| 1. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Drake, TM, et al.
(author)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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In: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Journal article (peer-reviewed)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 4. |
- Eijsbouts, C., et al.
(author)
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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- 2021
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
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Journal article (peer-reviewed)abstract
- Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
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| 5. |
- Torbert, R. B., et al.
(author)
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Electron-scale dynamics of the diffusion region during symmetric magnetic reconnection in space
- 2018
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In: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 362:6421, s. 1391-1395
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Journal article (peer-reviewed)abstract
- Magnetic reconnection is an energy conversion process that occurs in many astrophysical contexts including Earth's magnetosphere, where the process can be investigated in situ by spacecraft. On 11 July 2017, the four Magnetospheric Multiscale spacecraft encountered a reconnection site in Earth's magnetotail, where reconnection involves symmetric inflow conditions. The electron-scale plasma measurements revealed (i) super-Alfvenic electron jets reaching 15,000 kilometers per second; (ii) electron meandering motion and acceleration by the electric field, producing multiple crescent-shaped structures in the velocity distributions; and (iii) the spatial dimensions of the electron diffusion region with an aspect ratio of 0.1 to 0.2, consistent with fast reconnection. The well-structured multiple layers of electron populations indicate that the dominant electron dynamics are mostly laminar, despite the presence of turbulence near the reconnection site.
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| 6. |
- Lavraud, B., et al.
(author)
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Currents and associated electron scattering and bouncing near the diffusion region at Earth's magnetopause
- 2016
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 43:7, s. 3042-3050
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Journal article (peer-reviewed)abstract
- Based on high-resolution measurements from NASA's Magnetospheric Multiscale mission, we present the dynamics of electrons associated with current systems observed near the diffusion region of magnetic reconnection at Earth's magnetopause. Using pitch angle distributions (PAD) and magnetic curvature analysis, we demonstrate the occurrence of electron scattering in the curved magnetic field of the diffusion region down to energies of 20 eV. We show that scattering occurs closer to the current sheet as the electron energy decreases. The scattering of inflowing electrons, associated with field-aligned electrostatic potentials and Hall currents, produces a new population of scattered electrons with broader PAD which bounce back and forth in the exhaust. Except at the center of the diffusion region the two populations are collocated and appear to behave adiabatically: the inflowing electron PAD focuses inward (toward lower magnetic field), while the bouncing population PAD gradually peaks at 90 degrees away from the center (where it mirrors owing to higher magnetic field and probable field-aligned potentials).
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| 7. |
- Farrugia, C. J., et al.
(author)
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MMS Observations of Reconnection at Dayside Magnetopause Crossings During Transitions of the Solar Wind to Sub-Alfvénic Flow
- 2017
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In: Journal of Geophysical Research - Space Physics. - : Blackwell Publishing Ltd. - 2169-9380 .- 2169-9402. ; 122:10, s. 9934-9951
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Journal article (peer-reviewed)abstract
- We present MMS observations during two dayside magnetopause crossings under hitherto unexamined conditions: (i) when the bow shock is weakening and the solar wind transitioning to sub-Alfvénic flow and (ii) when it is reforming. Interplanetary conditions consist of a magnetic cloud with (i) a strong B (∼20 nT) pointing south and (ii) a density profile with episodic decreases to values of ∼0.3 cm−3 followed by moderate recovery. During the crossings the magnetosheath magnetic field is stronger than the magnetosphere field by a factor of ∼2.2. As a result, during the outbound crossing through the ion diffusion region, MMS observed an inversion of the relative positions of the X and stagnation (S) lines from that typically the case: the S line was closer to the magnetosheath side. The S line appears in the form of a slow expansion fan near which most of the energy dissipation is taking place. While in the magnetosphere between the crossings, MMS observed strong field and flow perturbations, which we argue to be due to kinetic Alfvén waves. During the reconnection interval, whistler mode waves generated by an electron temperature anisotropy (Te⊥>Te∥) were observed. Another aim of the paper is to distinguish bow shock-induced field and flow perturbations from reconnection-related signatures. The high-resolution MMS data together with 2-D hybrid simulations of bow shock dynamics helped us to distinguish between the two sources. We show examples of bow shock-related effects (such as heating) and reconnection effects such as accelerated flows satisfying the Walén relation.
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| 8. |
- Farrugia, C. J., et al.
