8 research outputs found
Diagnostic, Clinical and Post-SARS-CoV-2 Scenarios in Cancer Patients with SARS-CoV-2: Retrospective Analysis in Three German Cancer Centers.
No full textOncologists face challenges in the management of SARS-CoV-2 infections and post-SARS-CoV-2 cancer treatment. We analyzed diagnostic, clinical and post-SARS-CoV-2 scenarios in patients from three German cancer centers with RT-PCR confirmed SARS-CoV-2 infection. Sixty-three patients with SARS-CoV-2 and hematologic or solid neoplasms were included. Thirty patients were initially asymptomatic, 10 of whom developed COVID-19 symptoms subsequently. Altogether 20 (32%) patients were asymptomatic, 18 (29%) had mild, 12 (19%) severe and 13 (20%) critical courses. Lymphocytopenia increased risk of severe/critical COVID-19 three-fold (p = 0.015). Asymptomatic course was not associated with age, remission status, therapies or co-morbidities. Secondary bacterial infection accompanied more than one third of critical COVID-19 cases. Treatment was delayed post-SARS-CoV-2 in 46 patients, 9 of whom developed progressive disease (PD). Cancer therapy was modified in 8 SARS-CoV-2 survivors because of deteriorating performance or PD. At the last follow-up, 17 patients had died from COVID-19 (n = 8) or PD (n = 9) giving an estimated 73% four-month overall survival rate. SARS-CoV-2 infection has a heterogenous course in cancer patients. Lymphocytopenia carries a significant risk of severe/critical COVID-19. SARS-CoV-2 disruption of therapy is as serious as SARS-CoV-2 infection itself. Careful surveillance will allow early restart of the anti-cancer treatment
Impact of pre-OP independence in patients with limited brain metastases on long-term survival
No full textBackground Brain metastasis represents a major complication with a significantly shorter overall survival of many oncological diseases, in particular of lung cancer, breast cancer and malignant melanoma patients. However, despite the poor prognosis, sometimes clinical decision-making, between on the one hand not to harm the patient and on the other hand not withholding a potential therapeutic option, is very challenging. Thus the aim of this retrospective study was to compare various scores, including scores for activities of daily living (ADL) before resection of brain metastases and to analyse their impact on survival. Methods Our single institution retrospective patient cohort (N = 100) with a median age of 63.6 years, which had all undergone resection of one or more brain metastases, was categorized using the original patient files. The cohort includes 52 patients with lung cancer, 27 patients with breast cancer, 8 patients with colorectal carcinoma and 13 patients with kidney cancer. To categorize, we used different score systems which were capable to evaluate the patient in relation to self-sufficiency, activity and self-determination as part of ADL. The retrospective analysis includes the ECOG-Status, Karnofsky-Index, Barthel-Index, ASA-Classification and Katz-Index. Pre-processing and the analysis of the data was implemented using KNIME, where we used the R-plugin nodes to perform the final statistical tests with R. Results Our analysis reveals that most of the ADL scores we tested are able to give a reliable prediction on overall survival after brain metastasis surgery. The survival rates decrease significantly with a lower score in all tested score systems, with the exception of the ASA-Risk score. In particular, the Katz Index < 6 was identified to have a significant correlation with a lower cancer specific survival (CSS) (HR 3.33, 95%-CI [2.17-5.00];p-Value = 9.6*10(- 9)), which is easy to use and has reproducible measurements. Conclusions Pre-operative independence assessment by indices of ADL represents a predictor for overall survival after resection of brain metastases. Especially the easily, objectively and rapidly applicable Katz-Score is a very helpful tool to assess the pre-operative status, which could be additionally included in clinical decision making in daily practice
Die Rolle des Protein-Phosphatase Inhibitor 1 in der initialen Phase nach der transversen Aortenkonstriktion im Mausmodel
No full textPhosphatase inhibitor-1-deficient mice are protected from catecholamine-induced arrhythmias and myocardial hypertrophy
