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Liquid streets: early modern waterways in urban spaces
No full textThe image of urban canals is readily associated today with specific cities, such as Venice, Amsterdam, or Recife; in the early modern period, however, waterways were a commonplace feature of most urban landscapes. Focusing on Augsburg, Florence, and the Dutch Republic as examples, this article will compare urban highways and waterways. Similarities will be identified between their function, their location, and their administration. These similarities, together with a brief discussion of etymology, make «liquid streets» an interesting label with which to think about urban rivers and canals. This article will also show, however, that there was more than similarities to the comparison of highways and waterways: in early modern cities, rivers and canals often went beyond streets and roads in function, location, and administration
Using high-density SNP data to unravel the origin of the Franches-Montagnes horse breed.
Get PDFBACKGROUND
The Franches-Montagnes (FM) is the last native horse breed of Switzerland, established at the end of the 19th century by cross-breeding local mares with Anglo-Norman stallions. We collected high-density SNP genotype data (Axiom™ 670 K Equine genotyping array) from 522 FM horses, including 44 old-type horses (OF), 514 European Warmblood horses (WB) from Sweden and Switzerland (including a stallion used for cross-breeding in 1990), 136 purebred Arabians (AR), 32 Shagya Arabians (SA), and 64 Thoroughbred (TB) horses, as introgressed WB stallions showed TB origin in their pedigrees. The aim of the study was to ascertain fine-scale population structures of the FM breed, including estimation of individual admixture levels and genomic inbreeding (FROH) by means of Runs of Homozygosity.
RESULTS
To assess fine-scale population structures within the FM breed, we applied a three-step approach, which combined admixture, genetic contribution, and FROH of individuals into a high-resolution network visualization. Based on this approach, we were able to demonstrate that population substructures, as detected by model-based clustering, can be either associated with a different genetic origin or with the progeny of most influential sires. Within the FM breed, admixed horses explained most of the genetic variance of the current breeding population, while OF horses only accounted for a small proportion of the variance. Furthermore, we illustrated that FM horses showed high TB admixture levels and we identified inconsistencies in the origin of FM horses descending from the Arabian stallion Doktryner. With the exception of WB, FM horses were less inbred compared to the other breeds. However, the relatively few but long ROH segments suggested diversity loss in both FM subpopulations. Genes located in FM- and OF-specific ROH islands had known functions involved in conformation and behaviour, two traits that are highly valued by breeders.
CONCLUSIONS
The FM remains the last native Swiss breed, clearly distinguishable from other historically introgressed breeds, but it suffered bottlenecks due to intensive selection of stallions, restrictive mating choices based on arbitrary definitions of pure breeding, and selection of rare coat colours. To preserve the genetic diversity of FM horses, future conservation managements strategies should involve a well-balanced selection of stallions (e.g., by integrating OF stallions in the FM breeding population) and avoid selection for rare coat colours
Composition and sources of carbonaceous aerosol in the European Arctic at Zeppelin Observatory, Svalbard (2017 to 2020)
Get PDFWe analyzed long-term measurements of organic carbon, elemental carbon, and source-specific organic tracers from 2017 to 2020 to constrain carbonaceous aerosol sources in the rapidly changing Arctic. Additionally, we used absorption photometer (Aethalometer) measurements to constrain equivalent black carbon (eBC) from biomass burning and fossil fuel combustion, using positive matrix factorization (PMF).
Our analysis shows that organic tracers are essential for understanding Arctic carbonaceous aerosol sources. Throughout 2017 to 2020, levoglucosan exhibited bimodal seasonality, reflecting emissions from residential wood combustion (RWC) in the heating season (November to May) and from wildfires (WFs) in the non-heating season (June to October), demonstrating a pronounced interannual variability in the influence of WF. Biogenic secondary organic aerosol (BSOA) species (2-methyltetrols) from isoprene oxidation was only present in the non-heating season, peaking in July to August. Warm air masses from Siberia led to a substantial increase in 2-methyltetrols in 2019 and 2020 compared to 2017 to 2018. This highlights the need to investigate the contribution of local sources vs. long-range atmospheric transport (LRT), considering the temperature sensitivity of biogenic volatile organic compound emissions from Arctic vegetation. Tracers of primary biological aerosol particles (PBAPs), including various sugars and sugar alcohols, showed elevated levels in the non-heating season, although with different seasonal trends, whereas cellulose had no apparent seasonality. Most PBAP tracers and 2-methyltetrols peaked during influence of WF emissions, highlighting the importance of measuring a range of source-specific tracers to understand sources and dynamics of carbonaceous aerosol. The seasonality of carbonaceous aerosol was strongly influenced by LRT episodes, as background levels are extremely low. In the non-heating season, the organic aerosol peak was as influenced by LRT, as was elemental carbon during the Arctic haze period.
