Weak self-directed learning skills hamper performance in cumulative assessment

Background: Self-regulated learning is an important determinant of academic performance. Previous research has shown that cumulative assessment encourages students to work harder and improve their results. However, not all students seem to respond as intended. We investigated the influence of students’ behavioral traits on their responsiveness to a cumulative assessment strategy.

Method: The cumulative test results of a third-year integrated ten-week course unit were analyzed. The test was divided into three parts delivered at 4, 8 and 10 weeks. Low starters (below median) with low or high improvement (below or above the median) were identified and compared regarding their behavioral traits (assessed with the Temperament and Character Inventory questionnaire).

Results: A total of 295 students filled out the questionnaire. A percentage of 70% of the students below the median on the first two test parts improved during the final part. Students who were less responsive to improve their test results, scored low only on the TCI scale “self directedness” (t?=?2.49; p?=?0.011).

Conclusion: Behavioral traits appear to influence student reactions to feedback on test results, with students with low self-directedness scores being particularly at risk. They can thus be identified and should receive special attention from student counselors.     

Venous Thromboembolic Events Following Major Pelvic and Abdominal Surgeries for Cancer: A Prospective Cohort Study

Objective

The aim of this study was to evaluate the incidence and risk factors for post-hospital discharge venous thromboembolism (VTE) following abdominal cancer surgery without post-discharge prophylaxis.

Methods

This was a single-center, prospective cohort study. Patients were evaluated at 1, 3, and 6 months from surgery for the presence of proximal deep vein thrombosis (DVT; screening ultrasound at 1 month and questionnaire at each visit). Cumulative VTE incidence with 95% confidence interval (CI) was estimated using Kaplan–Meier methods, and multivariable analysis was performed using a Cox proportional hazards model.

Results

Of 284 patients enrolled, 79 (28%) underwent colorectal laparotomy, 97 (34%) underwent hepatobiliary laparotomy, 100 (35%) underwent gynecological laparotomy, and 8 (3%) underwent exploratory laparotomy without resection. All patients received pre- and postoperative inpatient prophylaxis. The cumulative incidence of VTE at 1 month was 0.35% (95% CI 0.05–2.48), 2.5% at 3 months (95% CI 1.19–5.15), and 7.2% at 6 months (95% CI 4.72–10.97). Screening ultrasound performed 4 weeks after surgery in 50% of patients was negative for thrombosis in all cases. Event distribution was similar according to the type of surgery (open/laparoscopic) and type of cancer. Seventeen (6.6%) patients died (95% CI 3.5–9.4) (two had a VTE-related death). Postoperative chemotherapy and Caprini score were significantly associated with VTE [hazard ratios 3.77 (95% CI 1.56–9.12) and 1.17 (95% CI 1.02–1.34), respectively].

Conclusion

The incidence of post-hospital discharge proximal DVT and/or symptomatic VTE following abdominal and pelvic cancer surgery appears to be low. The cumulative number of events increased at 6 months, but this was likely due to additional risk factors that were not related to surgery. Postoperative chemotherapy increases the risk of VTE.

     

Identification of unknown impurities in simvastatin substance and tablets by liquid chromatography/tandem mass spectrometry

Unknown impurities were detected in simvastatin substance and tablets at a 0.2% level using the liquid chromatography technique with UV (DAD) detection. The impurity structures were elucidated by a direct hyphenation of liquid chromatograph to high-resolution mass spectrometer with electrospray ionisation interface using solutions of formic acid in water and in acetonitrile as the mobile phase. Peak tracking was performed using the column-switching technique. Accurate mass measurements by quadrupole time-of-flight mass spectrometer equipped with lock-spray provided information about elemental composition of intact molecules and fragments of impurities. Measurement accuracy for precursor ions was around 3 ppm and for fragment ions between 4 and 13 ppm. Mass resolving power was around 6500. Deduced molecular formulae for A1, A2 and A3 impurities were C(27)H(44)O(6), C(26)H(43)O(6) and C(26)H(41)O(5), respectively. The structures proposed for all three impurities revealed modifications of simvastatin molecule on the lactone ring. Impurity A1, detected in simvastatin tablets, was identified as ethyl ester, while the impurities A2 and A3, detected in simvastatin substance, were identified as methyl ester and methyl ether of simvastatin. The impurity from tablets was synthesized and its structure confirmed by LC-UV, LC-MS/MS, and NMR techniques.     

