Does somatostatin or gastric inhibitory peptide receptor expression correlate with tumor grade and stage in gut neuroendocrine tumors?

BACKGROUND/AIMS Important characteristics of neuroendocrine neoplasms (NEN) for prognosis and therapeutic decisions are the MIB-1 proliferative index (tumor grade) and tumor stage. Moreover, these tumors express peptide hormone receptors like somatostatin and gastric inhibitory peptide (GIP) receptors which represent important established and potential future targets, respectively, for molecular imaging and radiotherapy. However, the interrelation between tumor proliferation, stage, and peptide receptor amounts has never been assessed. METHODS In 114 gastrointestinal and bronchopulmonary NEN, the proliferative rate assessed with MIB-1 immunohistochemistry and tumor stage were compared with the somatostatin type 2 receptor (sst2) and GIP receptor expression measured quantitatively with in vitro receptor autoradiography. RESULTS NEN generally showed high sst2 and GIP receptor expression. GIP receptor but not sst2 expression correlated with the MIB-1 index. GIP receptor levels gradually increased in a subset of insulinomas and nonfunctioning pancreatic NEN, and decreased in ileal and bronchopulmonary NEN with increasing MIB-1 rate. MIB-1 levels were identified, above which GIP receptor levels were consistently high or low. These MIB-1 levels were clearly different from those defining tumor grade. In grade 3 NEN, GIP receptor levels were always low, while sst2 levels were variable and sometimes extremely high. Conversely, sst2 expression correlated more frequently with tumor stage than GIP receptor expression, with metastasized NEN showing higher sst2 levels than localized tumors. CONCLUSIONS sst2, a clinically crucial molecular target, shows variable and unpredictable expression in NEN irrespective of tumor grade. Therefore, each NEN should be tested for sst2 if clinical applications with somatostatin analogs are considered. Conversely, the potential future role of GIP receptors as molecular targets in NEN may be dependent on the MIB-1 level.

P-T-t estimation of syn-kinematic strain in low-grade quartz-feldspar bearing rocks using thermodynamic modeling and 40Ar/39Ar dating techniques: example of the Plan-de-Phasy shear zone unit (Briançonnais Zone, Western Alps)

Pressure–Temperature–time (P–T–t) estimates of the syn-kinematic strain at the peak-pressure conditions reached during shallow underthrusting of the Briançonnais Zone in the Alpine subduction zone was made by thermodynamic modelling and 40Ar/39Ar dating in the Plan-de-Phasy unit (SE of the Pelvoux Massif, Western Alps). The dated phengite minerals crystallized syn-kinematically in a shear zone indicating top-to-the-N motion. By combining X-ray mapping with multi-equilibrium calculations, we estimate the phengite crystallization conditions at 270 ± 50 °C and 8.1 ± 2 kbar at an age of 45.9 ± 1.1 Ma. Combining this P–T–t estimate with data from the literature allows us to constrain the timing and geometry of Alpine continental subduction. We propose that the Briançonnais units were scalped on top of the slab during ongoing continental subduction and exhumed continuously until collision.

Multi-grade teaching practices in Austrian and Finnish primary schools

This article describes the teaching strategies used in multi-grade classes in five small rural primary schools in Austria and Finland on the basis of the content analysis of transcribed teacher interviews. Two main types of strategies were identified: practices that (1) aim to reduce or (2) capitalize on students’ heterogeneity. The results illustrate how differently multi-grade teaching can be realized and how it can effectively support individual student learning. The findings are discussed with regard to teacher education with the intention of increasing the awareness of the professional skills required in high-quality teaching practices in multi-grade teaching.

Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study.

BACKGROUND Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. METHODS In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 - 8.5). RESULTS Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-α (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1β and IL-6 did not significantly differ between the two groups. CONCLUSIONS Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies.

Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.

BACKGROUND Knowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly. AIM To evaluate the impact of symptom severity, endoscopic and histological activity on EoE-specific QoL in adult EoE patients. METHODS Ninety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL. RESULTS Quality of life strongly correlated with symptom severity (r = 0.610, P < 0.001). While the variation in severity of symptoms, endoscopic and histological findings alone explained 38%, 35% and 22% of the variability in EoE-related QoL, respectively, these together explained 60% of variation. Symptom severity explained 18-35% of the variation in each of the five QoL subscale scores. CONCLUSIONS Eosinophilic oesophagitis symptom severity and biological disease activity determine QoL in adult patients with eosinophilic oesophagitis. Therefore, reduction in both eosinophilic oesophagitis symptoms as well as biological disease activity is essential for improvement of QoL in adult patients. Clinicaltrials.gov number, NCT00939263.

