Novartis (Netherlands)

Urban sprawl poses a persistent challenge for stormwater management, as low-density development patterns increase impervious surfaces while limiting the effectiveness and affordability of conventional, centralised drainage infrastructure. Nature-based Solutions (NbS) for urban areas, such as rain gardens, bioswales, and bioretention areas, have demonstrated strong potential to address stormwater quantity and quality challenges while delivering co-benefits such as urban cooling, biodiversity enhancement, and recreational value. However, despite extensive piloting, NbS for stormwater services are insufficiently mainstreamed in many urban regions and grey infrastructure often remain the default. A key barrier lies in the difficulty of developing scalable business models and governance arrangements that enable their long-term provision as part of regular stormwater services, particularly in dispersed urban environments.This paper examines how co-creation processes can inform the development of business models for mainstreaming decentralised NbS for stormwater management in urban sprawl. Empirical insights are drawn from structured co-creation processes conducted in the metropolitan cities of Lyon (France) and Milan (Italy), involving the metropolitan authorities responsible for stormwater management, water utilities, planners, and researchers. The co-creation activities aimed to identify priority planning units or contexts, relevant stakeholder groups, and feasible implementation arrangements for NbS by aligning technical performance requirements with regional policies and governance structures, financing mechanisms, and stakeholder roles.Across both case studies, three distinct urban environments emerged as particularly relevant for NbS-based stormwater service delivery in urban sprawl: (i) single household units, (ii) parking lots, and (iii) public parks. These environments differ substantially in terms of land ownership, regulatory context, investment logic, and operation and maintenance responsibilities, resulting in divergent requirements for viable business models. Rather than proposing a one-size-fits-all solution, the paper demonstrates how each urban environment is associated with a specific set of business model logics and governance pathways.For single household units, mainstreaming NbS depends on incentive-based and technical assistance models that minimise transaction costs for private property owners and enable aggregation at neighbourhood scale. Parking lots, typically characterised by mixed ownership, offer opportunities for public–private partnership models that integrate NbS into asset management and redevelopment cycles. Public parks provide a setting for utility- or municipality-led models in which NbS are embedded into existing public service provision and justified through multi-functional value creation.The findings highlight the importance of distinguishing between urban environments as planning and business model units when seeking to mainstream NbS in urban contexts. Co-creation proved instrumental in revealing institutional opportunities and constraints, aligning actor expectations, and identifying realistic pathways from pilot projects to standard practice. The paper concludes that successful mainstreaming of NbS for decentralised stormwater management requires environment-specific business models supported by coherent governance arrangements. Consistently, focusing on specific urban environments significantly reduces the complexity of navigating urban governance systems and can accelerate the development of scalable business models for NbS.

Background. Adjuvant targeted therapy (ATT) with a combination of dabrafenib and trametinib after radical surgical treatment in patients with stage III skin melanoma (SM) with a BRAF V600 mutation reduces the risk of disease recurrence. The effectiveness of this approach has been demonstrated in randomized clinical trials, and also confirmed in several large non-Russian real-world (RW) studies. Aim. To evaluate, in RW settings, the effectiveness of ATT with a combination of dabrafenib and trametinib after definitive surgical treatment in patients with BRAF V600-positive SM in Russia. Materials and methods. The RATIONALE study is a prospective, non-interventional, multicenter RW study. The follow-up duration for the study was 1 year. Patients with SM older than 18 years who had previously started dabrafenib and trametinib therapy no more than 8 weeks prior to Visit 1 were included in the study. The paper presents results from the analysis of Cohort 1 only (patients who received dabrafenib and trametinib in the adjuvant setting). Results. The cohort included 214 patients with BRAF V600-mutated SM of stages IIIA–D and IV resectable. At the time of therapy initiation, the majority of patients were stage IIIc (54.7%) or IIIb (22.0%). The most common mutation – BRAF V600E – occurred in 66.3% of cases, while the second most common variant – BRAF V600 not otherwise specified – was detected in 31.3%. One-year overall survival for all included patients was 94%, one-year relapse-free survival was 84%, and one-year distant metastasis-free survival was 86%. No previously listed adverse events were reported. Adverse events led to therapy discontinuation in only 11.7% of cases. ATT did not reduce patients' quality of life. In the subgroup analysis, the effectiveness of the combination of dabrafenib and trametinib after removal of distant metastases (equivalent to stage IV resectable) was found, in particular, the one-year relapse-free survival rate was 83%, and the one-year overall survival rate was 100%, which is comparable to these indicators for stage IIIB-D (72–86 and 78–100%, respectively). Conclusion. The effectiveness and favorable safety profile of the combination of dabrafenib and trametinib in ATT after radical surgical treatment was confirmed in a population of Russian patients with SM in the RW settings.

