Comparison of neoadjuvant cisplatin-based chemotherapy versus radiochemotherapy followed by resection for stage III (N2) NSCLC

Objective: Comparison of prospectively treated patients with neoadjuvant cisplatin-based chemotherapy vs radiochemotherapy followed by resection for mediastinoscopically proven stage III N2 non-small cell lung cancer with respect to postoperative morbidity, pathological nodal downstaging, overall and disease-free survival, and site of recurrence. Methods: Eighty-two patients were enrolled between January 1994 to June 2003, 36 had cisplatin and doxetacel-based chemotherapy (group I) and 46 cisplatin-based radiochemotherapy up to 44Gy (group II), either as sequential (25 patients) or concomitant (21 patients) treatment. All patients had evaluation of absence of distant metastases by bone scintigraphy, thoracoabdominal CT scan or PET scan, and brain MRI, and all underwent pre-induction mediastinoscopy, resection and mediastinal lymph node dissection by the same surgeon. Results: Group I and II comprised T1/2 tumors in 47 and 28%, T3 tumors in 45 and 41%, and T4 tumors in 8 and 31% of the patients, respectively (P=0.03). There was a similar distribution of the extent of resection (lobectomy, sleeve lobectomy, left and right pneumonectomy) in both groups (P=0.9). Group I and II revealed a postoperative 90-d mortality of 3 and 4% (P=0.6), a R0-resection rate of 92 and 94% (P=0.9), and a pathological mediastinal downstaging in 61 and 78% of the patients (P≪0.01), respectively. 5y-overall survival and disease-free survival of all patients were 40 and 36%, respectively, without significant difference between T1-3 and T4 tumors. There was no significant difference in overall survival rate in either induction regimens, however, radiochemotherapy was associated with a longer disease-free survival than chemotherapy (P=0.04). There was no significant difference between concurrent vs sequential radiochemotherapy with respect to postoperative morbidity, resectability, pathological nodal downstaging, survival and disease-free survival. Conclusions: Neoadjuvant cisplatin-based radiochemotherapy was associated with a similar postoperative mortality, an increased pathological nodal downstaging and a better disease-free survival as compared to cisplatin doxetacel-based chemotherapy in patients with stage III (N2) NSCLC although a higher number of T4 tumors were admitted to radiochemotherap

How to conceptualize and implement a PhD program in health sciences - the Basel approach

Over the past decade, several excellent guidelines have been published on how to enhance the quality of PhD education in Europe. Aimed primarily at preparing students for innovative roles in their fields, they include variously structured approaches to curricular offerings, as well as other program components applicable across specialties (eg: supervisor support, scientific conduct, transferable skills). Since 2012, the interdisciplinary PhD Program in Health Sciences (PPHS) at the Faculty of Medicine of the University of Basel in Switzerland has focused on translating these guidelines into a 21st-century health sciences PhD program.; The PPHS started in 2012 based on the European Union (EU) guidelines for PhD education. This article describes the resulting interdisciplinary PhD program's conceptual underpinnings, rationale, structures, and 10 building blocks, like student portfolios, thematic training, interdisciplinary research seminars, student-initiated interdisciplinary activities, financial support of course participation, top-up and extension stipends, PhD supervision, research integrity, alumni follow-up network, and promotional tools including a dedicated website. Students enter from Clinical Research, Medicine Development, Nursing Science, Epidemiology and Public Health including Insurance Medicine, Sport Science (all from the Faculty of Medicine), and Epidemiology (Faculty of Science).; The Basel PPHS exemplifies state-of-the-art PhD education in Health Sciences based on European guidelines and offers guidance to other groups from conceptualization to rollout of an interdisciplinary health sciences PhD program

Intense therapy in patients with locally advanced esophageal cancer beyond hope for surgical cure : a prospective, multicenter phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 76/02)

There is no standard treatment for patients with locally advanced esophageal carcinoma without systemic metastasis in whom surgery is no longer considered a reasonable option

How to Conceptualize and Implement a PhD Program in Health Sciences-The Basel Approach

