Probing efficient microbial CO2 utilisation through metabolic and process modelling.

Acetogenic gas fermentation is increasingly studied as a promising technology to upcycle carbon-rich waste gasses. Currently the product range is limited, and production yields, rates and titres for a number of interesting products do not allow for economically viable processes. By pairing process modelling and host-agnostic metabolic modelling, we compare fermentation conditions and various products to optimise the processes. The models were then used in a simulation of an industrial-scale bubble column reactor. We find that increased temperatures favour gas transfer rates, particularly for the valuable and limiting H2 , while furthermore predicting an optimal feed composition of 9:1 mol H2 to mol CO2 . Metabolically, the increased non-growth associated maintenance requirements of thermophiles favours the formation of catabolic products. To assess the expansion of the product portfolio beyond acetate, both a product volatility analysis and a metabolic pathway model were implemented. In-situ recovery of volatile products is shown to be within range for acetone but challenging due to the extensive evaporation of water, while the direct production of more valuable compounds by acetogens is metabolically unfavourable compared to acetate and ethanol. We discuss alternative approaches to overcome these challenges to utilise acetogenic CO2 fixation to produce a wider range of carbon negative chemicals.

Suicide by helium inhalation in the Netherlands between 2012 and 2019.

INTRODUCTION: In 2012 and 2013 a movie and a book about a 'dignified end of life' were published in the Netherlands. These items described suicide using an 'exit bag' to establish asphyxiation using helium (the helium method). 'Right-to-die-organisations' inform the elderly about this method. The purpose of this study is to investigate whether the use of suicidal asphyxiation by means of the helium method substituted other, related, methods following its publication in the Netherlands. MATERIAL AND METHODS: We analysed suicides in the Netherlands over the period from 1 July 2012 to 30 June 2019. We compared the number of deaths caused by the helium method with other, related, cases. Secondly, we related these deaths to the total number of inhabitants and suicides recorded by Statistics Netherlands. RESULTS: The study showed a stable trend in the use of the helium method in the period 2012-2019 and this was the same for the other, related methods. Individuals using the helium method were significantly younger than those using other, related, methods. At the scene of death, information about suicide and suicide notes were found more often at 'helium method' cases than with the 'other, related, methods' cases. Family was significantly more often present during a helium method suicide than during suicide by other, related, methods. DISCUSSION: The number of suicides by the helium method and other, related, cases is stable in the Netherlands over the past years. Therefore, we conclude that there is no substitution effect within this category of suicides. Whilst 'right-to-die-organisations' strive to inform the old and sick of the helium method, it is noteworthy that the individuals using the helium method are significantly younger than the individuals who choose other, related, methods.

Improving usual care after sudden death in the young with focus on inherited cardiac diseases (the CAREFUL study): a community-based intervention study.

AIMS: Inherited cardiac diseases play an important role in sudden death (SD) in the young. Autopsy and cardiogenetic evaluation of relatives of young SD victims identifies relatives at risk. We studied the usual care after SD in the young aimed at identifying inherited cardiac disease, and assessed the efficacy of two interventions to improve this usual care. METHODS AND RESULTS: We conducted a community-based intervention study to increase autopsy rates of young SD victims aged 1-44 years and referral of their relatives to cardiogenetic clinics. In the Amsterdam study region, a 24/7 central telephone number and a website were available to inform general practitioners and coroners. In the Utrecht study region, they were informed by a letter and educational meetings. In two control regions usual care was monitored. Autopsy was performed in 169 of 390 registered SD cases (43.3%). Cardiogenetic evaluation of relatives was indicated in 296 of 390 cases (75.9%), but only 25 of 296 families (8.4%) attended a cardiogenetics clinic. Autopsy rates were 38.7% in the Amsterdam study region, 45.5% in the Utrecht study region, and 49.0% in the control regions. The proportion of families evaluated at cardiogenetics clinics in the Amsterdam study region, the Utrecht study region, and the control regions was 7.3, 9.9, and 8.8%, respectively. CONCLUSIONS: The autopsy rate in young SD cases in the Netherlands is low and few families undergo cardiogenetic evaluation to detect inherited cardiac diseases. Two different interventions did not improve this suboptimal situation substantially.

Sudden death victims <45 years: Agreement between cause of death established by the forensic physician and autopsy results.

PURPOSE: The goal of this study was to ascertain accordance between cause of death established by the forensic physician and autopsy results in young sudden death victims in the Netherlands. METHODS: Sudden death victims aged 1-45 years examined by forensic physicians operating in the participating regions which also underwent an autopsy between January 2006 and December 2011 were included (n = 70). Cause of death established by the forensic physician based on the external medicolegal examination was compared with autopsy findings using the ICD10-classification. RESULTS: Autopsy findings revealed that the majority of sudden death victims have died from a cardiac disease (n = 51, 73%). Most of the presumed heart disease related cases were confirmed by autopsy (n = 13, 87%). On the contrary, a large number of deaths caused by circulatory diseases were not recognised by the forensic physician (n = 38, 75%). In most of these cases, the forensic physician was forced to report an undetermined cause due to the lack of a solid explanation for death. Cause of death reported by the forensic physician appeared to be in agreement with the autopsy results in 12 cases (17%). CONCLUSIONS: Cause of death determination in young sudden death victims is a difficult task for forensic physicians due to the limited tools available during the medicolegal examination. An effort should be made to standardize extensive post-mortem investigation after sudden death in the young. Autopsy can provide valuable information regarding the cause of death, which is of great importance in view of the identification of inheritable diseases among decedents and their families.

The pros and cons of intravitreal triamcinolone injections for uveitis and inflammatory cystoid macular edema.

Intravitreal triamcinolone acetonide (IVTA) injections are gaining in popularity and are regularly administered nowadays for various ocular diseases. This paper presents a literature review on the use, efficacy, and complications of IVTA application in non-infectious uveitis and inflammatory cystoid macular edema (CME). In addition, we describe the experiences of our own institute. IVTA applications brought about a quick improvement in vision in the majority of cases. Drawbacks included the temporary duration of the effect with the need for repeated injections which re-exposed patients to the risk of complications. The risk of bacterial endophthalmitis was 0.5% and was further influenced by the specific IVTA preparation. Based on the literature review, we chose ready-for-use IVTA injections prepared by our pharmacy department, in which 90% of the toxic additives were removed and the dispensed dose of triamcinolone acetonide was validated to diminish the risk of endophthalmitis. Elevated intraocular pressure (IOP) was seen in 30-43% of the eyes and cataract developed in 29% of the eyes of patients, who were usually of advanced age. In conclusion, the rapid effect of IVTA might be of value in severe presentations of non-infectious uveitis and CME and might shorten the time interval needed for the improvement.