Y-Parc (Switzerland)

There is currently limited data to guide treatment selection, dosing, combination strategies and sequencing in the management of myasthenia gravis (MG). Additionally, MG symptoms are heterogenous between people and with time, requiring an individualized treatment approach. As such, successful patient-physician communication is key. This Delphi project was undertaken by MG specialists and patient representatives to explore their opinion on improving MG management via effective physician-patient communication and collaboration approach. This mixed-methods study was conducted in two phases. In Phase I, seven MG specialists and two patient representatives contributed to idea generation. Relevant insights informed the development of the Phase II Delphi survey. A panel of 16 MG specialists and seven patient representatives participated in a two-round Delphi survey. Consensus was defined as ≥ 70% agreement or disagreement on a 6-point Likert scale. Participants responded to the survey from what they considered an ideal scenario, regardless of their real-world experience. Consensus was achieved on 89% of all statements. Key areas of alignment were – importance of incorporating patient preferences on quality of life (QoL), sustained symptom control, route of administration, and side effects profile. Both groups agreed that current clinical practices insufficiently integrate mental health considerations and patient engagement remains suboptimal. Two key areas of misalignment were – patient representative and physicians had different perspective on how well physicians understood patient preferences and both groups showed different interpretations of side effects (adverse reaction versus issues of tolerability). This Delphi consensus found that while physician and patient representatives shared similar perspectives these were not always reflected in current clinical practice due to differences in understanding of patient preferences. Prioritizing structured conversations on QoL, treatment expectations, and side effect were found important for physicians while improving access to information, openly communicating and actively participating in treatment decisions were key outcomes for patients. This study lays a valuable foundation for deepening conversations and alignment on key topics in MG management among the medical, patient and caregiving communities.

Chronic Kidney Disease Associated-Pruritus (CKD-aP) is frequent among hemodialysis patients. Its associations with hemodiafiltration or conventional hemodialysis and clinical characteristics are inconsistent in observational studies. This study aimed to assess the prevalence, severity and factors associated with CKD-aP among patients on hemodialysis in the French-speaking part of Switzerland, where hemodiafiltration is widely used. A cross-sectional design was used. Adults on hemodialysis for ≥ 6 months and free of cognitive impairment were recruited from 15 dialysis centers. A research nurse collected sociodemographic, clinical, laboratory data and assessed CKD-aP using the Visual Analogue Scale (VAS) and Verbal Rating Scale (VRS). A multilevel mixed-effects model with maximum likelihood estimation was performed to investigate associations. A total of 413 participants, mean age was 69.68 years (SD 13.52), were included; 66% were men, 73% on hemodiafiltration. CKD-aP prevalence was 25%. VAS average itch score of participants with CKD-aP was 4.74 ± 1.99, versus 6.62 ± 2.18 for the worst intensity itch. According to VRS, most participants with CKD-aP suffered moderate (61.4%) to severe (22%) itch within the past 24 h. Higher phosphorus levels were significantly associated with increased CKD-aP severity, but not prevalence. Depression, smoking, and polypharmacy were associated with increased CKD-aP severity, whereas hemodialysis modality, volume substitution, filter or access type were not. Despite high dialysis standards, CKD-aP remains a frequent symptom in Switzerland. Depression is associated with CKD-aP and its severity while hemodialysis modality is not. These results suggest that effective management of CKD-aP requires not only optimal dialysis prescription but also a holistic approach. Registered at ClinicalTrials.gov (NCT05524467) on 10.06.2022.

Reliable yield projections require both fruit counting and forecasting fruit size at harvest. The prediction of final fruit size primarily depends on established growth models, which rely mainly on isolated fruit growth measurements taken throughout the season. This study presents a novel predictive model for apple fruit growth based on past diameter measures and atmospheric pressure. The studied growth data was acquired within a season by continuously monitoring apple diameter using a connected fruit dendrometer. Preliminary analysis showed that atmospheric pressure also contributes to accurate diameter forecasting. Utilizing Long Short-Term Memory (LSTM) modeling, the proposed approach predicts fruit diameter over eight days based on past diameter and atmospheric pressure data collected over a week, achieving a Mean Absolute Error below 0.5 mm. Such a tool holds strong potential for optimizing harvest prediction and orchard management efficiency.