The Quality of the Evidence According to GRADE Is Predominantly Low or Very Low in Oral Health Systematic Reviews

OBJECTIVES The main objective was to assess the credibility of the evidence using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) in oral health systematic reviews on the Cochrane Database of Systematic Reviews (CDSR) and elsewhere. STUDY DESIGN AND SETTING Systematic Reviews or meta-analyses (January 2008-December 2013) from 14 high impact general dental and specialty dental journals and the Cochrane Database of Systematic Reviews were screened for meta-analyses. Data was collected at the systematic review, meta-analysis and trial level. Two reviewers applied and agreed on the GRADE rating for the selected meta-analyses. RESULTS From the 510 systematic reviews initially identified 91 reviews (41 Cochrane and 50 non-Cochrane) were eligible for inclusion. The quality of evidence was high in 2% and moderate in 18% of the included meta-analyses with no difference between Cochrane and non-Cochrane reviews, journal impact factor or year of publication. The most common domains prompting downgrading of the evidence were study limitations (risk of bias) and imprecision (risk of play of chance). CONCLUSION The quality of the evidence in oral health assessed using GRADE is predominantly low or very low suggesting a pressing need for more randomised clinical trials and other studies of higher quality in order to inform clinical decisions thereby reducing the risk of instituting potentially ineffective and/or harmful therapies.

Small-diameter titanium grade IV and titanium-zirconium implants in edentulous mandibles: five-year results from a double-blind, randomized controlled trial.

BACKGROUND The aim of this study was to compare the 5-year survival and success rates of 3.3 mm dental implants either made from titanium-zirconium (TiZr) alloy or from Grade IV titanium (Ti Grade IV) in mandibular implant-based removable overdentures. METHODS The core study had a follow-up period of 36 months and was designed as a randomized, controlled, double-blind, split-mouth multicenter clinical trial. Patients with edentulous mandibles received two Straumann Bone Level implants (diameter 3.3 mm, SLActive®), one of TiZr (test) and one of Ti Grade IV (control), in the interforaminal region. This follow-up study recruited patients from the core study and evaluated the plaque and sulcus bleeding indices, radiographic crestal bone level, as well as implant survival and success 60 months after implant placement. RESULTS Of the 91 patients who initially received implants, 75 completed the 36 month follow-up and 49 were available for the 60 month examination. Two patients were excluded so that a total of 47 patients with an average age of 72 ± 8 years were analysed. The characteristics and 36-month performance of the present study cohort did not differ from the non-included initial participants (p > 0.05). In the period since the 36-month follow-up examination, no implant was lost. The cumulative implant survival rate was 98.9 % for the TiZr group and 97.8 % for the Ti Grade IV group. Crestal bone level changes at 60 months were not different in the test and control group (TiZr -0.60 ± 0.69 mm and Ti Grade IV -0.61 ± 0.83 mm; p = 0.96). The cumulative implant success rate after 60 months was 95.8 and 92.6 % for TiZr and Ti Grade IV, respectively. CONCLUSIONS After 60 months, the positive outcomes of the 36 month results for TiZr and Ti Grade IV implants were confirmed, with no significant differences with regard to crestal bone level change, clinical parameters and survival or success rates. TiZr implants performed equally well compared to conventional Ti Grade IV 3.3 mm diameter-reduced implants for mandibular removable overdentures. TRIAL REGISTRATION Registered on www.clinicaltrials.gov: NCT01878331.

Small-diameter titanium Grade IV and titanium-zirconium implants in edentulous mandibles: three-year results from a double-blind, randomized controlled trial

OBJECTIVE The aim of this study was to compare crestal bone-level changes, soft tissue parameters and implant success and survival between small-diameter implants made of titanium/zirconium (TiZr) alloy or of Grade IV titanium (Ti) in edentulous mandibles restored with removable overdentures. MATERIALS AND METHODS This was a randomized, controlled, double-blind, split-mouth multicenter clinical trial. Patients with edentulous mandibles received two Straumann bone-level implants (diameter 3.3 mm), one of Ti Grade IV (control) and one of TiZr (test), in the interforaminal region. Implants were loaded after 6-8 weeks and removable Locator-retained overdentures were placed within 2 weeks of loading. Modified plaque and sulcus bleeding indices, radiographic bone level, and implant survival and success were evaluated up to 36 months. RESULTS Of 91 treated patients, 75 completed the three-year follow-up. Three implants were lost (two control and one test implant). The survival rates were 98.7% and 97.3%, and the mean marginal bone level change was -0.78 ± 0.75 and -0.60 ± 0.71 mm for TiZr and Ti Grade IV implants. Most patients had a plaque score of 0 or 1 (54% for test and 51.7% for control), and a sulcus bleeding score of 0 (46.1% for test and 44.9% for control). No significant differences were found between the two implant types for bone-level change, soft tissue parameters, survival and success. CONCLUSIONS After 36 months, similar outcomes were found between Ti Grade IV and TiZr implants. The results confirm that the results seen at 12 months continue over time.

