Generation Z – Die Werte angehender Ärzte im Spannungsfeld zum künftigen Spitalalltag

The Swiss healthcare system has been undergoing a profound process of change for years, and is therefore in a rebuilding phase. Swiss hospitals are faced by considerable challenges including advancing digitalisation, enormous cost pressure and an increasing shortage of skilled workers. In the wake of this development, demographic changes continue, resulting in, on the one hand, noticeable ageing of the workforce and, on the other hand, a lack of young professionals, leading to problems in the maintenance of hospitals. For the latter, doctors play a central role and use their expertise to ensure that medical care continues to be provided. However, the medical profession is also struggling with the acquisition of young talents, and even today, are unable to fill many positions. Against this backdrop, Generation Z will be entering the hospital job market as a new age group in the coming years. The knowledge gained so far about this generation suggests that they sometimes work in a way that is fundamentally different to those that came before them, and this suggests that the working environment has to adapt to new events that have been, by and large, unknown to it thus far. This starting point prompted the author to research the values and job-related ideas of the up-and-coming doctors of Generation Z as part of a quantitative and qualitative study and to collect the data from medical students of human medicine from the medical faculties of the universities of Bern, Basel and Zurich. The knowledge gained is intended to show, on the one hand, the conditions under which Generation Z doctors can envisage a longer-term career as a hospital doctor, and on the other hand, the results should be made available to hospitals in the form of recommendations for action so that they can adapt their current working and employment conditions to the requirements of future Generation Z doctors in order to counteract the impending shortage of doctors. Against this backdrop, the research results obtained revealed interesting findings. The author was able to show, among other things, that Generation Z doctors can be acquired and retained in particular through "soft values" and that monetary incentives, for example, are hardly a motivation that will keep this age-group permanently satisfied in working life. It also emerged that family, friends and leisure time are often more important to this age group than professional careers, and these findings alone are likely to lead to significant changes in hospitals in the future

Analysis, Isolation, and Activation of Antigen-Specific CD4 + and CD8+ T Cells by Soluble MHC-Peptide Complexes

T cells constitute the core of adaptive cellular immunity and protect higher organisms against pathogen infections and cancer. Monitoring of disease progression as well as prophylactic or therapeutic vaccines and immunotherapies call for conclusive detection, analysis, and sorting of antigen-specific T cells. This is possible by means of soluble recombinant ligands for T cells, i.e., MHC class I-peptide (pMHC I) complexes for CD8(+) T cells and MHC class II-peptide (pMHC II) complexes for CD4(+) T cells and flow cytometry. Here we review major developments in the development of pMHC staining reagents and their diverse applications and discuss perspectives of their use for basic and clinical investigations

Anomalous Scale Dimensions from Timelike Braiding

Using the previously gained insight about the particle/field relation in conformal quantum field theories which required interactions to be related to the existence of particle-like states associated with fields of anomalous scaling dimensions, we set out to construct a classification theory for the spectra of anomalous dimensions. Starting from the old observations on conformal superselection sectors related to the anomalous dimensions via the phases which appear in the spectral decomposition of the center of the conformal covering group $Z(\widetilde{SO(d,2)}),$ we explore the possibility of a timelike braiding structure consistent with the timelike ordering which refines and explains the central decomposition. We regard this as a preparatory step in a new construction attempt of interacting conformal quantum field theories in D=4 spacetime dimensions. Other ideas of constructions based on the $AdS_{5}$-$CQFT_{4}$ or the perturbative SYM approach in their relation to the present idea are briefly mentioned.Comment: completely revised, updated and shortened replacement, 24 pages tcilatex, 3 latexcad figure

A novel HLA-B18 restricted CD8+ T cell epitope is efficiently cross-presented by dendritic cells from soluble tumor antigen

NY-ESO-1 has been a major target of many immunotherapy trials because it is expressed by various cancers and is highly immunogenic. In this study, we have identified a novel HLA-B*1801-restricted CD8<sup>+</sup>T cell epitope, NY-ESO-1<sub>88–96</sub> (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1<sub>157–165</sub> epitope restricted to HLA-A*0201. Although both epitopes were readily cross-presented by DCs exposed to various forms of full-length NY-ESO-1 antigen, remarkably NY-ESO-1<sub>88–96</sub> is much more efficiently cross-presented from the soluble form, than NY-ESO-1<sub>157–165</sub>. On the other hand, NY-ESO-1<sub>157–165</sub> is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A<sub>26–35</sub>; whereas NY-ESO-1<sub>88–96</sub> was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome. It was only presented when the tumor cells were first IFN-γ treated, followed by infection with recombinant vaccinia virus encoding NY-ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that the presentation of NY-ESO-1<sub>88–96</sub> is immunoproteasome dependent. Furthermore, a survey was conducted on multiple samples collected from HLA-B18+ melanoma patients. Surprisingly, all the detectable responses to NY-ESO-1<sub>88–96</sub> from patients, including those who received NY-ESO-1 ISCOMATRIX™ vaccine were induced spontaneously. Taken together, these results imply that some epitopes can be inefficiently presented by tumor cells although the corresponding CD8<sup>+</sup>T cell responses are efficiently primed in vivo by DCs cross-presenting these epitopes. The potential implications for cancer vaccine strategies are further discussed