(author)
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Effects in the Near-Magnetopause Magnetosheath Elicited by Large-Amplitube Alfvenic Fluctuations Terminating in a Field and Flow Discontinuity
- 2018
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In: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 123:11, s. 8983-9004
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Journal article (peer-reviewed)abstract
- In this paper we report on a sequence of large-amplitude Alfvenic fluctuations terminating in a field and flow discontinuity and their effects on electromagnetic fields and plasmas in the near-magnetopause magnetosheath. An arc-polarized structure in the magnetic field was observed by the Time History of Events and Macroscale Interactions during Substorms-C in the solar wind, indicative of nonlinear Alfven waves. It ends with a combined tangential discontinuity/vortex sheet, which is strongly inclined to the ecliptic plane and at which there is a sharp rise in the density and a drop in temperature. Several effects resulting from this structure were observed by the Magnetospheric Multiscale spacecraft in the magnetosheath close to the subsolar point (11:30 magnetic local time) and somewhat south of the geomagnetic equator (-33 degrees magnetic latitude): (i) kinetic Alfven waves; (ii) a peaking of the electric and magnetic field strengths where E . J becomes strong and negative (-1 nW/m(3)) just prior to an abrupt dropout of the fields; (iii) evolution in the pitch angle distribution of energetic (a few tens of kilo-electron-volts) ions (H+, Hen+, and On+) and electrons inside a high-density region, which we attribute to gyrosounding of the tangential discontinuity/vortex sheet structure passing by the spacecraft; (iv) field-aligned acceleration of ions and electrons that could be associated with localized magnetosheath reconnection inside the high-density region; and (v) variable and strong flow changes, which we argue to be unrelated to reconnection at partial magnetopause crossings and likely result from deflections of magnetosheath flow by a locally deformed, oscillating magnetopause.
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| 9. |
- Kacem, I., et al.
(author)
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Magnetic Reconnection at a Thin Current Sheet Separating Two Interlaced Flux Tubes at the Earth's Magnetopause
- 2018
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In: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 123:3, s. 1779-1793
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Journal article (peer-reviewed)abstract
- The occurrence of spatially and temporally variable reconnection at the Earth's magnetopause leads to the complex interaction of magnetic fields from the magnetosphere and magnetosheath. Flux transfer events (FTEs) constitute one such type of interaction. Their main characteristics are (1) an enhanced core magnetic field magnitude and (2) a bipolar magnetic field signature in the component normal to the magnetopause, reminiscent of a large-scale helicoidal flux tube magnetic configuration. However, other geometrical configurations which do not fit this classical picture have also been observed. Using high-resolution measurements from the Magnetospheric Multiscale mission, we investigate an event in the vicinity of the Earth's magnetopause on 7 November 2015. Despite signatures that, at first glance, appear consistent with a classic FTE, based on detailed geometrical and dynamical analyses as well as on topological signatures revealed by suprathermal electron properties, we demonstrate that this event is not consistent with a single, homogenous helicoidal structure. Our analysis rather suggests that it consists of the interaction of two separate sets of magnetic field lines with different connectivities. This complex three-dimensional interaction constructively conspires to produce signatures partially consistent with that of an FTE. We also show that, at the interface between the two sets of field lines, where the observed magnetic pileup occurs, a thin and strong current sheet forms with a large ion jet, which may be consistent with magnetic flux dissipation through magnetic reconnection in the interaction region.
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| 10. |
- Matsui, H., et al.
(author)
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Dipolarization in the inner magnetosphere during a geomagnetic storm on 7 October 2015
- 2016
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In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 43:18, s. 9397-9405
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Journal article (peer-reviewed)abstract
- A dipolarization event was observed by the Magnetospheric Multiscale (MMS) spacecraft at L = 3.8 and 19.8 magnetic local time starting at similar to 23:42:36 UT on 7 October 2015. The magnetic and electric fields showed initially coherent variations between the spacecraft. The sunward convection turned tailward after the dipolarization. The observation is interpreted in terms of the pressure balance or the momentum equation. This was followed by a region traversed where the fields were irregular. The scale length was of the order of the ion gyroradius, suggesting the kinetic nature of the fluctuations. Combination of the multi-instrument, multispacecraft data reveals a more detailed picture of the dipolarization event in the inner magnetosphere. Conjunction ionosphere-plasmasphere observations from DMSP, two-dimensional GPS total electron content, the Millstone Hill midlatitude incoherent scatter radar, and AMPERE measurements imply that MMS observations are located on the poleward edge of the ionospheric trough where Region 2 field-aligned currents flow.
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| 11. |
- Schiava, M., et al.
(author)
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Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study
- 2022
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In: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 93:10, s. 1099-1111
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Journal article (peer-reviewed)abstract
- Background Valosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype-phenotype correlations. Methods Descriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene. Results Two hundred and fifty-five patients (70.0% males) were included in the study. Mean age was 56.8 +/- 9.6 years and mean age of onset 45.6 +/- 9.3 years. Mean diagnostic delay was 7.7 +/- 6 years. Symmetric lower limb weakness was reported in 50% at onset progressing to generalised muscle weakness. Other common symptoms were ventilatory insufficiency 40.3%, PDB 28.2%, dysautonomia 21.4% and FTD 14.3%. Fifty-seven genetic variants were identified, 18 of these no previously reported. c.464G>A (p.Arg155His) was the most frequent variant, identified in the 28%. Full time wheelchair users accounted for 19.1% with a median time from disease onset to been wheelchair user of 8.5 years. Variant c.463C>T (p.Arg155Cys) showed an earlier onset (37.8 +/- 7.6 year) and a higher frequency of axial and upper limb weakness, scapular winging and cognitive impairment. Forced vital capacity (FVC) below 50% was as risk factor for being full-time wheelchair user, while FVC Conclusion This study expands the knowledge on the phenotypic presentation, natural history, genotype-phenotype correlations and risk factors for disease progression of VCP disease and is useful to improve the care provided to patient with this complex disease.