No full textPhosphatase inhibitor-1 (I-1) is a conditional amplifier of beta-adrenergic signalling downstream of protein kinase A by inhibiting type-1 phosphatases only in its PKA-phosphorylated form. I-1 is downregulated in failing hearts and thus contributes to beta-adrenergic desensitization. It is unclear whether this should be viewed as a predominantly adverse or protective response. We generated transgenic mice with cardiac-specific I-1 overexpression (I-1-TG) and evaluated cardiac function and responses to catecholamines in mice with targeted disruption of the I-1 gene (I-1-KO). Both groups were compared with their wild-type (WT) littermates. I-1-TG developed cardiac hypertrophy and mild dysfunction which was accompanied by a substantial compensatory increase in PP1 abundance and activity, confounding cause-effect relationships. I-1-KO had normal heart structure with mildly reduced sensitivity, but unchanged maximal contractile responses to beta-adrenergic stimulation, both in vitro and in vivo. Notably, I-1-KO were partially protected from lethal catecholamine-induced arrhythmias and from hypertrophy and dilation induced by a 7 day infusion with the beta-adrenergic agonist isoprenaline. Moreover, I-1-KO exhibited a partially preserved acute beta-adrenergic response after chronic isoprenaline, which was completely absent in similarly treated WT. At the molecular level, I-1-KO showed lower steady-state phosphorylation of the cardiac ryanodine receptor/Ca(2+) release channel and the sarcoplasmic reticulum (SR) Ca(2+)-ATPase-regulating protein phospholamban. These alterations may lower the propensity for diastolic Ca(2+) release and Ca(2+) uptake and thus stabilize the SR and account for the protection. Taken together, loss of I-1 attenuates detrimental effects of catecholamines on the heart, suggesting I-1 downregulation in heart failure as a beneficial desensitization mechanism and I-1 inhibition as a potential novel strategy for heart failure treatment
Description of the KNMI Operational Wave Forecast Model GONO
No full textThe purpose of this report is to give a description of the GONO computercode, which is operational at KNMI for many years now. The program was developed by J.W. Sanders, and its deep water version is based on a Norwegian wave prediction model. built by C. Haug in the sixties. Shallow water effects are however important in the southern part of the North Sea. giving a limitation of the wave growth and causing important swell dissipation. A discussion of the shallow water effects. as present in GONO, is given by Sanders in Ref. 3. The computer code GONO is written in ALGOL60 and operational on the Burroughs 6700 of KNMI. The program GONO calculates wind speed. wind direction and sea energy at every grid point of the GONO grid (cf. Appendix A) and swell energy at a limited number of points only (we call these points swell points). GONO runs every six hours and it gives a 12 and 24 hours forecast as well as results based on analyzed weather maps. In the winter of '79-'80 the output of GONO was compared with measurements and the operational wave model of Bracknell (United Kingdom). (The latter GONO version differs a little bit from the version here described). The preliminary results of this comparison are given in Ref. 4. A reasonable agreement of significant wave height and low-frequency energy, as given by GONO, with the observations was found. The present version of GONO, with small modifications compared to the previous version, is operational since the end of February 1980. Essentially, the GONO model is based on two steps. First. the sea energy at every grid point is determined. To this end advection of energy is treated by means of a finite difference scheme whereas the growth of the wave energy is calculated by means of an empirical growth curve (assuming that the wave spectrum has a fixed form). The second step is the calculation of the swell. Of course, in principle swell can be treated likewise, but then one has to store swell energy (and its direction) at every time, at every grid point for every frequency band. Also. this finite difference scheme is rather crude for swell propagation. whereas. because of stability reasons. there is an upper bound for the propagation speed (in the present case the upper bound is given by 13.87 m/s). If one is only interested in swell information at particular points (swell points), it is tempting to use a ray technique. The advantage of this technique is that it is very accurate. Swell is determined in this fashion in GONO.GON
Impact of pre-OP independence in patients with limited brain metastases on long-term survival
No full textBackground: Brain metastasis represents a major complication with a significantly shorter overall survival of many oncological diseases, in particular of lung cancer, breast cancer and malignant melanoma patients. However, despite the poor prognosis, sometimes clinical decision-making, between on the one hand not to harm the patient and on the other hand not withholding a potential therapeutic option, is very challenging. Thus the aim of this retrospective study was to compare various scores, including scores for activities of daily living (ADL) before resection of brain metastases and to analyse their impact on survival.