Murine Recombinant Angiotensin-Converting Enzyme 2: Effect on Angiotensin II-Dependent Hypertension and Distinctive Angiotensin-Converting Enzyme 2 Inhibitor Characteristics on Rodent and Human Angiotensin-Converting Enzyme 2

A newly produced murine recombinant angiotensin (Ang)-converting enzyme 2 (ACE2) was characterized in vivo and in vitro. The effects of available ACE2 inhibitors (MLN-4760 and 2 conformational variants of DX600, linear and cyclic) were also examined. When murine ACE2 was given to mice for 4 weeks, a marked increase in serum ACE2 activity was sustainable. In acute studies, mouse ACE2 (1 mg/kg) obliterated hypertension induced by Ang II infusion by rapidly decreasing plasma Ang II. These effects were blocked by MLN-4760 but not by either form of DX600. In vitro, conversion from Ang II to Ang-(1-7) by mouse ACE2 was blocked by MLN-4760 (10(-6) m) but not by either form of DX600 (10(-5) m). Quantitative analysis of multiple Ang peptides in plasma ex vivo revealed formation of Ang-(1-9) from Ang I by human but not by mouse ACE2. Both human and mouse ACE2 led to the dissipation of Ang II with formation of Ang (1-7). By contrast, mouse ACE2-driven Ang-(1-7) formation from Ang II was blocked by MLN-4760 but not by either linear or cyclic DX600. In conclusion, sustained elevations in serum ACE2 activity can be accomplished with murine ACE2 administration, thereby providing a strategy for ACE2 amplification in chronic studies using rodent models of hypertension and cardiovascular disease. Human but not mouse ACE2 degrades Ang I to form Ang-(1-9). There are also species differences regarding rodent and human ACE2 inhibition by known inhibitors such that MLN-4760 inhibits both human and mouse ACE2, whereas DX600 only blocks human ACE2 activity.     

Inhibitors of Leishmania mexicana CRK3 cyclin-dependent kinase: chemical library screen and antileishmanial activity

The CRK3 cyclin-dependent kinase of Leishmania has been shown by genetic manipulation of the parasite to be essential for proliferation. We present data which demonstrate that chemical inhibition of CRK3 impairs the parasite's viability within macrophages, thus further validating CRK3 as a potential drug target. A microtiter plate-based histone H1 kinase assay was developed to screen CRK3 against a chemical library enriched for protein kinase inhibitors. Twenty-seven potent CRK3 inhibitors were discovered and screened against Leishmania donovani amastigotes in vitro. Sixteen of the CRK3 inhibitors displayed antileishmanial activity, with a 50% effective dose (ED50) of less than 10 microM. These compounds fell into four chemical classes: the 2,6,9-trisubstituted purines, including the C-2-alkynylated purines; the indirubins; the paullones; and derivatives of the nonspecific kinase inhibitor staurosporine. The paullones and staurosporine derivatives were toxic to macrophages. The 2,6,9-trisubstituted purines inhibited CRK3 in vitro, with 50% inhibitory concentrations ranging from high nanomolar to low micromolar concentrations. The most potent inhibitors of CRK3 (compounds 98/516 and 97/344) belonged to the indirubin class; the 50% inhibitory concentrations for these inhibitors were 16 and 47 nM, respectively, and the ED50s for these inhibitors were 5.8 and 7.6 microM, respectively. In culture, the indirubins caused growth arrest, a change in DNA content, and aberrant cell types, all consistent with the intracellular inhibition of a cyclin-dependent kinase and disruption of cell cycle control. Thus, use of chemical inhibitors supports genetic studies to confirm CRK3 as a validated drug target in Leishmania and provides pharmacophores for further drug development.     