Source apportionment of carbonaceous aerosol by Latin hypercube sampling showed mixed contributions from RWC (46 %), fossil fuel (FF) sources (27 %), and BSOA (25 %) in the heating season. In contrast, the non-heating season was dominated by BSOA (56 %), with lower contributions from WF (26 %) and FF sources
(15 %).
Source apportionment of eBC by PMF showed that FF combustion dominated eBC (70±2.7 %), whereas RWC (22±2.7 %) was more abundant than WF (8.0±2.9 %). Modeled BC concentrations from FLEXPART (FLEXible PARTicle dispersion model) attributed an almost equal share to FF sources (51±3.1 %) and to biomass
burning. Both FLEXPART and the PMF analysis concluded that RWC is a more important source of (e)BC than WF. However, with a modeled RWC contribution of 30±4.1% and WF of 19±2.8 %, FLEXPART suggests relatively higher contributions to eBC from these sources. Notably, the BB fraction of EC was twice as high as
that of eBC, reflecting methodological differences between source apportionment by LHS and PMF. However, important conclusions drawn are unaffected, as both methods indicate the presence of RWC- and WF-sourced BC at Zeppelin, with a higher relative BB contribution during the non-heating season.
In summary, organic aerosol (281±106 ng
Depth distortion and angular deviation of a fully guided tooth-supported static surgical guide in a partially edentulous patient: A systematic review and meta-analysis.
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This systematic review and meta-analysis aimed to evaluate the depth distortion and angular deviation of fully-guided tooth-supported static surgical guides (FTSG) in partially edentulous arches compared to partially guided surgical guides or freehand.
MATERIAL AND METHODS
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the Open Science Framework (OSF). The formulated population, intervention, comparison, and outcome (PICO) question was: "In partially edentulous arches, what are the depth distortion and angular deviation of FTSG compared to partially guided surgical guides or freehand?" The search strategy involved four main electronic databases, and an additional manual search was completed in November 2023 by following an established search strategy. Initial inclusion was based on titles and abstracts, followed by a detailed review of selected studies, and clinical studies that evaluated the angular deviations or depth distortion in FTSG in partial arches, compared to partially guided surgical guides or freehand, were included. In FTSG, two surgical approaches were compared: open flap and flapless techniques, and two digital methods were assessed for surgical guide design with fiducial markers or dental surfaces. A qualitative analysis for clinical studies was used to assess the risk of bias. The certainty of the evidence was assessed according to the grading of recommendations, assessment, development, and evaluations (GRADE) system. In addition, a single-arm meta-analysis of proportion was performed to evaluate the angular deviation of freehand and FTSG.
RESULTS
Ten studies, published between 2018 and 2023, met the eligibility criteria. Among them, 10 studies reported angular deviations ranging from -0.32° to 4.96° for FTSG. Regarding FTSG surgical approaches, seven studies examined the open flap technique for FTSG, reporting mean angular deviations ranging from 2.03° to 4.23°, and four studies evaluated flapless FTSG, reporting angular deviations ranging from -0.32° to 3.38°. Six studies assessed the freehand surgical approach, reporting angular deviations ranging from 1.40° to 7.36°. The mean depth distortion ranged between 0.19 mm to 2.05 mm for open flap FTSG, and between 0.15 mm to 0.45 mm for flapless FTSG. For partially guided surgical guides, two studies reported angular deviations ranging from 0.59° to 3.44°. Seven studies were eligible for meta-analysis, focusing on the FTSG in open flap technique, with high heterogeneity (I2 (95%CI) = 92.3% (88.7%-96.4%)). In contrast, heterogeneity was low in studies comparing freehand versus FTSG in open flap techniques (I2 (95%CI) = 21.3% (0.0%-67.8%)), favoring the FTSG surgical approach.