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| 12. |
- Zheng, TH, et al.
(author)
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Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
- 2021
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1538-1549
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Journal article (peer-reviewed)abstract
- Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.DesignWe conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.ResultsWe demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.ConclusionHEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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| 13. |
- Fadanelli, S., et al.
(author)
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Four-Spacecraft Measurements of the Shape and Dimensionality of Magnetic Structures in the Near-Earth Plasma Environment
- 2019
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In: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 124:8, s. 6850-6868
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Journal article (peer-reviewed)abstract
- We present a new method for determining the main relevant features of the local magnetic field configuration, based entirely on the knowledge of the magnetic field gradient four‐spacecraft measurements. The method, named “magnetic configuration analysis” (MCA), estimates the spatial scales on which the magnetic field varies locally. While it directly derives from the well‐known magnetic directional derivative and magnetic rotational analysis procedures (Shi et al., 2005, htpps://doi.org/10.1029/2005GL022454; Shen et al., 2007, https://doi.org/10.1029/2005JA011584), MCA was specifically designed to address the actual magnetic field geometry. By applying MCA to multispacecraft data from the Magnetospheric Multiscale (MMS) satellites, we perform both case and statistical analyses of local magnetic field shape and dimensionality at very high cadence and small scales. We apply this technique to different near‐Earth environments and define a classification scheme for the type of configuration observed. While our case studies allow us to benchmark the method with those used in past works, our statistical analysis unveils the typical shape of magnetic configurations and their statistical distributions. We show that small‐scale magnetic configurations are generally elongated, displaying forms of cigar and blade shapes, but occasionally being planar in shape like thin pancakes (mostly inside current sheets). Magnetic configurations, however, rarely show isotropy in their magnetic variance. The planar nature of magnetic configurations and, most importantly, their scale lengths strongly depend on the plasma β parameter. Finally, the most invariant direction is statistically aligned with the electric current, reminiscent of the importance of electromagnetic forces in shaping the local magnetic configuration.
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| 14. |
- Farrugia, C. J., et al.
(author)
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Magnetospheric Multiscale Mission observations and non-force free modeling of a flux transfer event immersed in a super-Alfvenic flow
- 2016
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In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 43:12, s. 6070-6077
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Journal article (peer-reviewed)abstract
- We analyze plasma, magnetic field, and electric field data for a flux transfer event (FTE) to highlight improvements in our understanding of these transient reconnection signatures resulting from high-resolution data. The similar to 20 s long, reverse FTE, which occurred south of the geomagnetic equator near dusk, was immersed in super-Alfvenic flow. The field line twist is illustrated by the behavior of flows parallel/perpendicular to the magnetic field. Four-spacecraft timing and energetic particle pitch angle anisotropies indicate a flux rope (FR) connected to the Northern Hemisphere and moving southeast. The flow forces evidently overcame the magnetic tension. The high-speed flows inside the FR were different from those outside. The external flows were perpendicular to the field as expected for draping of the external field around the FR. Modeling the FR analytically, we adopt a non-force free approach since the current perpendicular to the field is nonzero. It reproduces many features of the observations.
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| 15. |
- Torbert, R. B., et al.
(author)
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Estimates of terms in Ohm's law during an encounter with an electron diffusion region
- 2016
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In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 43:12, s. 5918-5925
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Journal article (peer-reviewed)abstract
- We present measurements from the Magnetospheric Multiscale (MMS) mission taken during a reconnection event on the dayside magnetopause which includes a passage through an electron diffusion region (EDR). The four MMS satellites were separated by about 10 km such that estimates of gradients and divergences allow a reasonable estimate of terms in the generalized Ohm's law, which is key to investigating the energy dissipation during reconnection. The strength and character of dissipation mechanisms determines how magnetic energy is released. We show that both electron pressure gradients and electron inertial effects are important, but not the only participants in reconnection near EDRs, since there are residuals of a few mV/m (similar to 30-50%) of E + U-e x B (from the sum of these two terms) during the encounters. These results are compared to a simulation, which exhibits many of the observed features, but where relatively little residual is present.
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| 16. |
- Vernisse, Y., et al.
(author)
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Signatures of complex magnetic topologies from multiple reconnection sites induced by Kelvin-Helmholtz instability
- 2016
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In: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 121:10, s. 9926-9939
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Journal article (peer-reviewed)abstract
- The Magnetospheric Multiscale mission has demonstrated the frequent presence of reconnection exhausts at thin current sheets within Kelvin-Helmholtz (KH) waves at the flank magnetopause. Motivated by these recent observations, we performed a statistical analysis of the boundary layers on the magnetosheath side of all KH current sheets on 8 September 2015. We show 86% consistency between the exhaust flows and particle leakage in the magnetosheath boundary layers but further highlight the very frequent presence of additional boundary layer signatures that do not come from the locally observed reconnection exhausts. These additional electron and ion boundary layers, of various durations and at various positions with respect to the leading and trailing boundaries of the KH waves, signal connections to reconnection sites at other locations. Based on the directionality and extent of these layers, we provide an interpretation whereby complex magnetic topologies can arise within KH waves from the combination of reconnection in the equatorial plane and at midlatitudes in the Southern and Northern Hemispheres, where additional reconnection sites are expected to be triggered by the three-dimensional field lines interweaving induced by the KH waves at the flanks (owing to differential flow and magnetic field shear with latitude). The present event demonstrates that the three-dimensional development of KH waves can induce plasma entry (through reconnection at both midlatitude and equatorial regions) already sunward of the terminator where the instability remains in its linear stage.