Color Doppler ultrasonography is reliable in assessing the risk of esophageal variceal bleeding in patients with liver cirrhosis

PURPOSE: The aim of the study was to examine the role of Doppler ultrasonography of the portal vein in predicting esophageal variceal bleeding in patients with liver cirrhosis and portal hypertension by comparing the ultrasound data to the endoscopic findings. PATIENTS AND METHODS: 99 patients with liver cirrhosis and esophageal varices underwent color Doppler ultrasonography and esophagogastroduodenoscopy. The following portal hemodynamic parameters were analyzed: diameter and cross-sectional area, mean blood flow velocity, blood flow volume, perfusion pressure gradient, congestion index, and platelet count-to-spleen diameter ratio. Variceal characteristics, the size and the presence of red signs, were determined by endoscopic examination. RESULTS: Patients with variceal red signs had significantly higher values of portal diameter (1.538 +/- 0.246 vs. 1.243 +/- 0.167), cross-sectional area (1.286 +/- 0.448 vs. 0.945 +/- 0.256), blood flow volume (965.520 +/- 432.728 vs. 625.117 +/- 320.999) and congestion index (0.165 +/- 0.068 vs. 0.126 +/- 0.051) than patients without red signs, while the perfusion pressure gradient (0.260 +/- 0.087 vs. 0.447 +/- 0.271) and the platelet-to-spleen ratio (522.424 +/- 222.823 vs. 708.921 +/- 230.769) were lower. The same pattern of differences between the ultrasound parameters was found in patients with large varices comparing ones with red signs to the ones without them (diameter, 1.567 +/- 0.234 vs. 1.258 +/- 0.175; cross-section, 1.313 +/- 0.455 vs. 1.061 +/- 0.264; flow volume, 988.195 +/- 443.353 vs. 739.423 +/- 414.281; congestion index, 0.171 +/- 0.067 vs. 0.130 +/- 0.058; perfusion pressure gradient 0.247 +/- 0.078 vs. 0.501 +/- 0.379 and platelet-to-spleen ratio 479.930 +/- 184.302 vs. 699.094 +/- 316.171). Differences in values of ultrasonographic parameters were less obvious among groups of patients with different variceal sizes: only the diameter, cross-sectional area and blood flow volume were significantly different. The mean blood flow velocity did not depend on the variceal size or on the presence of red signs. The sensitivities and specificities of the analyzed parameters were 60-80% and 48.6-78.4%, respectively. CONCLUSIONS: Results suggest that color Doppler ultrasonography is a useful noninvasive method for evaluating the risk of esophageal variceal bleeding in patients with liver cirrhosis.     

The Association of Time to Organ Procurement on Short- and Long-Term Outcomes in Kidney Transplantation

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Estimation of C* Integral for Mismatched Welded Compact Tension Specimen

The C* integral for the compact tension (CT) specimen is calculated using the estimation equation in ASTM E1457-15. This equation was developed based on the assumption of material homogeneity and is not applicable to a welded CT specimen. In this paper, a modified equation for estimating the C* integral for a welded compact tension (CT) specimen under creep conditions is proposed. The proposed equation is defined on the basis of systematically conducted extensive finite element (FE) analyses using the ABAQUS program. A crack in the welded CT specimen is located in the center of the heat-affected zone (HAZ), because the most severe type IV cracks are located in the HAZ. The results obtained by the analysis show that the equation for estimating the C* integral in ASTM E1457-15 can underestimate the value of the C* integral for creep-soft HAZ and overestimate for creep-hard HAZ. Therefore, the proposed modified equation is suitable for describing the creep crack growth (CCG) of welded specimens.