The Impact of Decision Makers’ Constraints on the Outcome of Value of Information Analysis

Background

When proven effective, decision making regarding reimbursement of new health technology typically involves ethical, social, legal, and health economic aspects and constraints. Nevertheless, when applying standard value of information (VOI) analysis, the value of collecting additional evidence is typically estimated assuming that only cost-effectiveness outcomes guide such decisions.

Zur Lehre von den Flüssigkeitsströmungen im lebenden Auge und in den Geweben überhaupt

Ohne ZusammenfassungHierzu Taf. XX. Fig. 1–2.     

Natural antibodies that react with V-region peptide epitopes of DNA-binding antibodies are made by mice with systemic lupus erythematosus as disease develops.

Cross-reactive idiotypes (CRI) have been detected on anti-DNA autoantibodies associated with lesions typical of systemic lupus erythematosus. In order to analyse the antigenic make up of idiotypes on anti-DNA monoclonal antibodies (mAb) V-88 (IgG1 kappa) and F-423 (IgG3 kappa), derived respectively from an adult (NZB x NZW)F1 and a fetal MRL/Mp-lpr/lpr mouse, a set of overlapping hexapeptides representing the VH and VL regions of mAb V-88 and F-423 were synthesized and reacted with a range of sera in pepscan enzyme-linked immunosorbent assays (ELISA) taken from normal and lupus mouse strains. Serum pools were collected both from normal BALB/c and lupus MRL/Mp-lpr/lpr and (NZB x NZW)F1 mice at 10, 20 and 30 weeks of age and analysed for the presence of spontaneously produced anti-V-region peptide IgM and IgG antibodies. IgM antibodies from both the lupus mice reacted with the same V-region epitopes, and although some epitopes mapped to similar locations in the two mAb, the maps for V-88 and F-423 were not identical. In MRL/Mp-lpr/lpr mice, as lupus disease progressed there was a switch from IgM antibodies to IgG anti-peptide antibodies whose specificity for the peptide antigens coincided with but was better defined than that of the IgM antibodies. The identified idiotopes were located in both complementary determining regions (CDR) and framework region (FR) regions, indicating that some contribute to CRI shared by other related antibodies, while others were unique to either mAb V-88 or F-423. In conclusion, we have dissected and identified a mosaic of antibody V-region idiotopes that contribute to the idiotype of an anti-DNA autoantibody and against which autoantibodies are made naturally in lupus disease.     

Regulation of endothelial monocyte-activating polypeptide II release by apoptosis

Endothelial monocyte-activating polypeptide II (EMAP II) is a proinflammatory cytokine and a chemoattractant for monocytes. We show here that, in the mouse embryo, EMAP II mRNA was most abundant at sites of tissue remodeling where many apoptotic cells could be detected by terminal deoxynucleotidyltransferase-mediated dUTP end labeling. Removal of dead cells is known to require macrophages, and these were found to colocalize with areas of EMAP II mRNA expression and programmed cell death. In cultured cells, post-translational processing of pro-EMAP II protein to the mature released EMAP II form (23 kDa) occurred coincidentally with apoptosis. Cleavage of pro-EMAP II could be abrogated in cultured cells by using a peptide-based inhibitor, which competes with the ASTD cleavage site of pro-EMAP II. Our results suggest that the coordinate program of cell death includes activation of a caspase-like activity that initiates the processing of a cytokine responsible for macrophage attraction to the sites of apoptosis.     

Complications After Ostomy Surgery: Emergencies and Obese Patients are at Risk—Data from the Berlin OStomy Study (BOSS)

World Journal of Surgery - Complications are common after ostomy surgery. Data from the Berlin OStomy Study were evaluated to determine risk factors for complications. Patients with a bowel ostomy...     

The impact of childhood sickness on adult socioeconomic outcomes: Evidence from late 19th century America

We use family fixed-effects models to estimate the impact of childhood health on adult literacy, labor force outcomes, and marital status among pairs of white brothers observed as children in the 1880 U.S. Census and then as adults in the 1900-1930 Censuses. Given our focus on the 19th century, we observed a wider array of infectious, chronic, and traumatic health problems than is observed using data that are more recent; our results thus provide some insights into circumstances in modern developing countries where similar health problems are more frequently observed. Compared to their healthy siblings, sick brothers were less likely to be located (and thus more likely to be dead) 20-50 years after their 1880 enumeration. Sick brothers were also less likely to be literate, to have ever been married, and to have reported an occupation. However, among those with occupations, sick and healthy brothers tended to do similar kinds of work. We discuss the implications of our results for research on the impact of childhood health on socioeconomic outcomes in developed and developing countries.     

Ueber Myopie und ihre Behandlung

Ohne Zusammenfassung     

Mechanical stretch induces clustering of beta1-integrins and facilitates adhesion

Human epithelial cells are permanently stimulated by external mechanical forces. The present in vitro study suggests that keratinocytes respond to mechanical strain by a coordinated spatial and functional utilization of beta1-integrins and the epidermal growth factor receptor (EGFR) with impact to the adhesion properties. It was found that a single mechanical stretch applied to HaCaT keratinocytes elevates the substrate adhesion, in particular to fibronectin and collagen type IV but not to laminin indicating the relevance of beta1-integrins in this process. This was confirmed using a functional blocking antibody directed against beta1-integrins which reversed the stretch-induced adhesion. Furthermore, mechanical stretch gives rise to a rapid redistribution of beta1-integrins in clusters on the basal cell membrane, without changing the overall amount of this particular integrin subset. Concomitantly, the EGFR co-localizes with beta1-integrin suggesting a functional cooperation of both membrane proteins in mechano-signaling. This is corroborated by data showing that stretch-induced activation of the EGFR and the downstream element extracellular regulated kinase 1/2 (ERK1/2) is reversed by preincubation with beta1-integrin antibodies. Vice versa, blocking the EGFR using a specific inhibitor abrogates stretch-induced ERK1/2 activation. In summary, these results show a functional cooperation of beta1-integrins and EGFR in the adhesion complex supporting the transmission of stretch-induced signals.