CONCLUSION
In partially edentulous arches, FTSG systems exhibited less angular deviation than freehand and partially guided surgical guides. Flapless surgical approaches were associated with reduced angular deviation and depth distortion, suggesting a potential preference for the FTSG method in these procedures
The molecular basis of tRNA selectivity by human pseudouridine synthase 3.
No full textPseudouridine (Ψ), the isomer of uridine, is ubiquitously found in RNA, including tRNA, rRNA, and mRNA. Human pseudouridine synthase 3 (PUS3) catalyzes pseudouridylation of position 38/39 in tRNAs. However, the molecular mechanisms by which it recognizes its RNA targets and achieves site specificity remain elusive. Here, we determine single-particle cryo-EM structures of PUS3 in its apo form and bound to three tRNAs, showing how the symmetric PUS3 homodimer recognizes tRNAs and positions the target uridine next to its active site. Structure-guided and patient-derived mutations validate our structural findings in complementary biochemical assays. Furthermore, we deleted PUS1 and PUS3 in HEK293 cells and mapped transcriptome-wide Ψ sites by Pseudo-seq. Although PUS1-dependent sites were detectable in tRNA and mRNA, we found no evidence that human PUS3 modifies mRNAs. Our work provides the molecular basis for PUS3-mediated tRNA modification in humans and explains how its tRNA modification activity is linked to intellectual disabilities
Minibeam Radiation Therapy Treatment (MBRT): Commissioning and First Clinical Implementation.
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Minibeam radiation therapy (MBRT) is characterized by the delivery of submillimeter wide regions of high "peak" and low "valley" doses throughout a tumor. Preclinical studies have long shown the promise of this technique, and we report here the first clinical implementation of MBRT.
METHODS
A clinical orthovoltage unit was commissioned for MBRT patient treatments using 3, 4, 5, 8, and 10 cm diameter cones. The 180 kVp output was spatially separated into minibeams using a tungsten collimator with 0.5 mm wide slits spaced 1.1 mm on center. Percentage depth dose (PDD) measurements were obtained using film dosimetry and plastic water for both peak and valley doses. PDDs were measured on central axis for offsets of 0, 0.5, and 1 cm. The peak-to-valley ratio (PVR) was calculated at each depth for all cones and offsets. To mitigate the effects of patient motion on delivered dose, patient-specific 3D printed collimator holders were created. These conformed to the unique anatomy of each patient and affixed the tungsten collimator directly to the body. Two patients were treated with MBRT, both received 2 fractions.
RESULTS
Peak PDDs decreased gradually with depth. Valley PDDs initially increased slightly with depth, then decreased gradually beyond 2 cm. PVRs were highest at the surface for smaller cone sizes and offsets. In vivo film dosimetry confirmed a distinct delineation of peak and valley doses on both patients treated with MBRT with no dose blurring. Both patients experienced prompt improvement in symptoms and tumor response.
CONCLUSIONS
We report commissioning results, treatment processes, and the first two patients treated with MBRT using a clinical orthovoltage unit. While demonstrating feasibility of this approach is a crucial first step toward wider translation, clinical trials are needed to further establish safety and efficacy
Comparison of the dosimetry of scandium-43 and scandium-44 patient organ doses in relation to commonly used gallium-68 for imaging neuroendocrine tumours.
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Several research groups have explored the potential of scandium radionuclides for theragnostic applications due to their longer half-lives and equal or similar coordination chemistry between their diagnostic and therapeutic counterparts, as well as lutetium-177 and terbium-161, respectively. Unlike the gallium-68/lutetium-177 pair, which may show different in-vivo uptake patterns, the use of scandium radioisotopes promises consistent behaviour between diagnostic and therapeutic radiopeptides. An advantage of scandium's longer half-life over gallium-68 is the ability to study radiopeptide uptake over extended periods and its suitability for centralized production and distribution. However, concerns arise from scandium-44's decay characteristics and scandium-43's high production costs. This study aimed to evaluate the dosimetric implications of using scandium radioisotopes with somatostatin analogues against gallium-68 for PET imaging of neuroendocrine tumours.
