To study the supramolecular polymerisation mechanisms of a self‐assembling system, concentration‐ and temperature‐dependent measurements can both be used to probe the transition from the molecular ...dissolved state to the aggregated state. In this report, both methods are evaluated to determine their effectiveness in identifying and quantifying the self‐assembly mechanism for isodesmic and cooperative self‐assembling systems. It was found that for a rapid and unambiguous determination of the self‐assembly mechanism and its thermodynamic parameters, temperature‐dependent measurements are more appropriate. These studies allow the acquisition of a large data set leading to an accurate determination of the self‐assembly mechanism and quantification of the different thermodynamic parameters that describe the supramolecular polymerisation. For a comprehensive characterisation, additional concentration‐dependent measurements can be performed.
Self‐assembly mechanisms of a self‐assembled system were studied by concentration‐ and temperature‐dependent measurements. Both methods were evaluated to determine their effectiveness in identifying and quantifying the self‐assembly mechanism for isodesmic and cooperative systems (see figure). For a fast and unambiguous determination of the assembly mechanism and its thermodynamic parameters, temperature‐dependent measurements are more appropriate.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and ...4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20).
Data from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways.
All FTC-OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome-wide monosomy (allelic state A) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state AB). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near-haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent).
We demonstrate that recurrent FTC-OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene dosage on especially chromosome 7 (containing EGFR, BRAF, cMET) is crucial for FTC-OV tumour survival is an important topic for future research. MICROARRAYS: Data are made available at GEO (GSE31828).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To determine the user experience of wearing comfort of reusable sterile surgical gowns and compare these gowns with conventional disposable surgical gowns.
Design
Cross‐sectional survey.
...Setting
An academic hospital in the Netherlands.
Population
Gynaecologists, surgeons, residents and operating room assistants (n=80).
Methods
Quantitative and qualitative data were obtained via a written questionnaire. Participants provided subjective comments and scored the reusable gown on each individual topic with a score from 1 to 5 (1 = unsatisfactory, 2 = moderate, 3 = good, 4 = very good, 5 = excellent) and compared the reusable gown with the conventional disposable alternative (better, equal or worse).
Main outcome measures
Wearing comfort: ventilation and temperature regulation, fit and length, functionality, barrier function and ease of use.
Results
The results of the overall scores of the reusable gown are scored as ‘very good’ (mean 4.3, SD ± 0.5) by its users. Regarding comparison of the gowns, more than 79% (lowest score 79%, highest score 95%) of the participants scored the reusable gown equal or higher on six of seven topics. The topic ‘ease of use’ was scored equal or higher by 59% of the participants. Subjective comments provided information on possible improvements.
Conclusions
The findings of this study demonstrate that there is professional acceptance regarding the utilisation of reusable surgical gowns. To facilitate broader adoption, it is imperative to foster collaboration among suppliers and healthcare institutions. The reusable surgical gown is an environmentally sustainable, safe and comfortable alternative in the operating room.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives
Radiocephalic arteriovenous fistulas (RCAVF) are the preferred vascular access (VA) for hemodialysis (HD). Cohort studies from North America revealed that nonmaturation is a significant ...disadvantage of RCAVFs compared to other VAs. DESIGN: This present retrospective study describes the incidence of nonmaturation of AVFs and functional failure of arteriovenous grafts (AVG) in a multicentre cohort in the Netherlands and attempts to create a prediction model for nonmaturation of RCAVFs. Furthermore, the efficacy of interventions to promote maturation as well as the variability between hemodialysis centers was evaluated.
Materials
Medical records from 8 hospitals from 1997 to 2016 were retrospectively evaluated for VA type, maturation/primary success and demographics and comorbidities.
Methods
A prediction model was created for RCAVF nonmaturation using multivariate logistic regression analysis, selecting significant predictors using backward selection. Discrimination and calibration of the model were assessed.
Results
1383 AVFs and 273 AVGs were included in 1221 patients. Overall nonmaturation was 24% for RCAVFs, and 11% for upper arm AVFs. The functional failure rate for AVGs was 6%. The nonmaturation rate of contralateral RCAVFs after failure of an RCAVF was 22%. Procedures to improve RCAVF maturation were successful in 98/142 cases (69%). Predictors for nonmaturation were female gender, peripheral vascular disease, cerebrovascular disease and a cephalic vein diameter <2.5 mm, but the prediction model lacked sensitivity and specificity predicting individual RCAVF nonmaturation (C-statistic 0.629).
Conclusion
Nonmaturation rates are highest for RCAVFs, but nonmaturation could not be predicted with demographic parameters.
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EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective
To assess the various factors that influence environmentally sustainable behaviour in gynaecological surgery and examine the differences between gynaecologists and residents.
Design
An ...interview study.
Setting
Academic and non‐academic hospitals in the Netherlands.
Population
Gynaecologists (n = 10) and residents (n = 6).
Methods
Thematic analysis of semi‐structured interviews to determine the various factors that influence environmentally sustainable behaviour in gynaecological surgery and to examine the differences between gynaecologists and residents. By using the Desmond framework and the COM‐B BCW, both organisational and individual factors related to behaviour were considered.
Main outcome measures
Factors that influence environmentally sustainable behaviour.