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| 17. |
- Matsui, H., et al.
(author)
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A Multi-Instrument Study of a Dipolarization Event in the Inner Magnetosphere
- 2021
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In: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 126:5
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Journal article (peer-reviewed)abstract
- A dipolarization of the background magnetic field was observed during a conjunction of the Magnetospheric Multiscale (MMS) spacecraft and Van Allen Probe B on September 22, 2018. The spacecraft were located in the inner magnetosphere at L similar to 6-7 just before midnight magnetic local time (MLT). The radial separation between MMS and Probe B was similar to 1R(E). Gradual dipolarization or an increase of the northward component B-Z of the background field occurred on a timescale of minutes. Exploration of energization and Radiation in Geospace located 0.5 MLT eastward at a similar L shell also measured a gradual increase. The spatial scale was of the order of 1 R-E. On top of that, MMS and Probe B measured B-Z increases, and a decrease in one case, on a timescale of seconds, accompanied by large electric fields with amplitudes > several tens of mV/m. Spatial scale lengths were of the order of the ion inertial length and the ion gyroradius. The inertial term in the momentum equation and the Hall term in the generalized Ohm's law were sometimes non-negligible. These small-scale variations are discussed in terms of the ballooning/interchange instability and kinetic Alfven waves among others. It is inferred that physics of multiple scales was involved in the dynamics of this dipolarization event.
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| 18. |
- Alm, L., et al.
(author)
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EDR signatures observed by MMS in the 16 October event presented in a 2-D parametric space
- 2017
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In: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 122:3, s. 3262-3276
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Journal article (peer-reviewed)abstract
- We present a method for mapping the position of satellites relative to the X line using the measured B-L and B-N components of the magnetic field and apply it to the Magnetospheric multiscale (MMS) encounter with the electron diffusion region (EDR) which occurred on 13:07 UT on 16 October 2015. Mapping the data to our parametric space succeeds in capturing many of the signatures associated with magnetic reconnection and the electron diffusion region. This offers a method for determining where in the reconnection region the satellites were located. In addition, parametric mapping can also be used to present data from numerical simulations. This facilitates comparing data from simulations with data from in situ observations as one can avoid the complicated process using boundary motion analysis to determine the geometry of the reconnection region. In parametric space we can identify the EDR based on the collocation of several reconnection signatures, such as electron nongyrotropy, electron demagnetization, parallel electric fields, and energy dissipation. The EDR extends 2-3km in the normal direction and in excess of 20km in the tangential direction. It is clear that the EDR occurs on the magnetospheric side of the topological X line, which is expected in asymmetric reconnection. Furthermore, we can observe a north-south asymmetry, where the EDR occurs north of the peak in out-of-plane current, which may be due to the small but finite guide field.
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| 19. |
- Erickson, P. J., et al.
(author)
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Multipoint MMS observations of fine-scale SAPS structure in the inner magnetosphere
- 2016
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In: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:14, s. 7294-7300
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Journal article (peer-reviewed)abstract
- We present detailed observations of dynamic, fine-scale inner magnetosphere-ionosphere coupling at approximate to 3.9R(E) in the Region 2 Birkeland field-aligned current (FAC). We find that observed electrodynamic spatial/temporal scales are primarily characteristic of magnetically mapped ionospheric structure. On 15 September 2015, conjugate Magnetospheric Multiscale (MMS) spacecraft and Millstone Hill radar observations show plasmasphere boundary region subauroral polarization stream (SAPS) electric fields at L = 4.0-4.2 near 21 MLT. MMS observations reveal high-altitude approximate to 1mV/m fine-scale radial and azimuthal electric field perturbations over 0.15L with high spatial coherence over 2-3min and show outward motion within a broader FAC of approximate to 0.12A/m(2). Our analysis shows that MMS electric field fluctuations are most likely reflective of SAPS ionospheric structure at scales of approximate to 22km and with ionospheric closure of small-scale filamentary FAC perturbations. The results highlight the ionosphere's importance in regulating fine-scale magnetosphere-ionosphere structure.
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| 20. |
- Farrugia, C. J., et al.
(author)
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"Crater" flux transfer events : Highroad to the X line?
