SummaryNew drug combinations against falciparum malaria which are both effective and affordable for Sub-Saharan African populations are urgently needed. The combination of the well-known drugs chloroquine (CQ) and methylene blue (MB) is such a promising new regimen. However, there is some concern that MB could cause development of haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a condition which is prevalent in malaria-endemic regions. Against this background, 74 G6PD-deficient but otherwise healthy adult men were given a 3-day oral regimen of a total of 1500 mg CQ and 780 mg MB in the District Hospital of Nouna in northwestern Burkina Faso. Haemolysis did not occur, haemoglobin levels remained stable or even rose in the study participants, and the drug regimen was well tolerated. Therefore, standard dosages of MB appear to be safe in G6PD-deficient African populations with predominantly class III G6PD deficiency.keywords methylene blue, malaria, G6PD deficiency, Africa
Lactate dehydrogenase (LDH) in serum has recently been introduced into the American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma because of its prognostic value. We hypothesised LDH to be of value in discriminating melanoma patients entering AJCC stage IV from patients staying in AJCC stages I, II or III. Lactate dehydrogenase was compared to the acute phase protein C-reactive protein (CRP), which we observed to reflect the course of melanoma metastasis in a previous report. In this prospective study, we measured LDH and CRP in the serum of 91 consecutive melanoma patients progressing into AJCC stage IV in comparison to 125 patients staying in AJCC stages I, II or III. Comparing distributions of the parameters by median values and quartiles by Mann -Whitney test, LDH was not significantly elevated in patients entering AJCC stage IV melanoma (P ¼ 0.785), whereas CRP was (Po0.001). Analysing the sensitivity and the specificity jointly by the areas under the receiver operating characteristics curves (ROC-AUC), LDH did not discriminate between the defined groups of patients (AUC ¼ 0.491; 95% confidence interval, 0.410, 0.581), whereas CRP did (AUC ¼ 0.933; 95% confidence interval, 0.900, 0.966; Po0.001). Upon logistic regression analysis to calculate the ROC-AUC values upon the predictive probabilities, LDH provided no additional information to CRP. Choosing a cutoff point of 3.0 mg l À1 , CRP yielded a sensitivity of 0.769 together with a specificity of 0.904 in diagnosing AJCC stage IV entry. Altogether, for first diagnosing AJCC stage IV melanoma, CRP is the superior serum marker when compared to the conventional LDH.
ABSTRACT. Students' career preferences are an important issue to various stakeholders: to university administration, career counselors, higher education policy makers as well as to human resource managers in companies. Students, whose career preferences and goals are fulfilled, are better and more highly motivated employees. By a questionnaire survey carried out in 2016 in two institutions of higher education the present study compares career preferences and attitudes of 478 German and Croatian students. Factor analyses identify latent variables behind students' preferences. The identified significant differences between the Germans and Croatians are related to differences in socio-economic environment and cultural differences derived through the Hofstede model. German students value safe jobs, trust and a high income significantly more, whereas for Croatian students stimulating tasks, career opportunities, a recognized profession and social responsibility are more important. Our results indicate that Hofstede's findings for the uncertainty avoidance index and the individualism/collectivism index might be questioned for the subsample of a young student population who show different value criteria in their career preferences. JEL Classification: J24
Downstream of Ras, the serine/threonine kinase, B-raf, has recently been reported to be mutated, among other carcinomas, in a substantial subset of primary melanomas with a preponderance of the oncogenic V599E transition. As the risk of melanoma is enhanced by intermittent ultraviolet (UV) exposure but is less with chronic UV exposure, we here studied B-raf kinase domain (exon 15) mutations in primary cutaneous melanomas with respect to anatomical locations reflecting chronic versus intermittent UV exposure. Investigating a representative number of 101 primary melanoma resection specimens for the presence of mutations within the activation segment (exon 15) of the B-raf kinase domain by polymerase chain reaction and single-strand conformation polymorphism gel electrophoresis, followed by DNA cloning and sequencing, we found 32 cases (32%) which harbour somatic B-raf exon 15 mutations. As to the B-raf protein sequence, the V599E mutation was predicted in 66% of these positive melanomas, followed in frequency by the V599K transition (16%). Only two C➝T transitions, considered to be induced by UV irradiation, occurred in two melanomas located on the head. Among 23 melanomas located at body sites with chronic UV exposure, only a single tumour harboured the B-raf V599E mutation (4%), which was a significantly lower frequency in comparison to melanomas from sun-protected body sites (26%; Fisher's exact test, p=0.038; odds ratio, 7.59). Our observation parallels the epidemiological data of intermittent sunlight exposure on unacclimatised skin increasing the risk of melanoma development.
