Response of the Esophageal Epithelium to Concomitant Cis-Dichlorodiammineplatinum(II) and Radiation Treatment. An Electron Microscopic Study in Rabbits

The rabbit esophageal mucosa was irradiated with daily fractions of 2 Gy up to an accumulated dose of 20 Gy (total dose 2, 6, 10. 16 or 20 Gy). Fifteen to forty-five minutes before the start of each irradiation 0.3 mg Cis-dichlorodiammineplatinum (cis-DDP, cisplatinum) was given by intraperitoneal injection to each rabbit. Examinations were carried out 1-10 days after each fractionation schedule, when specimens were taken for morphological investigations. Scanning electron microscope (SEM) examination showed a gradual development of damage with cell loss and structural disarrangement of the microridges and whorls on the surface. However, with further treatment the esophageal mucosa exposed to cis-DDP and radiation normalized faster and more complete compared to the esophageal part exposed to cis-DDP alone. The difference may depend on an accelerated proliferation in the part of the trachea that is exposed to a combined treatment

The Response of the Tracheal Epithelium to Concomitant Cis-Diamminedichloroplatinum (II) and Radiation. An Electron Microscopic Study in Rabbits

The ciliated epithelium of the rabbit trachea was irradiated with daily fractions of 2 Gy up to an accumulated dose of 20 Gy (total dose: 2, 6, 10, 16, or 20 Gy). Fifteen to forty-five minutes before the start of each irradiation 0.3 mg Cis-diamminedichloroplatinum (cis-DDP) was given by intraperitoneal injection to each rabbit. Examinations were carried out 1-10 days after each fractionation schedule, when specimens were taken for morphological investigations. Scanning electron microscope (SEM) examination showed a gradual development of ciliary damage, from blebs on the cilia to swollen tips, broken and bent cilia and finally an epithelial injury with areas free from cilia, and a surface covered with microvilli-like structures. SEM also showed cell loss, and remnants of dead cells on the surface together with detritus. By transmission electron microscopy (TEM), ciliary damage, cell death and cell loss of the ciliated cell layer, as well as exfoliation of portions of goblet-like cells on the surface, could be confirmed. Scoring of SEM and TEM micro graphs showed that for the tracheal part treated with cis-DDP and radiation, the maximal damage was expressed in the dose group 10 Gy, and above this no further increase in the average reaction occurred. For the part of the trachea only exposed to cis-DDP, the damage increased with the dose. The difference observed speaks for an accelerated proliferation exerted by the radiation

The Effect of Ionizing Irradiation on Type I Collagen of the Tail in Growing Mice: A Histology and Electron Microscopy Study

In order to examine the effect of radiation on growing tissue, especially the fibroblasts and their end-product, the collagen fibres, tails from 24 mice were irradiated at an age of 8 days with 20 Gy and 30 Gy (\u3e°Co). Tails from 18 animals served as controls. Six mice from each group were sacrificed on day 8, 20 and 30. Transmission electron microscopy was used to examine the fibroblasts and the collagen fibrils. Non-irradiated fibroblasts had a nucleus rich in chromatin and an abundant endoplasmic reticulum with cistemae and condensing vacuoles. On day 20, approximately 50 % , and on day 30, 25 % of the fibroblasts irradiated with 30 Gy had a sparse endoplasmic reticulum pointing to a reduction of protein synthesis. While, on day 20, the fibrils irradiated with 20 Gy and with 30 Gy had significantly larger diameters compared to the controls, on day 30, the irradiated fibrils had a notably smaller diameter compared to the controls; 30 Gy-fibrils were larger than the 20 Gy-fibrils on both days. On day 20, the binding mean value of the 30 Gy-fibrils exceeded that of the controls and was significantly higher than that of the 20 Gy-fibrils, which was lower, though not significantly, than the controls. On day 30, the banding mean value of the 30 Gy-fibrils was notably lower than the control; and the value of the 20 Gy-fibrils was significantly lower than that of the 30 Gy-fibrils. The results are explained as an edema together with an inhibitory effect on the protein synthesis of the fibroblasts caused by the irradiation. This deduction 1s further supported by light microscopy of the tails

Scanning Electron Microscopy of Human Esophageal Mucosa in Patients with Carcinoma of the Esophagus

Specimens taken at surgery from 15 patients with carcinoma of the esophagus were examined with scanning electron microscopy. Nine patients were treated with chemotherapy (cisplatin + 5-fluorouracil), surgery and radiotherapy; one received preoperative radiotherapy only; and the remaining five primary surgery only. Scanning electron microscopy was performed on specimens of both tumor tissue and the mucosa at least 5 cm from the tumor. In adjacent non-tumor tissue, damage due to treatment was observed in the form of changes in microridges and increased cell loss. In tumor tissue, the degree of damage was correlated to tumor response to treatment. For patients with no residual tumor after treatment, the ultrastructure was normalized with a low tumor score, while for patients with residual tumor, the score was high

