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Delaunay triangulation is an effective way to build a triangulation of a cloud of points, i.e., a partitioning of the points into simplices (triangles in 2D, tetrahedra in 3D, and so on), such that no two simplices overlap and every point in the set is a vertex of at least one simplex. Such a triangulation has been shown to have several interesting properties in terms of the structure of the simplices it constructs (e.g., maximising the minimum angle of the triangles in the bi-dimensional case) and has several critical applications in the contexts of computer graphics, computational geometry, mobile robotics or indoor localisation, to name a few application domains. This review paper revolves around three main pillars: (I) algorithms, (II) implementations over central processing units (CPUs), graphics processing units (GPUs), and field programmable gate arrays (FPGAs), and (III) applications. Specifically, the paper provides a comprehensive review of the main state-of-the-art algorithmic approaches to compute the Delaunay Triangulation. Subsequently, it delivers a critical review of implementations of Delaunay triangulation over CPUs, GPUs, and FPGAs. Finally, the paper covers a broad and multi-disciplinary range of possible applications of this technique.

Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

In this study, we have investigated the relationship between the plasma temperature in remote laser-induced breakdown spectroscopy (LIBS) experiments and the hydrophobic properties of silicone rubber insulators (SIRs). Contact angle and LIBS measurements were conducted on both artificially-aged (accelerated aging) and field-aged SIRs. This study reveals a clear connection between plasma temperature and the properties of aged SIRs on artificially-aged SIR specimens. Specifically, the plasma temperature exhibits a consistent increase with the duration of the accelerated aging test. The hydrophobicity of the artificially-aged SIRs was assessed by performing contact angle measurements, revealing a decrease in the hydrophobicity with increased aging test duration. Furthermore, we extended our investigation to the study of nine field-aged SIRs that had been in use on 150 kV overhead transmission lines for 0 to 21 years. We find that the laser absorption and hardness of the material do not relate to the plasma temperature. In summary, we observe a direct connection of plasma temperature to both contact-angle measurements and operation time of the in-service insulators. These results strongly suggest the potential use of LIBS for remotely evaluating the hydrophobicity and aging degree of silicone rubber insulators, thus assessing their real-time on-site operational quality.

Summary: Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19–2.25]), 26 months (1.20 [95% CI 0.48–1.91]), and 38 months (1.52 [95% CI 0.74–2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43–1.07]), 26 months (mean difference 0.65 [95% CI 0.27–1.03]), and 38 months (mean difference 0.72 [95% CI 0.25–1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34–43.38]), 26 months (mean difference 29.26 m [95% CI 14.87–43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32–54.09]). No new safety signals were identified. Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding: Financial support for the registry from Biogen, Novartis and Roche.

The essay examines the phenomenon of trolling in the context of politics and especially of international politics. Emphasis is given to how trolling functions within International Relations, particularly in respect to a conventional image of the field/discipline. Does it work in an affirmative or in a subversive manner? The usual analysis of trolls in instrumental terms, like ‘‘weapon’’, reinforces the impression that the aforementioned field and the respective theory, in their state-centric manifestation, hold up well. Trolls are used by states, often to strengthen the competitive spirit or regime survival. However, trolls may also be directed against states/regimes or the status quo and mainstream attitudes, at national and supranational levels. At its most extreme, the very understanding of trolling is possible to escape from the classics, namely a kind of aggressive behavior in social media. It further concerns a critical attitude towards certainties and knowledge claims. In short, trolling potentially poses challenges for the characteristics and evolution of politics as well as for the relationship between power and knowledge.