The Mid-infrared ELT Imager and Spectrograph (METIS) is one of the scientific instruments for the ELT. The Common Fore Optics (CFO) is the first set of optics and mechanisms within the cryogenic instrument. A key element of the CFO is the Pupil Stabilization Mechanism (PSM), a tip/tilt mirror used for periodic adjustments of the pupil alignment during observations. The design challenges for the PSM involved achieving the required stability, resolution, and a sufficient stroke range/hold power while operating within the stringent requirements of the CFO. The design development lead to a monolithic design and integrated flexures driven by actuators with an integrated closed loop optical encoder.

The ALMA observatory in Chile is an interferometer consisting of 66 antennas that act together as a single telescope. Each antenna hosts a set of 10 receivers working in different frequency bands. The repetitive nature of ALMA demands a “serial” approach towards the development and production of its receivers. Series of up to 70 (66 and spares) high quality and reliable receivers are required, which can only be achieved when a special work attitude is adopted. All starts with a good design, considering that the receivers must be built in small series. Parts are ordered in industry, the design must be simple, structural wise, with as little as possible different parts. The receivers must be easy to build, accessible with dedicated tools and best is if assembly is possible with a single engineer only. In the ordering process contact on a regular basis is vital, not all information is transferable in drawings and documents. Working with wellknown companies is preferable. Inspection of components and parts needs the highest priority: for the assembly phase no checking or rework shall be needed. The engineer must be confident that all is perfect, just to be able to focus on the assembly only. Part of the inspection is the electronic and RF testing of different components. This beholds implementation of a good documenting system for these inspections: to be able to have close and fruitful contacts with the manufacturers, inspection reports are invaluable for a feedback loop to optimize the production of parts. Also, lessons learned in these documents from former projects shall be studied in advance of the start of the inspection or even the design phase. Conclusion is that to make reliable instruments in a repeatable way, hyperfocus is needed at the assembly process: the consequence is that all components on the workbench need to be in perfect condition; Product and Quality Assurance is the heart of this process.

The Dutch Rubin Enhanced Atmospheric Monitor – DREAM – brings high-resolution, real-time information on all-sky transparency and cloud coverage to the Vera C. Rubin Observatory. Leveraging the MASCARA legacy, DREAM employs five wide-field cameras, pointing upward and in the four cardinal directions. It precisely measures the brightness of all bright stars (V < 8.4) with a cadence of 6.4 seconds. To disentangle instrumental and stellar brightness variations from transmission fluctuations, a comprehensive spatial-temporal calibration is applied. The resulting transmission variations are calibrated and processed to generate an all-sky image of transparency, providing the actual cloud cover at an approximate cadence of 30 seconds. DREAM also produces calibrated light curves for stars brighter than magnitude 8.4, extending the temporal coverage of the MASCARA southern hemisphere survey. Integrated and tested at Leiden Observatory in 2023, DREAM was shipped in November of the same year and installed in close proximity to the Vera C. Rubin Observatory. In its initial phase, DREAM supplies cloud coverage and transparency data to the Auxiliary Telescope. Once the LSST Camera of the Vera C. Rubin Observatory becomes operational, DREAM will play a crucial role in optimizing the survey strategy by providing input to the scheduler, particularly in non-photometric conditions.