From Empowerment Dynamics to Team Adaptability: Exploring and Conceptualizing the Continuous Agile Team Innovation Process

To foster their innovation teams’ adaptability, organizations are increasingly relying on agile teams. While research on the adoption of agile methods and practices has grown tremendously in the past decade, little is currently known about the human side of agile teams and how it contributes toward the emergence of adaptability. While the Agile Manifesto states that individuals and interactions are more important for agile product development than tools and processes, research on how these interactions unfold is still in its infancy. To shed light on the human side of adaptability, 44 semi‐structured, in‐depth interviews were conducted with team members and leaders from various teams at three organizations (i.e., two German and one multinational European firm). The inductive analysis identified empowerment as a focal human factor for adaptability emergence. A model of the continuous agile team innovation process is developed and uncovers the importance of dynamic empowerment states and their temporary equilibria for team adaptability. The underlying findings demonstrate that empowerment is not a static state, but rather emerges through the interactions between various actors. Specifically, the team and its leader engage in both empowerment‐enhancing and empowerment‐reducing activities. These activities are further influenced by the agile team’s immediate context: Two‐fold customer influences, that is, supporting and hindering empowerment interactions, and the organizational environment, that is, undergoing an agile transformation and supportive top management behaviors, play an important role in affecting the empowerment dynamics that result in team adaptability. As such, this study contributes to the innovation and management literatures by revealing the dynamic role of the empowerment and adaptability constructs for agile innovation processes and the importance of various actors and the organizational environment for fostering adaptability. Practical insights are offered to management, teams, and team members on how to create conditions for empowerment dynamics and consequently adaptability to unfold

Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis

BACKGROUND: There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS. METHODS: A panel of neurodegenerative and neuroinflammatory markers were analyzed in repeated CSF samples from 41 patients with CIS or RRMS in a prospective longitudinal cohort study and from 22 healthy controls. NFL in serum was analyzed using a single-molecule array (Simoa) method. “No evidence of disease activity-3” (NEDA-3) status and brain volume (brain parenchymal fraction calculated using SyMRI®) were recorded during 4 years of follow-up. RESULTS: NFL levels in CSF and serum correlated significantly (all samples, n = 63, r 0.74, p < 0.001), but CSF-NFL showed an overall stronger association profile with NEDA-3 status, new T2 lesions, and brain volume loss. CSF-NFL was associated with both new T2 lesions and brain volume loss during follow-up, whereas CSF-CHI3L1 was associated mainly with brain volume loss and CXCL1, CXCL10, CXCL13, CCL22, and MMP-9 were associated mainly with new T2 lesions. CONCLUSIONS: Serum and CSF levels of NFL correlate, but CSF-NFL predicts and reflects disease activity better than S-NFL. CSF-NFL levels are associated with both new T2 lesions and brain volume loss. Our findings further add to the accumulating evidence that CSF-NFL is a clinically useful biomarker in CIS and RRMS and should be considered in the expanding NEDA concept. CSF-CXCL10 and CSF-CSF-CHI3L1 are potential markers of disease activity and brain volume loss, respectively

Very-High-Energy γ\gamma-Ray Observations of the Blazar 1ES 2344+514 with VERITAS

We present very-high-energy $\gamma$-ray observations of the BL Lac object 1ES 2344+514 taken by the Very Energetic Radiation Imaging Telescope Array System (VERITAS) between 2007 and 2015. 1ES 2344+514 is detected with a statistical significance above background of $20.8\sigma$ in $47.2$ hours (livetime) of observations, making this the most comprehensive very-high-energy study of 1ES 2344+514 to date. Using these observations the temporal properties of 1ES 2344+514 are studied on short and long times scales. We fit a constant flux model to nightly- and seasonally-binned light curves and apply a fractional variability test, to determine the stability of the source on different timescales. We reject the constant-flux model for the 2007-2008 and 2014-2015 nightly-binned light curves and for the long-term seasonally-binned light curve at the $> 3\sigma$ level. The spectra of the time-averaged emission before and after correction for attenuation by the extragalactic background light are obtained. The observed time-averaged spectrum above 200 GeV is satisfactorily fitted (${\chi^2/NDF = 7.89/6}$) by a power-law function with index $\Gamma = 2.46 \pm 0.06_{stat} \pm 0.20_{sys}$ and extends to at least 8 TeV. The extragalactic-background-light-deabsorbed spectrum is adequately fit (${\chi^2/NDF = 6.73/6}$) by a power-law function with index $\Gamma = 2.15 \pm 0.06_{stat} \pm 0.20_{sys}$ while an F-test indicates that the power-law with exponential cutoff function provides a marginally-better fit ($\chi^2/NDF$ = $2.56 / 5$) at the 2.1$\sigma$ level. The source location is found to be consistent with the published radio location and its spatial extent is consistent with a point source.Comment: 7 pages, 2 figures. Published in Monthly Notices of the Royal Astronomical Societ