Clinical trials are often planned with high uncertainty about the variance of the primary outcome variable. A poor estimate of the variance, however, may lead to an over-or underpowered study. In the internal pilot study design, the sample variance is calculated at an interim step and the sample size can be adjusted if necessary. The available recalculation procedures use the data of those patients for sample size recalculation that have already completed the study. In this article, we consider a variance estimator that takes into account both the data at the endpoint and at an intermediate point of the treatment phase. We derive asymptotic properties of this estimator and the relating sample size recalculation procedure. In a simulation study, the performance of the proposed approach is evaluated and compared with the procedure that uses only long-term data. Simulation results demonstrate that the sample size resulting from the proposed procedure shows in general a smaller variability. At the same time, the Type I error rate is not inflated and the achieved power is close to the desired value.
The purpose of this study was to determine sensitivity and specificity of the modified Evans blue dye test (MEBDT) in tracheostomised patients after treatment of head and neck squamous cell carcinoma (HNSCC). This was a prospective study with 30 consecutive patients. All individuals underwent a MEBDT and a subsequent fiberoptic endoscopic evaluation of swallowing (FEES) immediately after the MEBDT for reconsidering the validity of the MEBDT. Aspiration was present in 20 patients documented by MEBDT and FEES. One patient was judged to aspirate by FEES but not by MEBDT (1 false-negative result). Nine patients showed no aspiration either by MEBDT or by FEES. The sensitivity of the MEBDT protocol in predicting aspiration among individuals in our cohort was 95.24%, the specificity 100%, respectively. The results of the current investigation suggest that the MEBDT is much more sensitive in tracheostomised HNSCC patients than in tracheostomised neurological patients. The MEBDT for tracheostomised HNSCC patients offers a quick and reliable method to identify aspiration risk in cases of severe dysphagia.
The aim of this study was to evaluate leakage of liquids, i.e., water and saliva, past low-pressure cuffs of tracheostomy tubes. Three different types of tracheostomy tubes, TRACOE vario (TRACOE Medical GmbH, Germany), Rüsch Ultra-Tracheoflex (Rüsch GmbH, Germany), and Portex Blue Line Ultra (Smiths Medical, UK) were tested in isolated pig tracheas. Sixty samples (10 tubes each of 7- and 8-mm inner diameter of each type) were used. Four different experiments were devised: type 1 (water and artificial ventilation), type 2 (water and no artificial ventilation), type 3 (saliva and artificial ventilation), and type 4 (saliva and no artificial ventilation). Six milliliters of water or artificial saliva were infused over the cuff and the volume of fluid that leaked past the cuff was measured after 5, 10, and 15 min. Intracuff pressure was also measured three times. The saliva experiments resulted in less leakage than the water experiments. Leakage after treatment with water or artificial saliva is higher without artificial ventilation than with ventilation. The amount of leakage among the tubes with respect to manufacturer showed statistically significant results. However, there were no differences among tracheostomy tubes with respect to internal diameter.
Students tend to be overconfident about their future performance in university exams, which can lead to demotivation when faced with unexpectedly bad results. We hypothesized that overconfidence is partly a personality trait but also partly results from students’ insufficient knowledge of what is expected of them in university exams. It follows that this should decrease as the students learn what is really required. In a longitudinal study with 441 students from a southern German university, we asked students to solve intelligence test questions and to make estimates of their own performances. Additionally, students estimated their performance in a forthcoming maths and/or a descriptive statistics exam. Then shortly after the exam was taken they indicated their planned and effective hours of study. As expected, students did not, in the mean, overestimate their performance on intelligence test questions. Women were more likely than men to underestimate their performance. Over‐ or underestimation in intelligence test questions did, however, predict misestimation in the mathematics and the statistics exams. Also, further correlations of misestimation between the statistics and a financial mathematics exam could be found—as such misestimation can be interpreted to be a stable trait. Students with an "Abitur" qualification were more likely to underestimate their performance, while students with other preuniversity qualifications tended to overestimate their performance. No effect of personality factors was found. Against our expectations, students who had overestimated themselves later indicated a higher number of hours studied than other students. We suggest different strategies by which students and universities can actively counter overestimation.
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