- 2011
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In: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202. ; 116:2
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Journal article (peer-reviewed)abstract
- We examine Cluster observations of a so-called magnetosphere "crater FTE," employing data from five instruments (FGM, CIS, EDI, EFW, and WHISPER), some at the highest resolution. The aim of doing this is to deepen our understanding of the reconnection nature of these events by applying recent advances in the theory of collisionless reconnection and in detailed observational work. Our data support the hypothesis of a stratified structure with regions which we show to be spatial structures. We support the bulge-like topology of the core region (R3) made up of plasma jetting transverse to reconnected field lines. We document encounters with a magnetic separatrix as a thin layer embedded in the region (R2) just outside the bulge, where the speed of the protons flowing approximately parallel to the field maximizes: (1) short (fraction of a sec) bursts of enhanced electric field strengths (up to similar to 30 mV/m) and (2) electrons flowing against the field toward the X line at approximately the same time as the bursts of intense electric fields. R2 also contains a density decrease concomitant with an enhanced magnetic field strength. At its interface with the core region, R3, electric field activity ceases abruptly. The accelerated plasma flow profile has a catenary shape consisting of beams parallel to the field in R2 close to the R2/R3 boundary and slower jets moving across the magnetic field within the bulge region. We detail commonalities our observations of crater FTEs have with reconnection structures in other scenarios. We suggest that in view of these properties and their frequency of occurrence, crater FTEs are ideal places to study processes at the separatrices, key regions in magnetic reconnection. This is a good preparation for the MMS mission.
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| 21. |
- Torbert, R. B., et al.
(author)
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Structure and Dissipation Characteristics of an Electron Diffusion Region Observed by MMS During a Rapid, Normal-Incidence Magnetopause Crossing
- 2017
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In: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 122:12, s. 11901-11916
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Journal article (peer-reviewed)abstract
- On 22 October 2016, the Magnetospheric Multiscale (MMS) spacecraft encountered the electron diffusion region (EDR) when the magnetosheath field was southward, and there were signatures of fast reconnection, including flow jets, Hall fields, and large power dissipation. One rapid, normal-incidence crossing, during which the EDR structure was almost stationary in the boundary frame, provided an opportunity to observe the spatial structure for the zero guide field case of magnetic reconnection. The reconnection electric field was determined unambiguously to be 2-3 mV/m. There were clear signals of fluctuating parallel electric fields, up to 6 mV/m on the magnetosphere side of the diffusion region, associated with a Hall-like parallel current feature on the electron scale. The width of the main EDR structure was determined to be similar to 2 km (1.8 de). Although the MMS spacecraft were in their closest tetrahedral separation of similar to 8 km, the divergences and curls for these thin current structures could therefore not be computed in the usual manner. A method is developed to determine these quantities on a much smaller scale and applied to compute the normal component of terms in the generalized Ohm's law for the positions of each individual spacecraft (not a barocentric average). Although the gradient pressure term has a qualitative dependence that follows the observed variation of E + Ve x B, the quantitative magnitude of these terms differs by more than a factor of 2, which is shown to be greater than the respective errors. Thus, future research is required to find the manner in which Ohm's law is balanced. Plain Language Summary The Magnetospheric Multiscale (MMS) spacecraft observed the spatial structure of the region where magnetic energy is converted to particle flows and heat. New features of currents and fields parallel to the magnetic field are analyzed. Some discrepancies with present computer simulations are found within this region.
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| 22. |
- White, H, et al.
(author)
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A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real time quantitative PCR.
- 2015
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 29:2, s. 369-376
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Journal article (peer-reviewed)abstract
- Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukemia, but there is substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 10(6), 1.08±0.11 × 10(5), 1.03±0.10 × 10(4), 1.02±0.09 × 10(3), 1.04±0.10 × 10(2) and 10.0±1.5 copies/μL. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise the numbers of measured transcripts of e14a2 BCR-ABL1 and three control genes; ABL1, BCR and GUSB. The set of 6 plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (http://irmm.jrc.ec.europa.eu; CRM code ERM-AD623a-f).Leukemia accepted article preview online, 18 July 2014; doi:10.1038/leu.2014.217.
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| 23. |
- Alm, L., et al.
(author)
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Differing Properties of Two Ion-Scale Magnetopause Flux Ropes
- 2018
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In: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 123:1, s. 114-131
-
Journal article (peer-reviewed)abstract
- In this paper, we present results from the Magnetospheric Multiscale constellation encountering two ion-scale, magnetopause flux ropes. The two flux ropes exhibit very different properties and internal structure. In the first flux rope, there are large differences in the currents observed by different satellites, indicating variations occurring over sub-d(i) spatial scales, and time scales on the order of the ion gyroperiod. In addition, there is intense wave activity and particle energization. The interface between the two flux ropes exhibits oblique whistler wave activity. In contrast, the second flux rope is mostly quiescent, exhibiting little activity throughout the encounter. Changes in the magnetic topology and field line connectivity suggest that we are observing flux rope coalescence.
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| 24. |
- Argall, M. R., et al.