Impaired sleep is a global health concern. However, the environmental factors contributing to sleep impairment in urban settings are still not well understood. This study involved 179 participants from a Swiss municipality (Yverdon-les-Bains), where sleep quality and diurnal sleepiness were measured using validated questionnaires, alongside environmental and geo-referenced data. The findings revealed a high prevalence of sleep disorders across diverse demographic groups (respectively 15.6% for diurnal sleepiness and 91.1% for significantly altered sleep quality). Additionally, sleep disorders were associated with both environmental and socio-demographic factors. Geospatial analysis identified clusters of sleep disturbances in specific neighborhoods, with distinct associations to specific sub-scores (factors) of the sleep evaluation. Assessing sleep in urban environments is crucial, as it is linked to elevated levels of sleepiness. Environmental and socio-demographic variables play significant roles in these disturbances. The incorporation of geospatial analyses allows for a more precise identification of patterns within the city, offering opportunities for tailored interventions to address the different patterns of sleep disorders.

Laser powder bed fusion (LPBF) as an additive manufacturing (AM) technology has emerged as a powerful platform for producing multi-material metallic structures. The main drawbacks of using metallic powders for multi-material printing are related to technical issues (i.e. powder contamination reducing the reusability of the powder) and interfacial defects. This paper attempts to demonstrate the advantages of using a combination of metallic powders and thin foils for printing light titanium-aluminum multi-material structures. An AlSi12 powder was printed using the conventional LPBF process and the behavior of the second material feedstock was investigated using both Ti6Al4V powders and foils. The printing process was simulated numerically using a finite element model (FEM), and characterized experimentally through operando X-Ray diffraction (XRD). For the powder-powder combination, cracking near the interface between the two alloys was considered as a combined effect of residual stresses and the presence of brittle intermetallic compounds (IMCs); both were investigated using nanoindentation. Replacing the Ti6Al4V powder by a foil resulted in a thinner layer of Ti-Al IMCs near the interface, and eliminated the large interfacial cracks. The results from FEM and CALPHAD thermodynamic simulations, supported by operando XRD, indicated that the increased thermal conductivity of the foil, compared to powders, led to heat transfer within the foil and to the underlying LPBF structure, prior to local melting. The new thermal regime produced a flawless interface between Ti6Al4V and AlSi12, due to reduced residual stresses in the plane normal to the building direction, and lower volumes of brittle IMCs. It is concluded that using foils instead of powders mitigates cracking and enhances microstructures near the interface, due to changes in thermal regime and alloys mixing patterns.

BackgroundColorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC deaths can be reduced with prevention and early diagnosis. Circulating tumor DNA-based liquid biopsies, are emerging tools for cancer detection. However, the tumor-signal-dependent nature of this approach results in low sensitivity in precancerous and early CRC stages. Here we propose the host immune response to the onset of cancer as an alternative approach for early detection of CRC.MethodsWe perform whole transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from individuals with CRC, precancerous lesions or negative colonoscopy in two independent cohorts using next-generation sequencing.ResultsWe discover and validate novel early CRC RNA biomarkers. Taking into account, and adjusting for, the sensitivity of PBMCs transcriptomes to processing times, we report distinct transcriptomic changes in the periphery related to specific CRC stages. Activation of innate immunity is already detectable in the peripheral blood of individuals with pre-malignant advanced adenomas. This immune response is followed by signs of transient B-cell activation and sustained inhibition of T-cell responses along CRC progression, whereby at late stages, protumoral myeloid cells, wound healing and coagulation processes prevail. Moreover, some biomarkers show similar dysregulation in tumors and are implicated in known pathways of CRC pathophysiology.ConclusionsThe strong systemic immune modulation triggered during CRC progression leads to previously unnoticed alterations detectable in PBMCs, paving the way for the development of an early CRC screening blood test, incorporating 226 validated biomarkers identified through immunotranscriptomics.