The Mediterranean diet is mostly based on high intakes of olive oil, vegetables, legumes, and fruits, with limited amounts of red meat and sweets, and is related to lower risk of cardiovascular diseases, mainly due to the health benefits of antioxidants of wild greens, fruits, and vegetables. Petromarula pinnata (L.) A. DC. is a unique (monotypic) and threatened local endemic wild edible green of Crete which is consumed raw in salads or cooked as an ingredient of the Mediterranean (Cretan) diet. In this study, we aimed to examine the nutritional value of P. pinnata with reference to wild-growing material; moreover, we investigated its chemical composition with 1H NMR spectra and its in vitro total phenolics and flavonoids (TPC, TF assays), and we evaluated the antioxidant (TAC, DPPH, and inhibition of lipid peroxidation), antimicrobial (MIC), and anti-inflammatory (inhibition of soybean lipoxygenase) in vitro activity during two different developmental stages (winter and summer collections), all referring to ex situ cultivated material (air-dried or frozen in liquid nitrogen). Our results showed that P. pinnata has good nutritional value, being rich in terpenoids and poor in phenolic compounds and flavonoids. Furthermore, the extracts showed high antioxidant activity for TAC and DPPH and some of the extracts had higher antioxidant activities than the standard compounds. The summer plant materials had higher antioxidant activity than the winter ones. The methanol/water extracts were the strongest inhibitors of the lipid peroxidation, and the methanol extracts were not found to be active. None of the extracts inhibited the soybean lipoxygenase, and thus they were devoid of anti-inflammatory activity. Finally, the extracts showed a moderate to strong bacterial inhibition. These findings consolidate that P. pinnata has a novel nutraceutical interest with high nutritional value and high antioxidant activity combined with bactericidal effect, thus updating the evaluation of its exploitation potential in the medicinal sector from below average (37%) to high (67%).

Chromophobe RCC (ChRCC) carries the best prognosis among all RCC subtypes, yet it lacks a proper grading system. Various systems have been suggested in the past, causing much controversy, and Avulova et al. recently proposed a promising four-tier grading system that takes into consideration tumor necrosis. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway plays a key role in ChRCC pathogenesis, highlighting its molecular complexity. The present retrospective study aimed to evaluate the prognostic factors associated with a more aggressive ChRCC phenotype. Materials and Methods: Seventy-two patients diagnosed with ChRCC between 2004 and 2017 were included in our study. Pathology reports and tissue blocks were reviewed, and immunohistochemistry (IHC) was performed in order to assess the expressions of CYLD (tumor-suppressor gene) and mTOR, among other markers. Univariate analysis was performed, and OS was assessed using the Kaplan–Meier method. Results: In our study, 74% of patients were male, with a mean age of 60 years, and the mean tumor size was 63 mm (±44). The majority (54%) were followed for more than 10 years at intervals ranging between 44 and 222 months. The risk of death was significantly higher for patients that were classified as Grade 4 in the Avulova system (HR: 5.83; 95% CI, 1.37–24.7; p: = 0.017). As far as the IHC is concerned, mTOR expression was associated with an HR of 8.57 (95% CI, 1.91–38.5; p = 0.005), and CYLD expression was associated with an HR of 17.3 (95% CI, 1.57–192; p = 0.02). Conclusions: In our study, the Avulova grading system seems to be positively correlated with OS in patients diagnosed with ChRCC. Furthermore, an elevated mTOR expression also shows a negative correlation with OS, whereas an elevated CYLD expression does not seem to exert a protective role. However, because only a small proportion (4.2%) of our patients died due to ChRCC, despite the long follow-up period, the results must be interpreted with caution. Further research is needed to validate our findings.

Background/ObjectiveNeurofilament light chain (NfL) has been proposed as a biomarker reflecting disease severity and therapy response in children with spinal muscular atrophy type 1 and 2 (SMA1 and 2). The objective of this study was to examine how serum NfL changes after gene replacement therapy (GRT) with onasemnogene abeparvovec-xioi.MethodsWe measured NfL in serum probes from 19 patients (10 SMA 1 and 6 SMA 2; 15 previously treated with nusinersen or risdiplam; 12 male) before and at variable time points after GRT. These values were related to motor scores (CHOP-Intend, HFMSE and RULM).ResultsMedian age at GRT was 19 months (range 2–46 months). Median NfL of all patients before GRT was 39 pg/ml (range 0–663 pg/ml; normal values

Scarcity of freshwater for agriculture has led to increased utilization of treated wastewater (TWW), establishing it as a significant and reliable source of irrigation water. However, years of research indicate that if not managed adequately, TWW may deleteriously affect soil functioning and plant productivity, and pose a hazard to human and environmental health. This review leverages the experience of researchers, stakeholders, and policymakers from Israel, the United-States, and Europe to present a holistic, multidisciplinary perspective on maximizing the benefits from municipal TWW use for irrigation. We specifically draw on the extensive knowledge gained in Israel, a world leader in agricultural TWW implementation. The first two sections of the work set the foundation for understanding current challenges involved with the use of TWW, detailing known and emerging agronomic and environmental issues (such as salinity and phytotoxicity) and public health risks (such as contaminants of emerging concern and pathogens). The work then presents solutions to address these challenges, including technological and agronomic management-based solutions as well as source control policies. The concluding section presents suggestions for the path forward, emphasizing the importance of improving links between research and policy, and better outreach to the public and agricultural practitioners. We use this platform as a call for action, to form a global harmonized data system that will centralize scientific findings on agronomic, environmental and public health effects of TWW irrigation. Insights from such global collaboration will help to mitigate risks, and facilitate more sustainable use of TWW for food production in the future.