(author)
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Electron Dynamics Within the Electron Diffusion Region of Asymmetric Reconnection
- 2018
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In: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 123:1, s. 146-162
-
Journal article (peer-reviewed)abstract
- We investigate the agyrotropic nature of electron distribution functions and their substructure to illuminate electron dynamics in a previously reported electron diffusion region (EDR) event. In particular, agyrotropy is examined as a function of energy to reveal detailed finite Larmor radius effects for the first time. It is shown that the previously reported approximate to 66eV agyrotropic "crescent" population that has been accelerated as a result of reconnection is evanescent in nature because it mixes with a denser, gyrotopic background. Meanwhile, accelerated agyrotropic populations at 250 and 500eV are more prominent because the background plasma at those energies is more tenuous. Agyrotropy at 250 and 500eV is also more persistent than at 66eV because of finite Larmor radius effects; agyrotropy is observed 2.5 ion inertial lengths from the EDR at 500eV, but only in close proximity to the EDR at 66eV. We also observe linearly polarized electrostatic waves leading up to and within the EDR. They have wave normal angles near 90 degrees, and their occurrence and intensity correlate with agyrotropy. Within the EDR, they modulate the flux of 500eV electrons travelling along the current layer. The net electric field intensifies the reconnection current, resulting in a flow of energy from the fields into the plasma. Plain Language Summary The process of reconnection involves an explosive transfer of magnetic energy into particle energy. When energetic particles contact modern technology such as satellites, cell phones, or other electronic devices, they can cause random errors and failures. Exactly how particles are energized via reconnection, however, is still unknown. Fortunately, the Magnetospheric Multiscale mission is finally able to detect and analyze reconnection processes. One recent finding is that energized particles take on a crescent-shaped configuration in the vicinity of reconnection and that this crescent shape is related to the energy conversion process. In our paper, we explain why the crescent shape has not been observed until now and inspect particle motions to determine what impact it has on energy conversion. When reconnection heats the plasma, the crescent shape forms from the cool, tenuous particles. As plasmas from different regions mix, dense, nonheated plasma obscures the crescent shape in our observations. The highest-energy particle population created by reconnection, though, also contains features of the crescent shape that are more persistent but appear less dramatically in the data.
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| 25. |
- Beyder, Arthur, et al.
(author)
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Loss-of-Function of the Voltage-Gated Sodium Channel Na(V)1.5 (Channelopathies) in Patients With Irritable Bowel Syndrome
- 2014
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 146:7, s. 1659-1668
-
Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: SCN5A encodes the a-subunit of the voltage-gated sodium channel Na(V)1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of Na(V)1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted Na(V)1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-Na(V)1.5 had the greatest effect in reducing Na(V)1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt Na(V)1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.
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| 26. |
- Beyder, Arthur, et al.
(author)
-
Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome.
- 2014
-
In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 146:7
-
Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5.METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls.RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted NaV1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-NaV1.5 had the greatest effect in reducing NaV1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS.CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt NaV1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.
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| 27. |
- Knowles, C H, et al.
(author)
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Quantitation of cellular components of the enteric nervous system in the normal human gastrointestinal tract - report on behalf of the Gastro 2009 International Working Group.
- 2011
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 23:2, s. 115-124
-
Journal article (peer-reviewed)abstract
- Background Patients with gastrointestinal neuromuscular diseases may undergo operative procedures that yield tissue appropriate to diagnosis of underlying neuromuscular pathology. Critical to accurate diagnosis is the determination of limits of normality based on the study of control human tissues. Although robust diagnostic criteria exist for many qualitative alterations in the neuromuscular apparatus, these do not include quantitative values due to lack of adequate control data. Purpose The aim of this report was to summarize all relevant available published quantitative data for elements of the human enteric nervous system (neuronal cell bodies, glial cells, and nerve fibers) from the perspective of the practicing pathologist. Forty studies meeting inclusion criteria were systematically reviewed with data tabulated in detail and discussed in the context of methodological variations and limitations. The results reveal a lack of concordance between observations of different investigators resulting in data insufficient to produce robust normal ranges. This diversity highlights the need to standardize the way pathologists collect, process, and quantitate neuronal and glial elements in enteric neuropathologic samples, as suggested by recent international guidelines on gastrointestinal neuromuscular pathology.
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| 28. |
- Boenink, Rianne, et al.
(author)
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Trends in kidney transplantation rate across Europe : a study from the ERA Registry
- 2023
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In: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 38:6, s. 1528-1539
-
Journal article (peer-reviewed)abstract
- Background. The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries. Methods. The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated. Results. The total KT rate in the 40 participating countries increased with 1.9% annually [95% confidence interval (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East-West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.). Conclusions. The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.
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| 29. |
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| 30. |
- Matsui, H., et al.
(author)
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Characteristics of storm time electric fields in the inner magnetosphere derived from Cluster data
- 2010
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115, s. A11215-
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Journal article (peer-reviewed)abstract
- Storm-time electric fields in the inner magnetosphere measured by Cluster are reported in this study. First, we show two events around the time when Dst index is at a minimum. The electric field possibly related to subauroral ion drifts and/or undershielding is measured inside the inner edge of the electron plasma sheet in the eveningside. For the second event observed in the nightside, the electric field is partly related to dipolarization and is considered as inductive. An electric field without coincident magnetic signatures is also observed. Spatial coherence of the electric field is not large when we check multispacecraft data. It is inferred that the electric field in the magnetotail penetrates inside the region 1 current, while it is not clear about the electric field within the region 2 current from our data. Then superposed epoch analyses using 71 storms are performed. Electric fields at R = 3.5-6R(E) and less than 25 degrees of magnetic latitudes are enhanced around the minimum Dst at all magnetic local times. Electric fields during the recovery phase decay on a time scale shorter than that of Dst index, which could be interpreted in terms of the relation between electric field and ring current during that storm phase. AC electric fields are generally larger than DC electric fields, indicating that the former component might play some role in accelerating ring current particles. These results will be useful to update our empirical electric field model.