Methods: Our single institution retrospective patient cohort (N = 100) with a median age of 63.6 years, which had all undergone resection of one or more brain metastases, was categorized using the original patient files. The cohort includes 52 patients with lung cancer, 27 patients with breast cancer, 8 patients with colorectal carcinoma and 13 patients with kidney cancer. To categorize, we used different score systems which were capable to evaluate the patient in relation to self-sufficiency, activity and self-determination as part of ADL. The retrospective analysis includes the ECOG-Status, Karnofsky-Index, Barthel-Index, ASA-Classification and Katz-Index. Pre-processing and the analysis of the data was implemented using KNIME, where we used the R-plugin nodes to perform the final statistical tests with R.
Results: Our analysis reveals that most of the ADL scores we tested are able to give a reliable prediction on overall survival after brain metastasis surgery. The survival rates decrease significantly with a lower score in all tested score systems, with the exception of the ASA-Risk score. In particular, the Katz Index < 6 was identified to have a significant correlation with a lower cancer specific survival (CSS) (HR 3.33, 95%-CI [2.17–5.00]; p-Value = 9.6*10^− 9), which is easy to use and has reproducible measurements.
Conclusions: Pre-operative independence assessment by indices of ADL represents a predictor for overall survival after resection of brain metastases. Especially the easily, objectively and rapidly applicable Katz-Score is a very helpful tool to assess the pre-operative status, which could be additionally included in clinical decision making in daily practice
The principles of screen design for computer-based learning materials.
No full textThe critical interface between learners and computer-based learning materials is the
screen. If the display of learning is not effective then learning will be hindered.
Screen design is therefore an important element in the design of computer-based
learning.
This research investigated the three fundamental screen design elements of
text, colour and graphics. A review of literature, experimental design and a limited
survey of computer-based learning materials provided the background for this
research. The experimental materials reflected the results of the review and survey
by using representative subjects, providing a learning focus and employing computerbased materials. Two experiments were undertaken. The Colour and Graphics
experiments considered the effects of a number of variables on learners' behaviour
which included: the use of colour; the size and type of graphics; the learner's prior
knowledge of tutorial subject; and the complexity of the display.
The results of this research showed that colour is a powerful motivating force
as long as it is not used excessively. This was identified as the use of more than
seven colours. Graphics can be used more extensively in current computer-based
learning materials and users preferred representational graphics occupying a quarter
to a half of the screen. However, learners were not prepared to make the effort to
either use analogical graphics to make links with their prior knowledge or to extract
information contained in the structure and form of logical graphics. Subjects were
motivated by representational graphics.
Learners' behaviour in relation to the various screen displays they
encountered was affected by their prior knowledge of the tutorial content. This was
apparent in their choice of options (additional modules) within the tutorial, their
methods of interacting with the material and their responses to individual displays
Religious intellectuals : the poetic gravity of Emily Brontë and Christina Rossetti
No full textThis thesis examines the writing of Emily Brontë and Christina Rossetti in terms of its
expression of religious culture and belief. It is my argument that Brontë and Rossetti
experienced religion as intellectuals, questioning and exploring doctrine and dogma neither
as sentimental lady Christians nor dismissive, secular critics. I contend that by close
reading their poetry, the genre both women privileged as most appropriate for the
consideration of religious matters, the reader may trace the sermons and theological works
they read. Moreover, their writing, I suggest, evinces their intellectual response to
theological, ecclesiological and ecclesiastical developments that took place in the
nineteenth century. I thus label Brontë and Rossetti 'religious intellectuals,' a phrase
suggestive of their intense understanding of, rather than their mild acquaintance with,
religious debate. Many women writing within the nineteenth century found that religion
granted them a field within which to freely read and research, but were denied the
professional title of 'theologian.' Brontë and Rossetti are thus examples of a wider
phenomenon wherein women encountered religion like scholars, one disregarded by current
criticism unable as it is to categorize a female activity simultaneously religious and
intellectual. I use Brontë and Rossetti as examples of what I call the 'religious intellectual'
because they represent different sides of this classification. Where Brontë struggled away
from her Methodist background, serving as a cultural commentator on its enthusiastic
belief-system, Rossetti forged a scholarly identity as a late member of the High Church
Oxford Movement. Both poets, I contend, wrote about religion in order to signal their
intellectual ability. I conclude that Brontë's interest in Methodism and Rossetti's
fascination with Tractarianism reveals the poets to be both independent of family pressures
and false consciousness, and fully engaged with a subject central to their age
