Electrochemistry of potential bioreductive alkylating quinones : Part 2. Electrochemical properties of 2,5-bis(1-aziridinyl)-3,6-bis(ethoxycarbonylamino)-1,4-benzoquinone and some model compounds

The reduction mechanism of 2,5-bis(1-aziridinyl)-3,6-bis(ethoxycarbonylamino)-1,4-benzoquinone (Diaziquone, AZQ) and several model compounds of the mono- and bis(1-aziridinyl)quinone type at the dropping mercury electrode in aqueous solutions was studied. In addition, the influence of methyl substitution of the aziridinyl moiety at the 2-position on the protonation of the aziridine nitrogen was investigated. Substituent effects on quinone reduction and aziridine protonation prior to and following quinone reduction were studied qualitatively

Electrochemistry of potentially bioreductive alkylating quinones : Part 1. Electrochemical properties of relatively simple quinones, as model compounds of mitomycin- and aziridinylquinone-type antitumour agents

The influence of methyl-, hydroxy and amino substituents on the electrochemical behaviour of simple 1,4-naphtho-and 1,4-benzoquinones, model compounds of many quinoid antitumour agents, in aqueous media was studied. Significant changes in electrochemical behaviour were observed, potentially the result of a change in the electron density of the quinone moiety, pre- or post-protonation of substituents, hydrogen bond formation, tautomerization reactions and steric interactions between the quinone moiety and substituents. The information obtained was of benefit in the elucidation of the reduction mechanisms of quinoid antitumour agents such as aziridnylquinones and mitomycins

Unscheduled return visits to a Dutch inner-city emergency department

Background Unscheduled return visits to the emergency department (ED) may reflect shortcomings in care. This study characterized ED return visits with respect to incidence, risk factors, reasons and post-ED disposition. We hypothesized that risk factors for unscheduled return and reasons for returning would differ from previous studies, due to differences in health care systems. Methods All unscheduled return visits occurring within 1 week and related to the initial ED visit were selected. Multivariable logistic regression was conducted to determine independent factors associated with unscheduled return, using patient information available at the initial visit. Reasons for returning unscheduled were categorized into illness-, patient- or physician-related. Post-ED disposition was compared between patients with unscheduled return visits and the patients who did not return. Results Five percent (n = 2,492) of total ED visits (n = 49,341) were unscheduled return visits. Patients with an urgent triage level, patients presenting during the night shift, with a wound or local infection, abdominal pain or urinary problems were more likely to return unscheduled. Reasons to revisit unscheduled were mostly illness-related (49%) or patient-related (41%). Admission rates for returning patients (16%) were the same as for the patients who did not return (17%). Conclusions Apart from abdominal complaints, risk factors for unscheduled return differ from previous studies. Short-term follow-up at the outpatient clinic or general practitioner for patients with urgent triage levels and suffering from wounds or local infections, abdominal pain or urinary problem might prevent unscheduled return

Treatments and costs for recurrent and/or metastatic squamous cell carcinoma of the head and neck in the Netherlands

__Abstract__ For patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), chemotherapy can prolong life and alleviate symptoms. However, expected gains may be small, not necessarily outweighing considerable toxicity and high costs. Treatment choice is to a large extent dependent on preferences of doctors and patients and data on these choices are scarce. The purpose of this study is to obtain real-world information on palliative systemic treatment and costs of R/M SCCHN in the Netherlands. In six Dutch head and neck treatment centers, data were collected on patient and tumor characteristics, treatment patterns, disease progression, survival, adverse events, and resource use for R/M SCCHN, between 2006 and 2013. 125 (14 %) out of 893 R/M SCCHN patients received palliative, non-trial first-line systemic treatment, mainly platinum + 5FU + cetuximab (32 %), other platinum-based combination therapy (13 %), methotrexate monotherapy (27 %) and capecitabine monotherapy (14 %). Median progression-free survival and overall survival were 3.4 and 6.0 months, respectively. 34 (27 %) patients experienced severe adverse events. Mean total hospital costs ranged from €10,075 (±€9,891) (methotrexate monotherapy) to €39,459 (±€21,149) (platinum + 5FU + cetuximab). Primary cost drivers were hospital stays and anticancer drug treatments. Major health care utilization and costs are involved in systemically treating R/M SCCHN patients with a limited survival

COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study

Background: 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. Methods: We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. Findings: Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. Interpretation: Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. Funding: EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health

Star clusters near and far; tracing star formation across cosmic time

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00690-x.Star clusters are fundamental units of stellar feedback and unique tracers of their host galactic properties. In this review, we will first focus on their constituents, i.e.\ detailed insight into their stellar populations and their surrounding ionised, warm, neutral, and molecular gas. We, then, move beyond the Local Group to review star cluster populations at various evolutionary stages, and in diverse galactic environmental conditions accessible in the local Universe. At high redshift, where conditions for cluster formation and evolution are more extreme, we are only able to observe the integrated light of a handful of objects that we believe will become globular clusters. We therefore discuss how numerical and analytical methods, informed by the observed properties of cluster populations in the local Universe, are used to develop sophisticated simulations potentially capable of disentangling the genetic map of galaxy formation and assembly that is carried by globular cluster populations.Peer reviewedFinal Accepted Versio