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| 31. |
- Matsui, H., et al.
(author)
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Relativistic Electron Increase During Chorus Wave Activities on the 6-8 March 2016 Geomagnetic Storm
- 2017
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In: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 122:11, s. 11302-11319
-
Journal article (peer-reviewed)abstract
- There was a geomagnetic storm on 6-8 March 2016, in which Van Allen Probes A and B separated by similar to 2.5 h measured increase of relativistic electrons with energies approximately several hundred keV to 1 MeV. Simultaneously, chorus waves were measured by both Van Allen Probes and Magnetospheric Multiscale (MMS) mission. Some of the chorus elements were rising tones, possibly due to nonlinear effects. These measurements are compared with a nonlinear theory of chorus waves incorporating the inhomogeneity ratio and the field equation. From this theory, a chorus wave profile in time and one-dimensional space is simulated. Test particle calculations are then performed in order to examine the energization rate of electrons. Some electrons are accelerated, although more electrons are decelerated. The measured time scale of the electron increase is inferred to be consistent with this nonlinear theory.
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| 32. |
- Wjnhoven, TMA, et al.
(author)
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WHO European Childhood Obesity Surveillance Initiative: School nutrition environment and body mass index in primary schools.
- 2014
-
In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601 .- 1661-7827. ; 2014:11, s. 11261-11285
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Schools are important settings for the promotion of a healthy diet and sufficient physical activity and thus overweight prevention. OBJECTIVE: To assess differences in school nutrition environment and body mass index (BMI) in primary schools between and within 12 European countries. METHODS: Data from the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative (COSI) were used (1831 and 2045 schools in 2007/2008 and 2009/2010, respectively). School personnel provided information on 18 school environmental characteristics on nutrition and physical activity. A school nutrition environment score was calculated using five nutrition-related characteristics whereby higher scores correspond to higher support for a healthy school nutrition environment. Trained field workers measured children's weight and height; BMI-for-age (BMI/A) Z-scores were computed using the 2007 WHO growth reference and, for each school, the mean of the children's BMI/A Z-scores was calculated. RESULTS: Large between-country differences were found in the availability of food items on the premises (e.g., fresh fruit could be obtained in 12%-95% of schools) and school nutrition environment scores (range: 0.30-0.93). Low-score countries (Bulgaria, Czech Republic, Greece, Hungary, Latvia and Lithuania) graded less than three characteristics as supportive. High-score (≥0.70) countries were Ireland, Malta, Norway, Portugal, Slovenia and Sweden. The combined absence of cold drinks containing sugar, sweet snacks and salted snacks were more observed in high-score countries than in low-score countries. Largest within-country school nutrition environment scores were found in Bulgaria, Czech Republic, Greece, Hungary, Latvia and Lithuania. All country-level BMI/A Z-scores were positive (range: 0.20-1.02), indicating higher BMI values than the 2007 WHO growth reference. With the exception of Norway and Sweden, a country-specific association between the school nutrition environment score and the school BMI/A Z-score was not observed. CONCLUSIONS: Some European countries have implemented more school policies that are supportive to a healthy nutrition environment than others. However, most countries with low school nutrition environment scores also host schools with supportive school environment policies, suggesting that a uniform school policy to tackle the "unhealthy" school nutrition environment has not been implemented at the same level throughout a country and may underline the need for harmonized school policies.
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| 33. |
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| 34. |
- Daelman, Bo, et al.
(author)
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Frailty and cognitive function in middle-aged and older adults with congenital heart disease
- 2024
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In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 83:12, s. 1149-1159
-
Journal article (peer-reviewed)abstract
- Background: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential.Objectives: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits.Methods: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment.Results: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income.Conclusions: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.
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| 35. |
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| 36. |
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| 37. |
- Iveson, Timothy J., et al.
(author)
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3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT) : an international, randomised, phase 3, non-inferiority trial
- 2018
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In: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 19:4, s. 562-578
-
Journal article (peer-reviewed)abstract
- Background: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.Methods: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1: 1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1.13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.Findings: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76.7% (95% CI 75.1-78.2) for the 3 month group and 77.1% (75.6-78.6) for the 6 month group, giving a hazard ratio of 1.006 (0.909-1.114, test for non-inferiority p=0.012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).Interpretation: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.
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| 38. |
- Knowles, Charles H., et al.