Results
Awareness is increasing but practical knowledge is insufficient. It is crucial to integrate education on the environmental impact of everyday decisions for residents and gynaecologists. Gynaecologists make their own choices but residents’ autonomy is limited. There is the necessity to provide environmentally sustainable surgical equipment without compromising other standards. There is a need for a societal change that encourages safe and open communication about environmental sustainability. To transition to environmentally sustainable practices, leadership, time, collaboration with the industry and supportive regulatory changes are essential.
Conclusion
This study lays the groundwork for promoting more environmentally sustainable behaviour in gynaecological surgery. The key recommendations, addressing hospital regulations, leadership, policy revisions, collaboration with the industry, guideline development and education, offer practical steps towards a more sustainable healthcare system. Encouraging environmentally sustainable practices should be embraced to enhance the well‐being of both our planet and our population, driving us closer to a more environmentally sustainable future in healthcare.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
To compare the carbon footprint of caesarean and vaginal birth.
Design
Life cycle assessment (LCA).
Setting
Tertiary maternity units and home births in the UK and the Netherlands.
...Population
Birthing women.
Methods
A cradle‐to‐grave LCA using openLCA software to model the carbon footprint of different modes of delivery in the UK and the Netherlands.
Main Outcome Measures
‘Carbon footprint’ (in kgCO2 equivalents kgCO2e).
Results
Excluding analgesia, the carbon footprint of a caesarean birth in the UK was 31.21 kgCO2e, compared with 12.47 kgCO2e for vaginal birth in hospital and 7.63 kgCO2e at home. In the Netherlands the carbon footprint of a caesarean was higher (32.96 kgCO2e), but lower for vaginal birth in hospital and home (10.74 and 6.27 kgCO2e, respectively). Emissions associated with analgesia for vaginal birth ranged from 0.08 kgCO2e (with opioid analgesia) to 237.33 kgCO2e (nitrous oxide with oxygen). Differences in analgesia use resulted in a lower average carbon footprint for vaginal birth in the Netherlands than the UK (11.64 versus 193.26 kgCO2e).
Conclusion
The carbon footprint of a caesarean is higher than for a vaginal birth if analgesia is excluded, but this is very sensitive to the analgesia used; use of nitrous oxide with oxygen multiplies the carbon footprint of vaginal birth 25‐fold. Alternative methods of pain relief or nitrous oxide destruction systems would lead to a substantial improvement in carbon footprint. Although clinical need and maternal choice are paramount, protocols should consider the environmental impact of different choices.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Fragile X syndrome is the most common monogenetic form of intellectual disability and autism. Although the Fmr1 knockout mouse model recapitulates many aspects of the human FXS condition, ...the establishment of robust social behavioural phenotypes suitable for drug screening has been difficult. Here, we describe a novel social behavioural paradigm, the Automated Tube Test (ATT), for which Fmr1 knockout mice demonstrate a highly reliable and robust phenotype. Fmr1 KO mice show highly dominant behaviour over wild-type littermates in the ATT. Consistent with previous findings, we observed a highly significant, albeit partial, rescue of the altered social behaviour of Fmr1 knockout mice in the ATT, using genetic (mGluR5 deletion) or pharmacological inhibition (mGluR5 antagonist) of mGluR5 signalling independently. Together, our results validate the Automated Tube Test as a robust outcome measure for social behaviour in preclinical research for FXS, and confirm the pathophysiological relevance of mGluR5 signalling. Moreover, our findings highlight the strategy of initiating pharmacological intervention in adulthood as holding significant clinical potential.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In relativistic heavy-ion collisions, anisotropic collective flow is driven, event by event, by the initial eccentricity of the matter created in the nuclear overlap zone. Interpretation of the ...anisotropic flow data thus requires a detailed understanding of the effective initial source eccentricity of the event sample. In this paper, we investigate various ways of defining this effective eccentricity using the Monte Carlo Glauber (MCG) approach. In particular, we examine the participant eccentricity, which quantifies the eccentricity of the initial source shape by the major axes of the ellipse formed by the interaction points of the participating nucleons. We show that reasonable variation of the density parameters in the Glauber calculation, as well as variations in how matter production is modeled, do not significantly modify the already established behavior of the participant eccentricity as a function of collision centrality. Focusing on event-by-event fluctuations and correlations of the distributions of participating nucleons, we demonstrate that, depending on the achieved event-plane resolution, fluctuations in the elliptic flow magnitude v{sub 2} lead to most measurements being sensitive to the root-mean-square rather than the mean of the v{sub 2} distribution. Neglecting correlations among participants, we derive analytical expressions for the participant eccentricity cumulants as a function of the number of participating nucleons, N{sub part}, keeping nonnegligible contributions up to O(1/N{sub part}{sup 3}). We find that the derived expressions yield the same results as obtained from mixed-event MCG calculations which remove the correlations stemming from the nuclear collision process. Most importantly, we conclude from the comparison with MCG calculations that the fourth-order participant eccentricity cumulant does not approach the spatial anisotropy obtained assuming a smooth nuclear matter distribution. In particular, for the Cu+Cu system, these quantities deviate from each other by almost a factor of 2 over a wide range in centrality. This deviation reflects the essential role of participant spatial correlations in the interaction of two nuclei.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM