General practitioners' evaluations of optimal timing to initiate advance care planning for patients with cancer, organ failure, or multimorbidity: a health records survey study

Background: Appropriate timing to initiate advance care planning is difficult, especially for individuals with non-malignant disease in community settings. Aim: To identify the optimal moment for, and reasons to initiate advance care planning in different illness trajectories. Design and methods: A health records survey study; health records were presented to 83 GPs with request to indicate and substantiate what they considered optimal advance care planning timing within the 2 years before death. We used quantitative and qualitative analyses. Setting and patients: We selected and anonymized 90 health records of patients who died with cancer, organ failure or multimorbidity, from a regional primary care registration database in the Netherlands. Results: The median optimal advance care planning timing according to the GPs was 228 days before death (interquartile range 392). This moment was closer to death for cancer (87.5 days before death, IQR 302) than for organ failure (266 days before death, IQR 401) and multimorbidity (290 days before death, IQR 389) (p < 0.001). The most frequently mentioned reason for cancer was "receiving a diagnosis" (21.5%), for organ failure it was "after a period of illness" (14.7%), and for multimorbidity it was "age" and "patients" expressed wishes or reflections' (both 12.0%). Conclusion: The optimal advance care planning timing and reasons to initiate advance care planning indicated by GPs differ between patients with cancer and other illnesses, and they also differ between GPs. This suggests that "the" optimal timing for ACP should be seen as a "window of opportunity" for the different disease trajectories.Surgical oncolog

Microbial Maintenance: A Critical Review on Its Quantification

Microbial maintenance is an important concept in microbiology. Its quantification, however, is a subject of continuous debate, which seems to be caused by (1) its definition, which includes nongrowth components other than maintenance; (2) the existence of partly overlapping concepts; (3) the evolution of variables as constants; and (4) the neglect of cell death in microbial dynamics. The two historically most important parameters describing maintenance, the specific maintenance rate and the maintenance coefficient, are based on partly different nongrowth components. There is thus no constant relation between these parameters and previous equations on this subject are wrong. In addition, the partial overlap between these parameters does not allow the use of a simple combination of these parameters. This also applies for combinations of a threshold concentration with one of the other estimates of maintenance. Maintenance estimates should ideally explicitly describe each nongrowth component. A conceptual model is introduced that describes their relative importance and reconciles the various concepts and definitions. The sensitivity of maintenance on underlying components was analyzed and indicated that overall maintenance depends nonlinearly on relative death rates, relative growth rates, growth yield, and endogenous metabolism. This quantitative sensitivity analysis explains the felt need to develop growth-dependent adaptations of existing maintenance parameters, and indicates the importance of distinguishing the various nongrowth components. Future experiments should verify the sensitivity of maintenance components under cellular and environmental conditions

Aerobic nonylphenol degradation and nitro-nonylphenol formation by microbial cultures from sediments

Nonylphenol (NP) is an estrogenic pollutant which is widely present in the aquatic environment. Biodegradation of NP can reduce the toxicological risk. In this study, aerobic biodegradation of NP in river sediment was investigated. The sediment used for the microcosm experiments was aged polluted with NP. The biodegradation of NP in the sediment occurred within 8 days with a lag phase of 2 days at 30°C. During the biodegradation, nitro-nonylphenol metabolites were formed, which were further degraded to unknown compounds. The attached nitro-group originated from the ammonium in the medium. Five subsequent transfers were performed from original sediment and yielded a final stable population. In this NP-degrading culture, the microorganisms possibly involved in the biotransformation of NP to nitro-nonylphenol were related to ammonium-oxidizing bacteria. Besides the degradation of NP via nitro-nonylphenol, bacteria related to phenol-degrading species, which degrade phenol via ring cleavage, are abundantly present