A Prospective Pilot Study to Identify a Myocarditis Cohort who may Safely Resume Sports Activities 3 Months after Diagnosis

International cardiovascular society recommendations to return to sports activities following acute myocarditis are based on expert consensus in the absence of prospective studies. We prospectively enrolled 30 patients with newly diagnosed myocarditis based on clinical parameters, laboratory measurements and cardiac magnetic resonance imaging with mildly reduced or pre served left ventricular ejection fraction (LVEF) with a follow-up of 12 months. Cessation of physical activity was recommended for 3 months. The average age was 35 (19–80) years with 73% male patients. One case of non-sustained ventricular tachycardia was recorded during 48-h-Holter electrocardiogram. Except for this case, all patients were allowed to resume physical exercise after 3 months. At 6- (n = 26) and 12-month (n = 19) follow-up neither cardiac events nor worsening LVEF were recorded. The risk of cardiac events at 1 year after diagnosis of myocarditis appears to be low after resumption of exercise after 3 months among patients who recover from acute myocarditis

Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients-Report of a Phase I/IIa Clinical Trial.

PURPOSE: Cancer vaccines aim to generate and maintain antitumor immune responses. We designed a phase I/IIa clinical trial to test a vaccine formulation composed of Montanide ISA-51 (Incomplete Freund's Adjuvant), LAG-3Ig (IMP321, a non-Toll like Receptor agonist with adjuvant properties), and five synthetic peptides derived from tumor-associated antigens (four short 9/10-mers targeting CD8 T-cells, and one longer 15-mer targeting CD4 T-cells). Primary endpoints were safety and T-cell responses. EXPERIMENTAL DESIGN: Sixteen metastatic melanoma patients received serial vaccinations. Up to nine injections were subcutaneously administered in three cycles, each with three vaccinations every 3 weeks, with 6 to 14 weeks interval between cycles. Blood samples were collected at baseline, 1-week after the third, sixth and ninth vaccination, and 6 months after the last vaccination. Circulating T-cells were monitored by tetramer staining directly ex vivo, and by combinatorial tetramer and cytokine staining on in vitro stimulated cells. RESULTS: Side effects were mild to moderate, comparable to vaccines with Montanide alone. Specific CD8 T-cell responses to at least one peptide formulated in the vaccine preparation were found in 13 of 16 patients. However, two of the four short peptides of the vaccine formulation did not elicit CD8 T-cell responses. Specific CD4 T-cell responses were found in all 16 patients. CONCLUSIONS: We conclude that vaccination with IMP321 is a promising and safe strategy for inducing sustained immune responses, encouraging further development for cancer vaccines as components of combination therapies. Clin Cancer Res; 22(6); 1330-40. ©2015 AACR

Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK

Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history. Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted

High spatial resolution myocardial perfusion cardiac magnetic resonance for the detection of coronary artery disease

To evaluate the feasibility and diagnostic performance of high spatial resolution myocardial perfusion cardiac magnetic resonance (perfusion-CMR). Methods and results Fifty-four patients underwent adenosine stress perfusion-CMR. An in-plane spatial resolution of 1.4 x 1.4 mm(2) was achieved by using 5x k-space and time sensitivity encoding (k-t SENSE). Perfusion was visually graded for 16 left ventricular and two right ventricular (RV) segments on a scale from 0 = normal to 3 = abnormal, yielding a perfusion score of 0-54. Diagnostic accuracy of the perfusion score to detect coronary artery stenosis of >50% on quantitative coronary angiography was determined. Sources and extent of image artefacts were documented. Two studies (4%) were non-diagnostic because of k-t SENSE-related and breathing artefacts. Endocardial dark rim artefacts if present were small (average width 1.6 mm). Analysis by receiver-operating characteristics yielded an area under the curve for detection of coronary stenosis of 0.85 [95% confidence interval (CI) 0.75-0.95] for all patients and 0.82 (95% CI 0.65-0.94) and 0.87 (95% CI 0.75-0.99) for patients with single and multi-vessel disease, respectively. Seventy-four of 102 (72%) RV segments could be analysed. Conclusion High spatial resolution perfusion-CMR is feasible in a clinical population, yields high accuracy to detect single and multi-vessel coronary artery disease, minimizes artefacts and may permit the assessment of RV perfusion