The Effect of Broadleaf Canopies on Survey-grade Horizontal GPS/GLONASS Measurements

A study was conducted to empirically determine the degradation of survey-grade GPS horizontal position measurements due to the effects of broadleaf forest canopies. The measurements were taken using GPS/GLONASS-capable receivers measuring C/A and P-codes, and carrier phase. Fourteen survey markers were chosen in central Connecticut to serve as reference markers for the study. These markers had varying degrees of sky obstruction due to overhanging tree canopies. Sky obstruction was measured by photographing the sky with a 35mm reflex camera fitted with a hemispherical lens. The negative was scanned and the image mapped using an equal- area projection to remove the distortion caused by the lens. The resulting digital image was thresholded to produce a black-and-white image in which a count of the black pixels is a measure of sky-area obstruction. The locations of the markers were determined independently before the study. During the study, each marker was occupied for four 20-minute sessions over the period of one week in mid-July, 1999. The location of the study markers produced relatively long baselines, as compared with similar studies. We compared the accuracy of GPS-only vs. GPS&GLONASS as a function of sky obstruction. Based on our results, GLONASS observations did not improve or degrade the accuracy of the position measurements. There is a loss of 2mm of accuracy per percent of sky obstruction for both GPS only and GPS&GLONASS.

The Effect of Direct Instruction versus Discovery Learning on the Understanding of Science Lessons by Second Grade Students

This study examined the effectiveness of discovery learning and direct instruction in a diverse second grade classroom. An assessment test and transfer task were given to students to examine which method of instruction enabled the students to grasp the content of a science lesson to a greater extent. Results demonstrated that students in the direct instruction group scored higher on the assessment test and completed the transfer task at a faster pace; however, this was not statistically significant. Results also suggest that a mixture of instructional styles would serve to effectively disseminate information, as well as motivate students to learn.

The Relationship of Student Demographics to 10th Grade MCAS Test Anxiety

The intensification of consequential testing situations is associated with an increase in anxiety among American students (Casbarro, 2005). Test anxiety can have negative effects on student test performance (Everson, Millsap, & Rodriguez, 1991). If test anxiety has the potential to decrease students’ test scores, it becomes a factor that can threaten the validity of any inferences drawn between test scores and student progress (Cizek & Burg, 2006). There are several factors that relate closely to test anxiety (Cizek & Burg, 2006). Variables of key influence include gender, socioeconomic status, and teacher-manifested anxiety (Hembree, 1988). Another influence upon test anxiety is students’ participation in academic support programs to prepare them for exit examinations. The purpose of this study was to examine the relationship between 10th grade high school student gender, socioeconomic status, perceived teacher anxiety, and student preparedness with levels of the Massachusetts Comprehensive Assessment System (MCAS) test anxiety. It appears that few studies have examined levels of high school test anxiety in regards to this specific high-stakes MCAS exit exam required for high school graduation. A two-phase sequential mixed-methods research design was used to survey (N=156) 10th grade students represented by a sampling of (n=80) students with low socioeconomic status and (n=76) students with high socioeconomic status regarding their levels of test anxiety in relation to upcoming MCAS testing. A multiple regression analysis was used to measure the relationship between the predictor variables (gender, socioeconomic status, perceived teacher anxiety, and student preparedness) with the criterion variable of student test anxiety using the Test Anxiety Inventory (TAI). Personal interviews with (n=20) volunteer students provided rich explanations of students’ academic self-efficacy, their perceptions of their performance on the upcoming MCAS exam, and their use of strategies to reduce their levels of test anxiety. Personal interviews with (n=12) volunteer school administrators and teachers provided descriptions of their perceptions of how test anxiety affected their students’ performance. A major quantitative finding of this study was that the variables of student socioeconomic status and student ratings of teacher anxiety accounted for the variance in students’ levels of surveyed test anxiety (R2 = .06, p = .033, small to medium effect size). These results indicate that different student populations vary in their readiness skills to successfully participate in consequential testing situations. Consequently, high-test anxious students would require emotional preparation as well as academic preparation when confronting high-stakes testing. The results have the potential to re-shape the format of schools’ MCAS test preparation efforts.