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor

Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity. For sensing EGFR activity in cells, we used a genetically encoded CrkII-based biosensor which undergoes conformational changes upon tyrosine-221 phosphorylation by EGFR. We transfected this biosensor into EGFR-positive tumour cells using targeted lipopolyplexes bearing EGFR-binding peptides at their surfaces. In a murine model of basal-like breast cancer, we demonstrated a significant degree of intratumoral heterogeneity in EGFR activity, as well as the pharmacodynamic effect of a radionuclide-labeled EGFR inhibitor in situ. Furthermore, a significant correlation between high EGFR activity in tumour cells and macrophage-tumour cell proximity was found to in part account for the intratumoral heterogeneity in EGFR activity observed. The same effect of macrophage infiltrate on EGFR activation was also seen in a colorectal cancer xenograft. In contrast, a non-small cell lung cancer xenograft expressing a constitutively active EGFR conformational mutant exhibited macrophage proximity-independent EGFR activity. Our study validates the use of this methodology to monitor therapeutic response in terms of EGFR activity. In addition, we found iNOS gene induction in macrophages that are cultured in tumour cell-conditioned media as well as an iNOS activity-dependent increase in EGFR activity in tumour cells. These findings point towards an immune microenvironment-mediated regulation that gives rise to the observed intratumoral heterogeneity of EGFR signalling activity in tumour cells in vivo

Inequality: Developments in labour market and labour relations

The Dutch labour market and labour relations have experienced profound changes in recent years. This article discusses in particular the growing diversity, fragmentation and inequality in the labour market, as well as the mounting pressure on the representativeness of most of all trade unions, but also of employers’ organisations. The authors argue that these developments cannot be considered independently, especially where the shifting balance of power between unions and employers, the continuous wage moderation and the flexibilization of the labour market are concerned. The polder institutions are in a stalemate, the relationships between employers and unions at sectoral and national level are becoming more conflictive and the social partners are less and less able to reach consensus on the core social and economic subjects. These findings matter to the world of HRM in two ways. On the one hand, (the debate about) future HR-policies will be influenced strongly by the mentioned structural changes in the labour market and labour relations. On the other hand, these changes are the result of the choices made in HR strategies and HR practices in organisations. Keywords: labour relations, inequality, diversity, fragmentation, power balanc

Transvaginal hydrolaparoscopy and laparoscopy

Research Question: To evaluate the findings of outpatient transvaginal hydrolaparoscopy (THL) in comparison with diagnostic laparoscopy combined with chromopertubation in subfertile women. Design: In a retrospective study in four large teaching hospitals, all subfertile women who underwent a THL and a conventional laparoscopy as part of their fertility work-up in the period between 2000 and 2011 were studied. Findings at THL were compared with findings at diagnostic and therapeutic laparoscopies. Tubal occlusion, endometriosis and adhesions were defined as abnormalities. Results: Out of 1119 women, 1103 women underwent THL. A complete evaluation or incomplete but diagnostic procedure could be performed in 989 (89.7%) and 28 (2.5%), respectively. An incomplete non-diagnostic procedure was performed in 11 (1.0%) women. Failure of THL occurred in 75 women (6.8%) and 40 of these women (3.6%) subsequently underwent laparoscopy. Laparoscopy was performed in a total of 126 patients with a median time interval of 7 weeks (interquartile range [IQR] 3-13 weeks). Of 64 patients who successfully underwent both THL and laparoscopy, concordant findings were found in 53 women and discordant results in 11 women, 6 of which were caused by tubal spasm. Sensitivity of THL in detecting abnormalities was 100% and specificity was 22.2%, with a likelihood ratio of 1.29. Conclusion: THL in an outpatient setting can detect anatomical abnormalities comparable to the more invasive reference standard diagnostic laparoscopy. If THL succeeds, there is no need to add a diagnostic laparoscopy in the work-up.Rachel Tros, Mianna van Kessel, Jur Oosterhuis, Walter Kuchenbecker, Marlies Bongers, Ben Willem Mol, Carolien Kok