METIS, the Mid-infrared ELT Imager and Spectrograph for the Extremely Large Telescope (ELT), is one of the three firstgeneration science instruments, it has passed final design [1],[2] and is midway the Manufacturing, Assembly, Integration and verification (MAIV) phase. The Imager will be completely assembled and tested at MPIA in Heidelberg, Germany, before integration into the METIS instrument in Leiden, Netherlands. The Imager sub-system provides diffraction-limited imaging capabilities and low-resolution grism spectroscopy in two channels: the first covers the atmospheric L&M bands with a field of view of 11x11 arcsec, the second covers the N band, with a field of view of 14x14 arcsec. The two channels are equipped with a HAWAII-2RG detector for LM band and a GeoSnap detector for the N band, respectively [3],[5]. Challenging requirements suitable for high contrast imaging require a thorough integration and verification, particularly considering the size, complexity and the operating temperature of the instrument. Virtually, all components and units are in production or are already finished. The integration and verification of these units follow an MAIV plan including a detailed alignment scheme. The AIV part consists of three different phases: acceptance tests of components, alignment tasks, and verification of requirements. A dedicated test cryostat has been developed for the end-to-end verification to guarantee a smooth integration into the METIS instrument. Here, we present this MAIV process and describe in detail exemplary individual tasks of each phase to demonstrate the complexity of this stage of development and the managing of the challenging procedures. We also describe the tools and the corresponding setups used in the laboratory to execute the various tests, and the application of interferometric measurements at cryogenic conditions.

Lower systolic blood pressure (SBP) is known to be associated with poor prognosis in heart failure (HF). We evaluated the efficacy and safety of sacubitril/valsartan according to baseline SBP tertiles in Japanese patients from the PARALLEL-HF study. In all, 223 patients were stratified into tertiles according to baseline SBP (≤114 mmHg: n=75; >114 and ≤130 mmHg: n=76; and >130 mmHg: n=72). Patients with lower SBP (≤114 mmHg) had the highest median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations at baseline (P=0.0184). No significant difference was observed between sacubitril/valsartan and enalapril for the composite outcome of cardiovascular death and HF hospitalization across SBP tertiles (P-interaction=0.2682). Although the P-interaction value was not significant (0.2106), a greater reduction in NT-proBNP with sacubitril/valsartan compared with enalapril was observed in patients with SBP >130 mmHg (P=0.0076). The incidence of hypotension-related events and reduction or discontinuation of treatment due to hypotension-related events was higher in the lower SBP subgroup, and these events were more frequent in the sacubitril/valsartan than enalapril group. The efficacy of sacubitril/valsartan compared with enalapril was consistent across baseline SBP tertiles in Japanese patients from the PARALLEL-HF study. Hypotension-related events were more common in patients treated with sacubitril/valsartan with lower SBP.

The PARALLEL-HF study assessed the efficacy and safety of sacubitril/valsartan vs. enalapril in Japanese patients with chronic heart failure with reduced ejection fraction (HFrEF). This open-label extension (OLE) assessed long-term safety with sacubitril/valsartan. This study enrolled 150 patients who received sacubitril/valsartan 50 or 100 mg, b.i.d., in addition to optimal background heart failure (HF) therapy. A dose level of sacubitril/valsartan 200 mg, b.i.d., was targeted by Week 8. At OLE baseline, higher concentrations of B-type natriuretic peptide (BNP) and urine cGMP, and lower concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), were observed in the sacubitril/valsartan core group (patients who received sacubitril/valsartan in both the core and extension study) than in the enalapril core group (patients who received enalapril in the core study and were then transitioned to sacubitril/valsartan). The mean exposure to study drug was 98.9%. There was no trend of worsening of HF at Month 12. No obvious changes in cardiac biomarkers were observed, whereas BNP and urine cGMP increased and NT-proBNP decreased in the enalapril core group, which was evident at Weeks 2-4 and sustained to Month 12. Long-term sacubitril/valsartan at doses up to 200 mg, b.i.d., has a positive risk-benefit profile; it was safe and well tolerated in Japanese patients with chronic HFrEF.