Flow cytometry (FCM) is a widely used technique to study genome size (C-value), but recalcitrant metabolites in grapevines often hinder its efficiency in grapevine research. The aim of the present study was (i) to develop a novel buffer tailormade for the nuclei isolation of grapevines and (ii) to characterize a Cypriot germplasm collection based on C-values. A local cultivar “Xinisteri” was used as a pilot test to evaluate a Sorbitol-based buffer, while sprouting, young, and fully matured leaves were examined to evaluate the developmental parameter. The novel Sorbitol buffer was shown to have a coefficient of variation (CV) of 4.06%, indicating improved properties compared to other commonly used FCM buffers [WPB (7.69%), LB01 (6.69%), and LB (7.13%), respectively]. In addition, a significant variation in genome size between genotypes was found in a comprehensive application with 24 grape varieties. Nucleic content (2C) ranged from 0.577/1C pg for the “Assyrtiko” cultivar up to 0.597/1C pg for the “Spourtiko” cultivar, revealing a 17.6/1C Mbp difference. The lowest coefficient of variation (CV) across all entries was found in the variety “Ofthalmo” (2.29%), while the highest was observed in “Pinot Noir” (3.44%). Anova analysis revealed several distinct clusters, showing that in several cases, C-values can be used as a simple method to distinguish grapevine cultivars.

Abstract We explored the existence and application of standard operating procedures (SOPs) for pain management (PM) in German neonatal intensive care units (NICUs), and identified the factors associated with their application in practice. This study was part of the Safety4NICU project, a cross‐sectional survey conducted from 2015 to 2016. All 224 German NICUs were invited to participate, providing written consent from the head neonatologist and head nurse. We distributed questionnaires to the head neonatologist, the head nurse, and the NICU staff (physicians and nurses). We asked the head neonatologist whether written SOPs for PM existed, and we asked the staff whether these SOPs were applied in their daily routine. We received evaluable responses from 468 physicians and 1251 nurses from 76 NICUs. Of these 76 NICUs, the head neonatologists from 54 NICUs (71.1%) reported that written SOPs for PM exist. However, only 48.5% of the physicians and 53.7% of the nurses declared that these existing SOPs were also applied. We found various predictors for the existing SOPs as being applied, depending on the profession. For physicians, clinical training was important (OR: 2.482, p ≤ 0.05), while for nurses their working experience was a decisive predictor (OR: 1.265, p ≤ 0.05). For both, a high level of perceived cooperative norms between physicians and nurses increased the probability that SOPs for PM were applied, whereas a high bed turnover rate decreased that probability. According to the responses from head neonatologists, written SOPs for PM were common in German NICUs. However, if management strategies on pain existed, this did not mean that these were directly applied in the daily routine. Clinical training of the staff, the promotion of adequate interprofessional cooperation, as well as allowing time to deal with these SOPs might be all essential measures to strengthen the application.

Regular reporting of quality control is important in newborn hearing screening, ensuring early diagnosis and intervention. This study reports on a population-based newborn hearing screening program in North-Rhine, Germany and a hospital-based screening at a University Hospital for 2007–2016. The two-staged ‘screening’ and ‘follow-up’ program involving TEOAE and AABR recruited newborns through participating birth facilities. Results were sent to the regional tracking center, and the data were analyzed based on recommended benchmarks. The percentage of newborns from the participating birth facilities in the region increased from 1.4% in 2007 to 57.5% in 2016. The 10-year coverage rate for these newborns was 98.7%, the referral rate after a failed two-step screening was 3.4%, and the lost-to-follow-up rate was 1%. At the hospital, >95% of the screened newborns completed screening within 30 days, the 10-year referral rate was 5%, and 64% were referred within 3 months of age. The median time for screening completion was 6 days after birth, for referral it was 74 days after birth, and for diagnosis it was 55 days after birth. Regional–centralized tracking centers with uniform structure are necessary for proper quality control. Obligatory participation of birthing facilities and quality reports may improve performance, but the recommended quality criteria need considerable financial and infrastructural expenditure.