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Zuyderland Hip Inference for Survival and Lifetime Expectancy (ZHISLE) following hip fracture surgery:validation of the model that demonstrated good predictive power
No full textPurpose: Proximal femoral fractures are common within the elderly population and are associated with a high risk of mortality and reduced quality of life. Hemiarthroplasty or osteosynthesis (extramedullary or intramedullary) is the primary treatment option for these fractures. However, within this fragile patient population many comorbidities, among others dementia, are seen. Therefore, predicting patients with a high mortality risk after surgery may lead to adopting alternative treatment options with less risks. This paper proposes a new model to distinguish patients with high postoperative mortality risk with adequate follow-up time in combination with a wide set of useful and available variables.Methods: Patients treated with hemiarthroplasty or osteosynthesis for proximal femoral fractures were studied, with a follow-up period of 6 months. Patients who died within this follow-up period were compared to survivors, and predicting variables were assessed in logistic regression: The Zuyderland Hip Inference for Survival and Lifetime Expectancy (ZHISLE). The model was validated internally against a held-out dataset. Furthermore, the model performance was compared against the Almelo Hip Fracture Score (AHFS) on the same sample.Results: Out of 2463 patients undergoing surgical treatment for proximal femoral fractures, 415 (16.8%) died within 183 days. Predictors for early mortality included old age, male sex, high heartbeat, KATZ-ADL and GFI scores, C-reactive protein and urea concentrations and low albumin concentration. Our model showed satisfactory predictive and discriminatory power (ROC curve = 0.81). Internal validation was good (ROC in validation dataset = 0.81), and better than the AHFS (ROC = 0.57).Conclusions: The ZHISLE model demonstrates good predictive power concerning mortality risk for old patients with a proximal femoral fracture. The model could benefit patients by indicating if a conservative, non-invasive policy might be a better option for those patients
HiFi long-read genomes for difficult-to-detect, clinically relevant variants
No full textClinical short-read exome and genome sequencing approaches have positively impacted diagnostic testing for rare diseases. Yet, technical limitations associated with short reads challenge their use for the detection of disease-associated variation in complex regions of the genome. Long-read sequencing (LRS) technologies may overcome these challenges, potentially qualifying as a first-tier test for all rare diseases. To test this hypothesis, we performed LRS (30× high-fidelity [HiFi] genomes) for 100 samples with 145 known clinically relevant germline variants that are challenging to detect using short-read sequencing and necessitate a broad range of complementary test modalities in diagnostic laboratories. We show that relevant variant callers readily re-identified the majority of variants (120/145, 83%), including ~90% of structural variants, SNVs/insertions or deletions (indels) in homologous sequences, and expansions of short tandem repeats. Another 10% (n = 14) was visually apparent in the data but not automatically detected. Our analyses also identified systematic challenges for the remaining 7% (n = 11) of variants, such as the detection of AG-rich repeat expansions. Titration analysis showed that 90% of all automatically called variants could also be identified using 15-fold coverage. Long-read genomes thus identified 93% of challenging pathogenic variants from our dataset. Even with reduced coverage, the vast majority of variants remained detectable, possibly enhancing cost-effective diagnostic implementation. Most importantly, we show the potential to use a single technology to accurately identify all types of clinically relevant variants
Thermal detection of Riboflavin in Almond Milk Using Molecularly Imprinted Polymers
No full textRiboflavin is an essential vitamin in our diet, mitigating many crucial cellular processes, while simultaneously being a powerful freshness indicator in food quality control. Given its significance, accurate riboflavin determination in complex food samples is indispensable and predominantly based on HPLC. A promising alternative are chemically stable molecularly imprinted polymers (MIPs), which are coupled to a low-cost thermal readout device to detect riboflavin in almond milk with minimal pretreatment steps. To this end, the MIP composition was optimized by fine-tuning the choice of monomer, crosslinker and solvent amount with the optimizations yielding a MIP with an IF of 2.61 and a maximal binding capacity of 8.34 mu mol/g. Subsequently, the optimized MIP was used as a functional recognition layer in the HTM setup and characterized by SEM and contact angle measurements. The sensor performance was assessed by loading assays with aqueous riboflavin solutions, selectivity studies with nutrients commonly found in almond milk and real-life applicability by determination of riboflavin in almond milk. The sensor exhibits a LOD of 3.1 mu M in almond milk and the riboflavin content can be determined with an accuracy of 98.6 %. These results highlight the sensor's straightforward capability of quantifying riboflavin in complex samples with minimal pretreatment
Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI:Part 2—Ex vivo imaging: Added value and acquisition