METHODS
Absorbed dose per injected activity (AD/IA) from the generated time-integrated activity curve (TIAC) were estimated using the radiopeptides [43/44/44mSc]Sc- and [68Ga]Ga-DOTATATE. The kidneys, liver, spleen, and red bone marrow (RBM) were selected for dose estimation studies. The EGSnrc and MCNP6.1 Monte Carlo (MC) codes were used with female (AF) and male (AM) ICRP phantoms. The results were compared to Olinda/EXM software, and the effective dose concentrations assessed, varying composition between the scandium radioisotopes.
RESULTS
Our findings showed good agreement between the MC codes, with - 3 ± 8% mean difference. Kidneys, liver, and spleen showed differences between the MC codes (min and max) in a range of - 4% to 8%. This was observed for both phantoms for all radiopeptides used in the study. Compared to Olinda/EXM the largest observed difference was for the RBM, of 21% for the AF and 16% for the AM for scandium- and gallium-based radiopeptides. Despite the differences, our findings showed a higher absorbed dose on [43/44Sc]Sc-DOTATATE compared to its 68Ga-based counterpart.
CONCLUSION
This study found that [43/44Sc]Sc-DOTATATE delivers a higher absorbed dose to organs at risk compared to [68Ga]Ga-DOTATATE, assuming equal distribution. This is due to the longer half-life of scandium radioisotopes compared to gallium-68. However, calculated doses are within acceptable ranges, making scandium radioisotopes a feasible replacement for gallium-68 in PET imaging, potentially offering enhanced diagnostic potential with later timepoint imaging
Multidimensional trait space outlines the effects of changes in abiotic filtering on aquatic plant community from sub-Antarctic ponds
Get PDFIn the current context of climate changes, which causes strong habitat variation, an understanding of the mechanisms underlying plant community dynamics is crucial to predict species fates. The taking of inter- and intraspecific trait variability into account would aid the identification of these mechanisms. Recently, a method involving the calculation of hypervolumes (n-dimensional spaces of trait values) was developed for the study of plant responses to their environments. Through hypervolume comparison, we examined the effects of interannual variations in abiotic conditions on aquatic plant communities in ponds of the sub-Antarctic Iles Kerguelen. This model system is particularly relevant for the examination of the consequences of climate changes-related habitat variation, as aquatic plant communities are adapted to cold and overall stable habitat conditions and the sub-Antarctic climate is changing rapidly. We conducted field sampling over four years at three sites. For all aquatic species, we measured five foliar, shoot, and clonal traits characterizing individual growth strategies that are likely to respond to variations in abiotic conditions on 1565 ramets over the four years. We measured 10 abiotic variables to characterize the plants' habitats every three months during the survey period. Hypervolumes were calculated for each site and year to assess variation in aquatic plant strategies at the community level. We demonstrated (i) the importance of spatiotemporal gradients of trophic status, temperature, and pH and dissolved oxygen concentration for the functional structure of aquatic plant communities; (ii) that the shape of the mean response was trait dependent, with traits related to plant metabolism (specific leaf area and specific internode mass) and three-dimensional space exploration (height and internode length) responding to the three spatiotemporal abiotic gradients; (iii) that selection pressures were especially high on aerial traits relative to clonal traits; and (iv) that given the community response to interannual variations of abiotic conditions, environmental changes should impact macrophyte community productivity. Synthesis. We conclude that the examination of interannual abiotic variation over four years is sufficient to detect rapid responses of macrophyte communities, with likely reliance on phenotypic plasticity. Our findings may inform the characterization of future functional changes in aquatic plant communities of the sub-Antarctic region, where similar species are found
Teaching team competencies within resuscitation training: A systematic review.
Get PDFOBJECTIVES
To evaluate the effectiveness of life support training with specific emphasis on team competencies on clinical and educational outcomes.