(author)
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Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group
- 2009
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 118:2, s. 271-301
-
Journal article (peer-reviewed)abstract
- The term gastrointestinal neuromuscular disease describes a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular, including interstitial cell of Cajal, dysfunction. Such disorders commonly have impaired motor activity, i.e. slowed or obstructed transit with radiological evidence of transient or persistent visceral dilatation. Whilst sensorimotor abnormalities have been demonstrated by a variety of methods in these conditions, standards for histopathological reporting remain relatively neglected. Significant differences in methodologies and expertise continue to confound the reliable delineation of normality and specificity of particular pathological changes for disease. Such issues require urgent clarification to standardize acquisition and handling of tissue specimens, interpretation of findings and make informed decisions on risk-benefit of full-thickness tissue biopsy of bowel or other diagnostic procedures. Such information will also allow increased certainty of diagnosis, facilitating factual discussion between patients and caregivers, as well as giving prognostic and therapeutic information. The following report, produced by an international working group, using established consensus methodology, presents proposed guidelines on histological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology. The report addresses the main areas of histopathological practice as confronted by the pathologist, including suction rectal biopsy and full-thickness tissue obtained with diagnostic or therapeutic intent. For each, indications, safe acquisition of tissue, histological techniques, reporting and referral recommendations are presented.
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| 39. |
- Knowles, Charles H., et al.
(author)
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The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group
- 2010
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 59:7, s. 882-887
-
Journal article (peer-reviewed)abstract
- Objective Guidelines on histopathological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology have been produced recently by an international working group (IWG). These addressed the important but relatively neglected areas of histopathological practice of the general pathologist, including suction rectal biopsy and full-thickness intestinal tissue. Recommendations were presented for the indications, safe acquisition of tissue, histological techniques, reporting and referral of such histological material. Design Consensual processes undertaken by the IWG and following established guideline decision group methodologies. Results and conclusion This report presents a contemporary and structured classification of gastrointestinal neuromuscular pathology based on defined histopathological criteria derived from the existing guidelines. In recognition of its origins and first presentation in London at the World Congress of Gastroenterology 2009, this has been named 'The London Classification'. The implementation of this classification should allow some diagnostic standardisation, but should necessarily be viewed as a starting point for future modification as new data become available.
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| 40. |
- Moestl, C., et al.
(author)
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The structure of an earthward propagating magnetic flux rope early in its evolution : comparison of methods
- 2009
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In: Annales Geophysicae. - 0992-7689 .- 1432-0576. ; 27:5, s. 2215-2224
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Journal article (peer-reviewed)abstract
- We analyze a magnetic signature associated with the leading edge of a bursty bulk flow observed by Cluster at -19 R-E downtail on 22 August 2001. A distinct rotation of the magnetic field was seen by all four spacecraft. This event was previously examined by Slavin et al. (2003b) using both linear force-free modeling as well as a curlometer technique. Extending this work, we apply here single- and multi-spacecraft Grad-Shafranov (GS) reconstruction techniques to the Cluster observations and find good evidence that the structure encountered is indeed a magnetic flux rope and contains helical magnetic field lines. We find that the flux rope has a diameter of approximately 1 R-E, an axial field of 26.4 nT, a velocity of approximate to 650 km/s, a total axial current of 0.16 MA and magnetic fluxes of order 10(5) Wb. The field line twist is estimated as half a turn per RE. The invariant axis is inclined at 40 degrees to the ecliptic plane and 10 degrees to the GSM equatorial plane. The flux rope has a force-free core and non-force-free boundaries. When we compare and contrast our results with those obtained from minimum variance, single-spacecraft force-free fitting and curlometer techniques, we find in general fair agreement, but also clear differences such as a higher inclination of the axis to the ecliptic. We further conclude that single- spacecraft methods have limitations which should be kept in mind when applied to THEMIS observations, and that non-force-free GS and curlometer techniques are to be preferred in their analysis. Some properties we derived for this earthward - moving structure are similar to those inferred by Lui et al. (2007), using a different approach, for a tailward-moving flux rope observed during the expansion phase of the same substorm.
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| 41. |
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| 42. |
- Scrivens, A, et al.
(author)
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Survey of transfusion practices in preterm infants in Europe
- 2023
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In: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 108:4, s. 360-366
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Journal article (peer-reviewed)abstract
- Preterm infants commonly receive red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusions. The aim of this Neonatal Transfusion Network survey was to describe current transfusion practices in Europe and to compare our findings to three recent randomised controlled trials to understand how clinical practice relates to the trial data.MethodsFrom October to December 2020, we performed an online survey among 597 neonatal intensive care units (NICUs) caring for infants with a gestational age (GA) of <32 weeks in 18 European countries.ResultsResponses from 343 NICUs (response rate: 57%) are presented and showed substantial variation in clinical practice. For RBC transfusions, 70% of NICUs transfused at thresholds above the restrictive thresholds tested in the recent trials and 22% below the restrictive thresholds. For platelet transfusions, 57% of NICUs transfused at platelet count thresholds above 25×109/L in non-bleeding infants of GA of <28 weeks, while the 25×109/L threshold was associated with a lower risk of harm in a recent trial. FFP transfusions were administered for coagulopathy without active bleeding in 39% and for hypotension in 25% of NICUs. Transfusion volume, duration and rate varied by factors up to several folds between NICUs.ConclusionsTransfusion thresholds and aspects of administration vary widely across European NICUs. In general, transfusion thresholds used tend to be more liberal compared with data from recent trials supporting the use of more restrictive thresholds. Further research is needed to identify the barriers and enablers to incorporation of recent trial findings into neonatal transfusion practice.
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| 43. |
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