| 1. |
- Bass, Gary Alan, 1979-, et al.
(author)
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Techniques for mesoappendix transection and appendix resection: insights from the ESTES SnapAppy study
- 2023
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In: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 17-32
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Journal article (peer-reviewed)abstract
- Introduction: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications. Material and methods: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). Results: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41–0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11–0.96), p = 0.045] complications could be detected when using energy devices. Conclusions: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts.
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| 2. |
- Forssten, Maximilian Peter, 1996-, et al.
(author)
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Surgical management of acute appendicitis during the European COVID-19 second wave: safe and effective
- 2023
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In: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 57-67
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Journal article (peer-reviewed)abstract
- Introduction: The COVID-19 (SARS-CoV-2) pandemic drove acute care surgeons to pivot from long established practice patterns. Early safety concerns regarding increased postoperative complication risk in those with active COVID infection promoted antibiotic-driven non-operative therapy for select conditions ahead of an evidence-base. Our study assesses whether active or recent SARS-CoV-2 positivity increases hospital length of stay (LOS) or postoperative complications following appendectomy. Methods: Data were derived from the prospective multi-institutional observational SnapAppy cohort study. This preplanned data analysis assessed consecutive patients aged ≥ 15years who underwent appendectomy for appendicitis (November 2020–May 2021). Patients were categorized based on SARS-CoV-2 seropositivity: no infection, active infection, and prior infection. Appendectomy method, LOS, and complications were abstracted. The association between SARS-CoV-2 seropositivity and complications was determined using Poisson regression, while the association with LOS was calculated using a quantile regression model. Results: Appendectomy for acute appendicitis was performed in 4047 patients during the second and third European COVID waves. The majority were SARS-CoV-2 uninfected (3861, 95.4%), while 70 (1.7%) were acutely SARS-CoV-2 positive, and 116 (2.8%) reported prior SARS-CoV-2 infection. After confounder adjustment, there was no statistically significant association between SARS-CoV-2 seropositivity and LOS, any complication, or severe complications. Conclusion: During sequential SARS-CoV-2 infection waves, neither active nor prior SARS-CoV-2 infection was associated with prolonged hospital LOS or postoperative complication. Despite early concerns regarding postoperative safety and outcome during active SARS-CoV-2 infection, no such association was noted for those with appendicitis who underwent operative management.
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| 3. |
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| 4. |
- Abazajian, Kevork, et al.
(author)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Journal article (peer-reviewed)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 5. |
- Abbasi, Rasha, et al.
(author)
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IceCube search for neutrinos from GRB 221009A
- 2023
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In: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
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Conference paper (peer-reviewed)abstract
- GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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| 6. |
- Ade, Peter, et al.
(author)
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The Simons Observatory : science goals and forecasts
- 2019
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Journal article (peer-reviewed)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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| 7. |
- Anney, Richard, et al.
(author)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Journal article (peer-reviewed)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 8. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 9. |
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Overview of the JET results
- 2015
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Journal article (peer-reviewed)
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| 10. |
- Pinto, Dalila, et al.
(author)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Journal article (peer-reviewed)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 11. |
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| 12. |
- Ballantyne, Kaye N., et al.
(author)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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In: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Journal article (peer-reviewed)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 13. |
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| 14. |
- Bombarda, F., et al.
(author)
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Runaway electron beam control
- 2019
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Journal article (peer-reviewed)
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| 15. |
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| 16. |
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| 17. |
- Carannante, Ilaria
(author)
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Computational Modelling and Topological Analysis of the striatal microcircuitry in health and Parkinson's disease
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- The basal ganglia are evolutionary conserved nuclei located at the base of the forebrain. They are a central hub in the control of motion and their dysfunctions lead to a variety of movement related disorders, including Parkinson's disease (PD).The largest nucleus and main input stage of the basal ganglia is the striatum. It receives excitatory glutamatergic projections primarily from cortex and thalamus as well as modulatory dopaminergic input from the substantia nigra pars compacta and the ventral tegmental area. Striatal output is mediated by the direct and indirect pathway striatal projection neurons (dSPNs and iSPNs, respectively). In rodents, they account for 95% of the neurons, while the remaining 5% are interneurons, which do not project outside the striatum.The aim of this thesis is to develop an in silico striatal microcircuit in health and PD, and to compare these two networks using electrophysiological simulations and topological analysis.The neuron types included are the striatal projection neurons (dSPN and iSPN) and three of the main interneuron classes: FS, LTS and ChIN. Their multi-compartmental models are based on detailed morphological reconstructions, ion channels expression and electrophysiological ex vivo rodents experimental data from control and PD brains.In Paper A, a comparison between two methods commonly used to model ion channels was presented.In Paper B, the healthy striatal microcircuit was created. We presented a modelling framework called Snudda. It enables the creation of large-scale networks by: placing neurons using appropriate density, predicting synaptic connectivity based on touch detection and a set of pruning rules, setting up external input and modulation, and finally running the simulations. It is written in Python and uses the NEURON simulator.In Paper C, we conducted a computational study on the reciprocal interaction between ChIN and LTS interneurons. Specifically, we simulate the inhibition of LTS via muscarinic M4 receptors following acetylcholine release from ChIN as well as the prolonged depolarization of ChIN subsequent to the release of nitric oxide from LTS.In Paper D, we developed a pipeline to model the NMDA and AMPA postsynaptic currents in striatal neurons following glutamate release from cortex and thalamus. This was done to improve the accuracy of the existing synaptic models.In Paper E, the PD striatal microcircuit was created. First, we modelled the morphological changes in both SPNs and FS as well as the electrophysiological alterations in SPNs. Then we predicted and quantified how the intrastriatal connectivity is altered using anatomically constrained synapse placement and topological analysis of the resulting network. Finally we investigated how the effective glutamatergic drive to SPNs is modified.Overall, in this thesis we further advanced the development of the simulation framework for the study of the basal ganglia function and initiated systematic model-based large-scale computational analysis of their abnormal PD state.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 22. |
- Jin, Shoko, et al.
(author)
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The wide-field, multiplexed, spectroscopic facility WEAVE : Survey design, overview, and simulated implementation
- 2024
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 530:3, s. 2688-2730
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Journal article (peer-reviewed)abstract
- WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, saw first light in late 2022. WEAVE comprises a new 2-deg field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959nm at R similar to 5000, or two shorter ranges at . After summarizing the design and implementation of WEAVE and its data systems, we present the organization, science drivers, and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for similar to 3 million stars and detailed abundances for similar to 1.5 million brighter field and open-cluster stars; (ii) survey similar to 0.4 million Galactic-plane OBA stars, young stellar objects, and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey similar to 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionized gas in z < 0.5 cluster galaxies; (vi) survey stellar populations and kinematics in field galaxies at 0.3 less than or similar to z less than or similar to 0.7; (vii) study the cosmic evolution of accretion and star formation using >1 million spectra of LOFAR-selected radio sources; and (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.
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| 23. |
- Kalliolia, Eirini, et al.
(author)
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A 24-Hour Study of the Hypothalamo-Pituitary Axes in Huntington's Disease.
- 2015
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:10
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Journal article (peer-reviewed)abstract
- Huntington's disease is an inherited neurodegenerative disorder characterised by motor, cognitive and psychiatric disturbances. Patients exhibit other symptoms including sleep and mood disturbances, muscle atrophy and weight loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo-pituitary axes.
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| 24. |
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| 25. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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