METHODS
This systematic review was prospectively registered (PROSPERO CRD42023473154) and followed the PICOST (population, intervention, comparison, outcome, study design, timeframe) format. All randomized controlled trials and non-randomized studies evaluating learners undertaking life support training with specific emphasis on team competencies in any setting (actual and simulated resuscitations) were included. Unpublished studies were excluded. Medline, Embase and Cochrane databases as well as trial registries were searched from inception to August 2023 (updated January 18, 2024). Two researchers performed title and abstract screening, full-text screening, data extraction, assessment of risk of bias (using RoB2 and ROBINS-I) and certainty of evidence (using GRADE). PRISMA reporting checklist was used to report the results. No funding was obtained to perform this systematic review.
RESULTS
The literature search identified 5470 manuscripts. After the removal of 2073 duplicates, reviewing the remaining articles' titles and abstracts yielded 31 articles for full-text review. Of these, 17 studies were finally included. The studies involved the following training levels: basic life support, adult advanced life support, paediatric and neonatal resuscitations. Most studies (n = 16) evaluated outcomes in simulated, and only one study in actual resuscitations. Studies included in all training contexts showed either neutrality and/or benefits of life support training with specific emphasis on team competencies. Team competencies training improved CPR skill performance and CPR quality. Specific team competencies that improved included leadership, communication, decision-making and task management. No undesirable effects were observed. Meta-analysis was not possible due to significant methodological heterogeneity. Sub-group analysis was impossible due to lack of data. Risk of bias assessment ranged from some concerns to serious. Overall certainty of evidence was rated as low to very low due to risk of bias and imprecision.
CONCLUSION
This systematic review identified very low and low certainty evidence, almost entirely derived from simulation studies. The studies and their findings were heterogenous but suggest that teaching team competencies can improve resuscitation skills performance and CPR quality, as well as improve team competencies, specifically leadership, communication, decision-making, and task management. Further research is required to understand optimal configuration of team competencies training interventions and to understand the effect on clinical outcomes and cost-effectiveness
Beneficial normalization of cardiac repolarization by carnitine in transgenic SQT1 rabbit models.
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Short-QT-syndrome type 1 (SQT1) is a genetic channelopathy caused by gain-of-function variants in HERG underlying the rapid delayed-rectifier K+ current (IKr), leading to QT-shortening, ventricular arrhythmias, and sudden cardiac death. Data on efficient pharmaco-therapy for SQT1 are scarce. In patients with primary carnitine-deficiency, acquired-SQTS has been observed and rescued by carnitine-supplementation. Here, we assessed whether carnitine exerts direct beneficial (prolonging) effects on cardiac repolarization in genetic SQTS.
METHODS AND RESULTS
Adult wild-type (WT) and transgenic SQT1 rabbits (HERG-N588K, gain of IKr) were used. In vivo ECGs, ex vivo monophasic action potentials (APs) in Langendorff-perfused hearts, and cellular ventricular APs and ion currents were assessed at baseline and during L-Carnitine/C16-Carnitine-perfusion. 2D computer simulations were performed to assess reentry-based VT-inducibility.L-Carnitine/C16-Carnitine prolonged QT intervals in WT and SQT1, leading to QT-normalization in SQT1. Similarly, monophasic and cellular AP duration (APD) was prolonged by L-Carnitine/C16-Carnitine in WT and SQT1. As underlying mechanisms, we identified acute effects on the main repolarizing ion currents: IKr-steady, which is pathologically increased in SQT1, was reduced by L-Carnitine/C16-Carnitine and deactivation kinetics were accelerated. Moreover, L-Carnitine/C16-Carnitine decreased IKs-steady and IK1. In silico modelling identified IKr-changes as main factor for L-Carnitine/C16-Carnitine-induced APD-prolongation. 2D-simulations revealed increased sustained reentry-based arrhythmia formation in SQT1 compared to WT, which was decreased to the WT-level when adding carnitine-induced ion current changes.
CONCLUSION
L-Carnitine/C16-Carnitine prolong/normalize QT and whole heart/cellular APD in SQT1 rabbits. These beneficial effects are mediated by acute effects on IKr. L-Carnitine may serve as potential future QT-normalizing, anti-arrhythmic therapy in SQT1
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