Transformation, Politics and Implementation

Working in environments characterised by a high degree of uncertainty, uncontrollability and unpredictability, development agents try to organise complex realities into manageable units. What principles influence the decision on adequate approaches and necessary steps

Helicopter inter-hospital transfer for patients undergoing extracorporeal membrane oxygenation: a retrospective 12-year analysis of a service system.

BACKGROUND Patients undergoing extracorporeal membrane oxygenation (ECMO) are critically ill and show high mortality. Inter-hospital transfer of these patients has to be safe, with high survival rates during transport without potentially serious and life-threatening adverse events. The Swiss Air-Rescue provides 24-h/7-days per week inter-hospital helicopter transfers that include on-site ECMO cannulation if needed. This retrospective observational study describes adverse events of patients on ECMO transported by helicopter, and their associated survival. METHODS All patients on ECMO with inter-hospital transfer by helicopter from start of service in February 2009 until May 2021 were included. Patients not transported by helicopter or with missing medical records were excluded. Patient demographics (age, sex) and medical history (type of and reason for ECMO), mission details (flight distance, times, primary or secondary transport), adverse events during the inter-hospital transfer, and survival of transferred patients were recorded. The primary endpoint was patient survival during transfer. Secondary endpoints were adverse events during transfer and 28-day survival. RESULTS We screened 214 ECMO-related missions and included 191 in this analysis. Median age was 54.6 [IQR 46.1-62.0] years, 70.7% were male, and most patients had veno-arterial ECMO (56.5%). The main reasons for ECMO were pulmonary (46.1%) or cardiac (44.0%) failure. Most were daytime (69.8%) and primary missions (n = 100), median total mission time was 182.0 [143.0-254.0] min, and median transfer distance was 52.7 [33.2-71.1] km. All patients survived the transfer. Forty-four adverse events were recorded during 37 missions (19.4%), where 31 (70.5%) were medical and none resulted in patient harm. Adverse events occurred more frequently during night-time missions (59.9%, p = 0.047). Data for 28-day survival were available for 157 patients, of which 86 (54.8%) were alive. CONCLUSION All patients under ECMO survived the helicopter transport. Adverse events were observed for about 20% of the flight missions, with a tendency during the night-time flights, none harmed the patients. Inter-hospital transfer for patients undergoing ECMO provided by 24-h/7-d per week helicopter emergency medical service teams can be considered as feasible and safe. The majority of the patients (54.8%) were still alive after 28 days

Seasonal variations in the diagnosis of testicular germ cell tumors: a national cancer registry study in austria

SIMPLE SUMMARY: Seasonal variations in cancer diagnosis could already be demonstrated in prostate and breast cancer. The reasons for this observed seasonal pattern are still unclear. The health care system or other determinants such as the protective function of vitamin D3 in carcinogenesis could be assumed as one explanation. Testicular germ cell tumors are the most common developed malignancy among young men. The aim of our study was to investigate, for the first time, the seasonal variations in the clinical diagnosis of testicular germ cell tumors. We have been able to confirm that the frequency of monthly newly diagnosed cases of testicular cell tumors in Austria has a strong seasonality, with a significant reduction in the tumor incidence during the summer months and an increase during the winter months. ABSTRACT: We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr–Sep) and an increase during the winter months (Oct–Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct–Dec (p = 0.008) and Jan–Mar (p < 0.001) was significantly higher compared to the months of Jul–Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research

translation with d-amino acids

Key components of the translational apparatus, i.e. ribosomes, elongation factor EF-Tu and most aminoacyl-tRNA synthetases, are stereoselective and prevent incorporation of d-amino acids (d-aa) into polypeptides. The rare appearance of d-aa in natural polypeptides arises from post-translational modifications or non-ribosomal synthesis. We introduce an in vitro translation system that enables single incorporation of 17 out of 18 tested d-aa into a polypeptide; incorporation of two or three successive d-aa was also observed in several cases. The system consists of wild-type components and d-aa are introduced via artificially charged, unmodified tRNAGly that was selected according to the rules of ‘thermodynamic compensation’. The results reveal an unexpected plasticity of the ribosomal peptidyltransferase center and thus shed new light on the mechanism of chiral discrimination during translation. Furthermore, ribosomal incorporation of d-aa into polypeptides may greatly expand the armamentarium of in vitro translation towards the identification of peptides and proteins with new properties and functions

Treatment intensification in HIV-infected Patients is associated With reduced Frequencies of regulatory T cells

In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved. Treatment strategies to avoid the induction of these cells preserve immune functions and are therefore the object of intense research efforts. In this study, we assessed the effect of treatment intensification [= 5-drug antiretroviral therapy (ART)] on the development of suppressive cell subsets. The New Era (NE) study recruited patients with primary HIV infection (PHI) or chronically HIV-infected patients with conventional ART (CHI) and applied an intensified 5-drug regimen containing maraviroc and raltegravir for several years. We compared the frequencies of the immune suppressive cells, namely, the myeloid-derived suppressor cells (MDSCs), regulatory B cells (Bregs), and regulatory T cells (Tregs), of the treatment intensification patients to the control groups, especially to the patients with conventional 3-drug ART, and analyzed the Gag/Nef-specific CD8 T cell responses. There were no differences between PHI and CHI in the NE population (p > 0.11) for any of the studied cell types. Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic myeloid-derived suppressor cell (M-MDSC), and the Breg frequencies were comparable to those of patients with a 3-drug ART. However, the Treg levels were significantly lower in the NE patients than those in 3ART-treated individuals and other control groups (p = 0.0033). The Gag/Nef-specific CD8 T cell response was broader (p = 0.0134) with a higher magnitude (p = 0.026) in the NE population than that in the patients with conventional ART. However, we did not find a correlation between the frequency of the immune suppressive cells and the interferon-gamma+ CD8 T cell response. In the treatment intensification subjects, the frequencies of the immune suppressive cells were comparable or lower than those of the conventional ART-treated subjects, with surprisingly broad HIV-specific CD8 T cell responses, suggesting a preservation of immune function with the applied treatment regimen. Interestingly, these effects were seen in both treatment intensification subpopulations and were not attributed to the start of treatment in primary infection

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Remigration und Islamisierung auf dem aegyptischen Dorf Forschungshypothesen

UuStB Koeln(38)-890107134 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman