution of the Brachypodium distachyon grass complex species’ in Tunisia.

The Brachypodium genus contains the model grasses B. distachyon, B. stacei and B. hybridum, that are useful for molecular and physiological studies relevant to grain, pasture and bioenergy crops, as well as ecology. In this paper, we analyze the natural variation in climate/geographical diversity that exists within these species in the Tunisian territory. To capture the genetic diversity within this species complex in relation to their geographic distribution in Tunisia, 360 of Brachypodium accessions from the Tunisian territory were collected and genotyped by ALB165 marker. Overall, 314 samples were classified into hybridum and the rest as diploid for one of the two progenitor’s species (B. distachyon and B. stacei). Environmental niche analysis indicated that, generally, B. distachyon grows in higher, cooler, and wetter places north of 36°; B. stacei in lower, warmer, and drier places; nd B. hybridum in places with intermediate ecological features and across latitudinal boundaries but also overlapping with those of its parents, more often with those of B. stacei

Reseña bibliográfica. la economía colombiana en la década de los setenta

Los cinco ensayos que conforman este libro fueron escritos bajo diferentes motivaciones y en coyunturas diversas, con un nivel de profundidad irregular, sin buscar ni lograr construir una reflexión unitaria sobre la economía colombiana del decenio pasado. La cubierta hace aún más desafortunada la presentación del libro. A su diseñador, lo más arriesgado e innovador que se le ocurre es resaltar lo alusivo a la economía colombiana, apoyándose en el gastado recurso tricolor del númerosetenta que forma parte del título. Para hacer justicia a lo anotado sobre lo no unitario del texto, éste debe ser analizado en cada una de sus partes

Language experience enhances early cortical pitch-dependent responses

AbstractPitch processing at cortical and subcortical stages of processing is shaped by language experience. We recently demonstrated that specific components of the cortical pitch response (CPR) index the more rapidly-changing portions of the high rising Tone 2 of Mandarin Chinese, in addition to marking pitch onset and sound offset. In this study, we examine how language experience (Mandarin vs. English) shapes the processing of different temporal attributes of pitch reflected in the CPR components using stimuli representative of within-category variants of Tone 2. Results showed that the magnitude of CPR components (Na–Pb and Pb–Nb) and the correlation between these two components and pitch acceleration were stronger for the Chinese listeners compared to English listeners for stimuli that fell within the range of Tone 2 citation forms. Discriminant function analysis revealed that the Na–Pb component was more than twice as important as Pb–Nb in grouping listeners by language affiliation. In addition, a stronger stimulus-dependent, rightward asymmetry was observed for the Chinese group at the temporal, but not frontal, electrode sites. This finding may reflect selective recruitment of experience-dependent, pitch-specific mechanisms in right auditory cortex to extract more complex, time-varying pitch patterns. Taken together, these findings suggest that long-term language experience shapes early sensory level processing of pitch in the auditory cortex, and that the sensitivity of the CPR may vary depending on the relative linguistic importance of specific temporal attributes of dynamic pitch

(R)-(3-Carb­oxy-2-hy­droxy­prop­yl)tri­methyl­aza­nium chloride

In the title salt (common name l-carnitine hydro­chloride), C7H16NO3 +·Cl−, the organic cation features a carb­oxy­lic part (–CO2H) having unambigous single- and double-bonds [1.336 (2), 1.211 (2) Å]. There is a large N—C—C bond angle [115.9 (1)°] for the C atom connected to the bulky trimethyl­amino substituent. In the crystal, the acid H atom forms a hydrogen bond to the chloride anion, whereas the hydroxyl H atom forms a longer hydrogen bond to the anion, generating a helical chain running along [001]