No full textThe value of preclinical diffusion MRI (dMRI) is substantial. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages including higher SNR and spatial resolution compared to in vivo studies, and enabling more advanced diffusion contrasts for improved microstructure and connectivity characterization. Another major advantage of ex vivo dMRI is the direct comparison with histological data, as a crucial methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work represents "Part 2" of a three-part series of recommendations and considerations for preclinical dMRI. We describe best practices for dMRI of ex vivo tissue, with a focus on the value that ex vivo imaging adds to the field of dMRI and considerations in ex vivo image acquisition. We first give general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in specimens and models and discuss why some may be more or less appropriate for different studies. We then give guidelines for ex vivo protocols, including tissue fixation, sample preparation, and MR scanning. In each section, we attempt to provide guidelines and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should lie. An overarching goal herein is to enhance the rigor and reproducibility of ex vivo dMRI acquisitions and analyses, and thereby advance biomedical knowledge
Newly diagnosed heart failure with reduced ejection fraction:timing, sequencing, and titration of guideline-recommended medical therapy
No full textBACKGROUND AND AIMS: Despite guidelines recommending rapid initiation and up-titration of Guideline-recommended medical therapy (GRMT) for heart failure (HF) with reduced ejection fraction (HFrEF), its feasibility in daily practice remains unclear. TITRATE-HF studies the feasibility of rapid GRMT implementation in de novo HFrEF patients, investigating titration patterns and identifying barriers to effective treatment. METHODS: This analysis focuses on the de novo HFrEF patients included in the TITRATE-HF study, an ongoing prospective HF registry conducted in 48 Dutch hospitals. A detailed logbook for each GRMT drug class was recorded, from diagnosis to six months, including initiations, dose adjustments, discontinuations, and reasons for changes. RESULTS: The study included 1508 de novo HFrEF patients (median age: 70 years [inter-quartile ranges, IQR 62-77]; 31% women; median left ventricular ejection fraction: 30% [IQR 25-35]). At 6 weeks, 46% of patients were using quadruple therapy. Within 6 weeks post-HFrEF diagnosis, 50% of patients were prescribed quadruple therapy at some point, with 84% remaining on it after 180 days. At 6 months, 66.3% of patients were prescribed quadruple therapy, but only 1.3% achieved target doses for all four drug classes. While side effects accounted for 20%-37% of cases where target doses were not reached, a large proportion was attributed to physicians accepting suboptimal doses. Drug titrations occurred frequently in the first 60 days after diagnosis, fading afterwards. Discontinuation rates for angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blocker, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors were 13%, 11%, 9%, 9%, 11%, and 9%, respectively, primarily due to side effects or intolerances. Rechallenging these drug classes was successful in over 83% of patients. CONCLUSIONS: The TITRATE-HF study demonstrates that rapid initiation of GRMT for HFrEF is feasible in real-world clinical practice. Nonetheless, our results highlight the urgency for a proactive approach and ongoing dose titration of pharmacological therapy beyond the initial first months to fully optimize treatment
The cohort effect in solar energy and nuclear power:unveiling collective agency in energy transitions
No full textHow does the collective agency of multiple individual actors shape energy transitions? This paper engages with the many, varying careers of petroleum chemists, engineers and (geo)physicists who got involved in the development of alternative energy sources during the second half of the Twentieth century. In this period alternatives to oil, such as nuclear and solar power, were developed, often with the aid of many actors with roots in the already established oil regime. To preserve the agency of these many individual actors within the broader framework of energy transitions offered by the Multi-Level Perspective (MLP), this paper argues for the inclusion of (generational) cohort theory from the social sciences. Using cohort theory helps us better understand the agency the multi-facetted careers of the studied (oil) actors, often leading them through the revolving door between the political landscape, the existing oil regime, and the new technological niches of solar and nuclear energy
Justice delayed? Dutch state and agency liability in historical cases of illegal intercountry adoption
No full textOn 19 April 2024, the Dutch Supreme Court rendered a ruling in the case of Dilani Butink, a Dutch adoptee from Sri Lanka who initiated legal proceedings against the adoption agency and the Dutch state. The latter, the plaintiff asserted, had failed to adequately investigate the legitimacy of her adoption in 1992 amidst widespread reports of abuses occurring in Sri Lanka during that period. She argued that this negligence had contributed to the ongoing uncertainty regarding her origins and the circumstances of her relinquishment for adoption. Claiming violations of her rights to identity and origin under the ECHR, the plaintiff demanded financial reparations from the two stakeholders. The Supreme Court's ruling in this case serves as a significant point of reference in the ongoing discourse on reparation in the aftermath of past illegal intercountry adoption, not only in the Netherlands but also in other European countries. This case note explores the complexities surrounding the questions regarding accountability of stakeholders in the receiving countries in cases of illegal intercountry adoptions
Participation in Victim-Offender Mediation Predicts Less Reoffending:A Propensity Score Matched Case-Control Study
No full textPrevious research on victim-offender mediation (VOM) and reoffending rates often lack valid control groups and might suffer from a self-selection bias. Moreover, VOM’s role in the criminal justice system, particularly the effect on sanctioning, has not been considered in explaining the lower reoffending rates. This research addressed these gaps, by comparing four offender groups and using propensity score matching (N=2,907): those who participated in VOM, those unwilling, those unable due to victim refusal, and those not referred. Results replicated that VOM participation predicts lower reoffending rates, primarily due to the mediation process itself rather than self-selection. While VOM reduced the likelihood of sanctions, this did not explain the observed decrease in reoffending rates