Objectives: Over the past decade, several excellent guidelines have been published on how to enhance the quality of PhD education in Europe. Aimed primarily at preparing students for innovative roles in their fields, they include variously structured approaches to curricular offerings, as well as other program components applicable across specialties (eg: supervisor support, scientific conduct, transferable skills). Since 2012, the interdisciplinary PhD Program in Health Sciences (PPHS) at the Faculty of Medicine of the University of Basel in Switzerland has focused on translating these guidelines into a 21st-century health sciences PhD program. Results: The PPHS started in 2012 based on the European Union (EU) guidelines for PhD education. This article describes the resulting interdisciplinary PhD program's conceptual underpinnings, rationale, structures, and 10 building blocks, like student portfolios, thematic training, interdisciplinary research seminars, student-initiated interdisciplinary activities, financial support of course participation, top-up and extension stipends, PhD supervision, research integrity, alumni follow-up network, and promotional tools including a dedicated website. Students enter from Clinical Research, Medicine Development, Nursing Science, Epidemiology and Public Health including Insurance Medicine, Sport Science (all from the Faculty of Medicine), and Epidemiology (Faculty of Science). Discussion and Conclusion: The Basel PPHS exemplifies state-of-the-art PhD education in Health Sciences based on European guidelines and offers guidance to other groups from conceptualization to rollout of an interdisciplinary health sciences PhD program.status: publishe

Longitudinal TSPO expression in tau transgenic P301S mice predicts increased tau accumulation and deteriorated spatial learning.

BACKGROUND P301S tau transgenic mice show age-dependent accumulation of neurofibrillary tangles in the brainstem, hippocampus, and neocortex, leading to neuronal loss and cognitive deterioration. However, there is hitherto only sparse documentation of the role of neuroinflammation in tau mouse models. Thus, we analyzed longitudinal microglial activation by small animal 18 kDa translocator protein positron-emission-tomography (TSPO μPET) imaging in vivo, in conjunction with terminal assessment of tau pathology, spatial learning, and cerebral glucose metabolism. METHODS Transgenic P301S (n = 33) and wild-type (n = 18) female mice were imaged by 18F-GE-180 TSPO μPET at the ages of 1.9, 3.9, and 6.4 months. We conducted behavioral testing in the Morris water maze, 18F-fluordesoxyglucose (18F-FDG) μPET, and AT8 tau immunohistochemistry at 6.3-6.7 months. Terminal microglial immunohistochemistry served for validation of TSPO μPET results in vivo, applying target regions in the brainstem, cortex, cerebellum, and hippocampus. We compared the results with our historical data in amyloid-β mouse models. RESULTS TSPO expression in all target regions of P301S mice increased exponentially from 1.9 to 6.4 months, leading to significant differences in the contrasts with wild-type mice at 6.4 months (+ 11-23%, all p < 0.001), but the apparent microgliosis proceeded more slowly than in our experience in amyloid-β mouse models. Spatial learning and glucose metabolism of AT8-positive P301S mice were significantly impaired at 6.3-6.5 months compared to the wild-type group. Longitudinal increases in TSPO expression predicted greater tau accumulation and lesser spatial learning performance at 6.3-6.7 months. CONCLUSIONS Monitoring of TSPO expression as a surrogate of microglial activation in P301S tau transgenic mice by μPET indicates a delayed time course when compared to amyloid-β mouse models. Detrimental associations of microglial activation with outcome parameters are opposite to earlier data in amyloid-β mouse models. The contribution of microglial response to pathology accompanying amyloid-β and tau over-expression merits further investigation

Magnetic behavior of trioctahedral micas with different octahedral Fe ordering

This contribution is finalized at the discussion of the magnetic structure of two samples, belonging to phlogopite\u2013annite [sample TK, chemical composition IV(Si2.76Al1.24) VI(Al0.64Mg0.72 Fe1.452+ Mn0.03Ti0.15) (K0.96Na0.05) O10.67 (OH)1.31 Cl0.02] and polylithionite\u2013siderophyllite joints [sample PPB, chemical composition IV(Si3.14Al0.86)VI(Al0.75Mg0.01 Fe1.032+ Fe1.033+ Mn0.01Ti0.01Li1.09) (K0.99Na0.01) O10.00 (OH)0.65F1.35]. Samples differ for Fe ordering in octahedral sites, Fe2+/(Fe2+ + Fe3+) ratio, octahedral composition, defining a different environment around Fe cations, and layer symmetry. Spin-glass behavior was detected for both samples, as evidenced by the dependency of the temperature giving the peak in the susceptibility curve from the frequency of the applied alternating current magnetic field. The crystal chemical features are associated to the different temperature at which the maximum in magnetic susceptibility is observed: 6 K in TK, where Fe is disordered in all octahedral sites, and 8 K in PPB sample, showing a smaller and more regular coordination polyhedron for Fe, which is ordered in the trans-site and in one of the two cis-sites