Rational (Germany)

We report the development and application of a scalable machine learning (ML) framework (Minerva) for highly parallel multi-objective reaction optimisation with automated high-throughput experimentation (HTE). Minerva demonstrates robust performance with experimental data-derived benchmarks, efficiently handling large parallel batches, high-dimensional search spaces, reaction noise, and batch constraints present in real-world laboratories. Validating our approach experimentally, we apply Minerva in a 96-well HTE reaction optimisation campaign for a nickel-catalysed Suzuki reaction, tackling challenges in non-precious metal catalysis. Our approach effectively navigates the complex reaction landscape with unexpected chemical reactivity, outperforming traditional experimentalist-driven methods. Extending to industrial applications, we deploy Minerva in pharmaceutical process development, successfully optimising two active pharmaceutical ingredient (API) syntheses. For both a Ni-catalysed Suzuki coupling and a Pd-catalysed Buchwald-Hartwig reaction, our approach identifies multiple conditions achieving >95 area percent (AP) yield and selectivity, directly translating to improved process conditions at scale.

BackgroundThe development of a medical device requires strict adherence to regulatory processes. Prehabilitation in this context is a new area in surgery that trains, coaches, and advises patients in mental well-being, nutrition, and physical activity. As staff is permanently drained from clinical care, remote and digital solutions with real-time assessments of data, including patient-related outcome reporting, may simplify preparation before major surgeries.ObjectiveThis study aimed to evaluate the usability engineering process for the Prehab App, a newly developed medical device, in order to identify and adapt any design and usability flaws found.MethodsWe hypothesized that formative and summative usability testing would achieve 80% interrater and intrarater reliability and consistency and that the safety-relevant scenarios would uncover undetected risks of the medical device (stand-alone software class IIa). In total, 8 experts and 8 laypersons (patients and potential patients) were asked to evaluate paper-based mockups, followed by an evaluation of the minimal viable product (MVP) of the Prehab App at least more than 8 weeks later after instruction and training. The experts had to face 5 and the laypersons 6 usability scenarios. Their evaluations were measured with the Mobile App Rating Scale (MARS) and trustworthiness checklists (range 0-64, with higher scores indicating trustworthiness), and the usability scenarios were evaluated with the After Scenario Questionnaire (ASQ) and a judgment by an observer. The time taken for the scenarios was also recorded.ResultsMARS achieved constant scores of more than 4 out of 5 points for both experts and laypersons. The mean trustworthiness score was 51.3 (SD 2.7) for the experts and 50.8 (SD 2.1) for the laypersons (P=.68) in task I. The interrater correlation, shown by the Fleiss-Kappa value, was 0.87 (range 0.85-0.89) for all raters (N=16), 0.86 (range 0.82-0.91) for the experts (n=8, 50%), and 0.88 (range 0.84-0.93) for the laypersons (n=8, 50%), reflecting almost perfect agreement between the raters. This indicated the high quality of the usability. The usability scenarios were performed with ease, except for the onboarding part, when the wearable was required to be connected; this took a considerable amount of time and was recognized as a challenge to good usability.ConclusionsThe formative and summative evaluation of the Prehab App design resulted in good-to-acceptable results of the design and usability of the critical and safety-relevant areas of the medical device and stand-alone software. Usability testing improves medical devices early in the design and development process, reduces errors, and mitigates risks, and in this study, it delivered a profound ethical and medical justification for a randomized controlled trial (RCT) of the Prehab App in a remote setting as a next step in the development process.Trial RegistrationGerman Registry for Clinical Trials (DRKS00026985); https://drks.de/search/en/trial/DRKS00026985

Currently, there is an intensive discussion about enhancing and expanding outpatient rhinosurgical procedures. Many questions about how to stratify into out- and inpatient procedures are still not sufficiently clarified. Particularly, the use of nasal packing materials is not adequately discussed. We performed a Germany-wide survey among otorhinolaryngologists regarding the use of nasal packing materials in sinonasal surgery. Additionally, we asked for any complication in relation to nasal packing. In 85,6% nasal packing was used for septal and turbinate surgery at least occasionally, in 44,2% always. In sinus surgery these numbers are 94,1% and 49%, respectively. Non-resorbable nasal packing materials were predominantly used.Most frequent complications were bleeding with nasal packing in situ (> 50% of respondents) and posterior dislocation (24% of respondents), requiring emergency treatment. Death was listed in 5 patients. One patient suffered from permanent brain damage due to hypoxia. Application of non-resorbable nasal packing materials with occlusion of the nasal cavity carry a substantial risk of complications, which necessitate emergency treatment, thus requiring inpatient care.

Energy system modeling supports the identification of the optimal technology mix to achieve decarbonization targets across multiple sectors. Especially when sector coupling is considered for future technology landscapes, the large solution space leads to a complex optimization problem in terms of computational feasibility and data requirements. The authors identify a research gap in developing an open-source model structure with consideration of the relevant future technologies of power, heat, other conversions, transport, and industry defined with a new level of detail in a sector-coupled energy world and in including detailed insights into the accompanying definition process. A strong focus is set on the transparency and reproducibility of the provided open-source structure and its flexible and consistent application to different framework families to foster the ease of applicability of this work. The paper first gives a detailed description of the model base, including an overview of the model frame definition process, the core adjustments to model sector coupling appropriately, and the measures to make the resulting problem computationally feasible. The core result of this work is the presentation of a detailed model structure to model sector coupling for a German energy system, yielding approximately 2000 processes that characterize the heterogeneous and technology-open landscape of existing and possible future technologies across relevant energy sectors. This supports energy system modelers in understanding and reproducing energy system models based on open-source data and thereby tries to accelerate the research on sector coupling and its role in the energy transition.

Prehabilitation is a multimodal concept to improve functional capability prior to surgery, so that the patients' resilience is strengthened to withstand any peri- and postoperative comorbidity. It covers physical activities, nutrition, and psychosocial wellbeing. The literature is heterogeneous in outcomes and definitions. In this scoping review, class 1 and 2 evidence was included to identify seven main aspects of prehabilitation for the treatment pathway: (i) risk assessment, (ii) FITT (frequency, interventions, time, type of exercise) principles of prehabilitation exercise, (iii) outcome measures, (iv) nutrition, (v) patient blood management, (vi) mental wellbeing, and (vii) economic potential. Recommendations include the risk of tumor progression due to delay of surgery. Patients undergoing prehabilitation should perceive risk assessment by structured, quantifiable, and validated tools like Risk Analysis Index, Charlson Comorbidity Index (CCI), American Society of Anesthesiology Score, or Eastern Co-operative Oncology Group scoring. Assessments should be repeated to quantify its effects. The most common types of exercise include breathing exercises and moderate- to high-intensity interval protocols. The program should have a duration of 3-6 weeks with 3-4 exercises per week that take 30-60 min. The 6-Minute Walking Testing is a valid and resource-saving tool to assess changes in aerobic capacity. Long-term assessment should include standardized outcome measurements (overall survival, 90-day survival, Dindo-Clavien/CCI®) to monitor the potential of up to 50% less morbidity. Finally, individual cost-revenue assessment can help assess health economics, confirming the hypothetic saving of $8 for treatment for $1 spent for prehabilitation. These recommendations should serve as a toolbox to generate hypotheses, discussion, and systematic approaches to develop clinical prehabilitation standards.