Essential oils are secondary metabolites of aromatic plants and are used in phytotherapy to treat various diseases. In the present study, eight selected essential oils - ajwain oil (Trachyspermum ammi L.), fennel oil (Foeniculum vulgare Mill. subsp. vulgare var. vulgare), thyme oil chemotype (ct.) thymol (Thymus vulgaris L.), tea tree oil (Melaleuca alternifolia Cheel.), oregano oil (Origanum vulgare L.), mountain savory oil (Satureja montana L.), lemongrass oil (Cymbopogon citratus (DC.) Stapf.) and eucalyptus oil (Eucalyptus globulus Labill.) -were examined for their antibacterial effect against Pasteurella (P.) multocida and Mannheimia (M.) haemolytica isolates from deep nasopharyngeal swab samples of fattening calves using agar diffusion and microdilution. All eight essential oils were effective against the tested isolates. Lemongrass oil proved to be the most potent of all eight essential oils, while fennel oil was only weakly effective. Different antimicrobial effects were observed between the two research methods. The effectiveness of ajwain, thyme, oregano and mountain savory oils was comparable in agar diffusion. However, this could not be reproduced using the microdilution method. P. multocida was found to be more sensitive to all essential oils tested than M. haemolytica. This study shows that the tested essential oils have antimicrobial in-vitro effects on P. multocida and M. haemolytica isolates and that the examination method is associated with the test result.

Summary CO2 geological storage, where supercritical CO2 is injected into underground porous formations for long-term sequestration, is one of several mitigation strategies that have been proposed to control the level of CO2 in the atmosphere. CO2 can be injected into several formation types; deep saline aquifers are the most promising mainly because of their large storage capacity. However, safe and effective CO2 geological storage requires an understanding of the potential failure mechanisms that may lead to a loss of containment. In fact, injection of a fluid into an aquifer increases pore pressure above the initial value and this may trigger unwanted geomechanical effects such as fault reactivation or microseismicity. Additionally, the caprock overlaying the aquifer must be able to withstand the expected pressure increase without fracturing. While previous work has explored the mechanism underlying caprock tensile fracturing, an investigation was carried out to understand which parameters are more susceptible to trigger this mode of failure. This study presents comprehensive sensitivity analyses to highlight the relative contribution of different parameters to caprock tensile fracturing. A simple quasi-2D model comprising an aquifer, caprock and monitoring layer was first set up using the compositional reservoir simulator GEM. A total of 22 parameters among aquifer properties, caprock properties, simulation options and injection parameters were then selected as input variables, and simulations were run by varying one parameter at a time. The target variable was chosen as the maximum CO2 mass that could be injected before tensile fractures start opening in the caprock. Findings were then summarized in a tornado plot. For the range of values considered, the aquifer matrix permeability, caprock Young modulus and number of injection wells were found to have the highest impact on the target variable. Furthermore, results showed that higher quantities of stored CO2 can be achieved without caprock tensile failure in systems where the aquifer has a high Young modulus and Poisson ratio and the caprock has a low Young modulus and Poisson ratio. While this research focused on a simple model, these findings can help refine the current criteria for the selection of aquifers suitable for CO2 geological storage

Objective: This prospective study investigated the feasibility performing laparoscopic pelvic surgery in spinal anesthesia and analyzed their intraoperative side effects like pain and nausea and vomitus of 915 patients. Methods: Implementation and performance of laparoscopic surgery under local anes-thesia of 915 patients out of a total of 3212, who underwent laparoscopic pelvic surgery in spinal anesthesia, were analyzed in relation to BMI (Body Mass Index), obesity, pain during surgery and amount of intraperitoneal mmHg CO2 gas pressure and surgical complications. Results: BMI > 30, intraabdominal adhesions, increased duration of the operation, bleeding and increased intraperitoneal CO2 pressure were statistically significant as the main causes of pain during laparoscopic surgery in spinal anesthesia. Under-weight patients, on the other hand, had less pain when intra-abdominal pressure in-creased compared to those of normal weight. The appearance of pain, nausea and vomitus occurred in 10,3% and was easy to manage and treat. It did not affect the sur-geon's work and the course of the operation. Conclusion: In view of these observations, we are proposing spinal anesthesia for lap-aroscopic surgery as the first choice in those patients, who have no contraindications. In our knowledge this clinical study constitutes the largest clinical observations and dataset that applies spinal anesthesia in laparoscopic pelvic surgery.

With the increasing prevalence of neoplasia and kidney disease, patients undergoing oncological treatment are at greater risk of acute renal failure. Joint oncological and nephrological management requires a thorough understanding of the patient's clinical history, as well as the potential nephrotoxic effects of chemotherapy and immunotherapy. This article proposes a comprehensive approach to the assessment of acute renal failure in patients undergoing treatment for neoplasia.