This suggests that there is no significant antigenic difference between current SAT FMD vaccine strains and the circulating SAT serotypes. Therefore, the vaccines are still fit-purpose for the control FMD in the region. The study did not identify incursion of any new lineages/topotypes of FMD into the sampled southern African countries.Foot-and-mouth disease (FMD) virus (FMDv), like other ribonucleic acid (RNA) genome viruses, has a tendency to mutate rapidly. As such, available vaccines may not confer enough cross-protection against incursion of new lineages and sublineages. This paper is a retrospective study to determine the topotypes/lineages that caused previous FMD outbreaks in 6 southern African countries and the efficacy of the current vaccines to protect cattle against them. A total of 453 bovine epithelial tissue samples from 33 FMD outbreaks that occurred in these countries from 2014 to 2018 were investigated for the presence of FMDv. The genetic diversity of the identified Southern African Type (SAT)-FMD viruses was determined by comparing sequences from outbreaks and historical prototype sequences. Of the 453 samples investigated, 176 were positive for four FMDv serotypes. Out of the 176 FMD positive cases there were 105 SAT2 samples, 32 SAT1 samples, 21 SAT3 samples, and 18 serotype O samples. Phylogenetic analysis grouped the SATs VP1 gene sequences into previously observed topotypes in southern Africa. SAT1 viruses were from topotypes I and III, SAT2 viruses belonged to topotypes I, II, III, and IV, and SAT3 viruses were of topotypes I and II. Vaccine matching studies on the field FMDv isolates produced  Foot-and-mouth disease (FMD) is a contagious viral disease clinically characterized by lesions in the mouth and feet of cloven-hoofed animals; the disease affects more than 70 animal species –4. FMD hAphthovirus in the family Picornaviridae and is classified into seven distinguishable serotypes and their respective topotypes [in vitro assays such as virus neutralization test (VNT) [Syncerus caffer) which is attributable to the continued presence of these FMDv serotypes in the region [The causative agent of FMD is an opotypes , 15. Eacopotypes . Vaccinest (VNT)  and enzyst (VNT) , 18, 19.st (VNT) . Among tst (VNT) , 22; howst (VNT) , 24. In e region –27.Worldwide, FMD viruses are maintained in two continents, Asia and Africa; in South America all countries except Venezuela are free with vaccination . The virHistorically, FMD has been a scourge in the southern African region. An overview of the disease in the region over a 50-year period from 1931 to 1990 recorded a total of 350 epizootic outbreaks in some countries of southern Africa . During Most information about FMD outbreaks in southern Africa is outdated and underreported. In this publication, a retrospective study of FMD outbreaks which occurred between 2014 and 2018 in 6 southern African countries, namely, Botswana, Malawi, Mozambique, Namibia, Zambia, and Zimbabwe, is presented. This study aimed to update the currently available reports on FMD outbreaks in this region. Topotype identification and antigenic characterization for virus strain differentiation done in this study can also help facilitate selection of appropriate vaccines to control the disease outbreaks.Epithelial tissue samples were collected during active FMD outbreaks from cattle exhibiting clinical signs and lesions suggestive of infection with FMDv by veterinarians of the affected countries. Over the study period (2014–2018), a total of 453 cattle epithelial tissues were received from eleven southern African countries for confirmatory diagnosis of FMD at the OIE sub-Saharan African Regional Reference Laboratory for FMD (OIE-SSARRLFMD) based at Botswana Vaccine Institute (BVI). The samples were preserved in transport medium containing equal volumes of glycerol and phosphate-buffered saline at pH 7.2–7.6 with antibiotics –34. The Bovine epithelial tissue samples were processed for virus isolation and extraction of FMDv ribonucleic acid (RNA) as described in the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals . The pro3 Corning® cell culture flasks from Sigma Aldrich. Each flask was inoculated with 500 μl epithelial tissue suspension and thereafter incubated at 37°C for 1 hr in a Thermo Fisher Scientific CO2 incubator to allow the FMDv if any in the sample to infect the cells. Then cell culture medium (15 ml) was added to each cell culture and further incubated at 37°C for 48 hrs. FMD virus infected cells undergo degenerative changes, technically termed cytopathic effect (CPE). Such changes usually appear after 24 hrs but with very virulent virus strains they may appear as early as 12 hrs. After inoculation and incubation at 37°C, the cultures were examined microscopically daily using inverted light microscope  for evidence of CPE. If no CPE was observed after 48 hrs, the cultures were frozen at −70°C and then processed for second passage as described elsewhere [The procedure for FMDV isolation and typing as used by the RRLSSA-FMD has been well documented . Virus ilsewhere . If stillsewhere .μl of supernatant obtained from clarification of crushed clinical epithelial tissues. The ZR-Viral RNA kit™  was used for total RNA extraction following the user manual instruction with minor changes, the start volume of 200 μl instead of 100 μl, and 15 μl elution buffer instead of 50 μl [Total RNA was extracted from 200 of 50 μl .μl, OneTaq One-Step Enzyme Mix (25X) 2 μl, Gene-Specific Forward Primer (10 μM) 2 μl, Gene-Specific Reverse Primer (10 μM) 2 μl, and total RNA (1 μg) Xμl added in the RNA extraction room. RNA concentration was determined using the Qubit® 3.0 fluorimeter from Thermo Fisher Scientific. The final volume was made up to 50 μl using nuclease-free water. The Applied Biosystems® Veriti® 96-well thermal cycler  was used for RT-PCR using the following parameters: reverse-transcription (RT) at 48°C for 30 min/1 cycle; followed by initial denaturation at 94°C for 1 min/1 cycle, denaturation at 94°C for 15 s/40 cycles, annealing at 50°C for 30 s/40 cycles, and extension at 68°C for 1 min/40 cycles; and a final extension at 68°C for 5 min/1 cycle, and held at 4°C before agarose gel electrophoresis. A volume of 25 μl of PCR product was mixed with 10 μl gel loading dye (6X) from NEB and loaded onto respective wells on a 1.5% agarose gel stained with GelRedTM . The amplicon bands were visualized under UV light and correct size was determined from alignment with a 100 bp DNA molecular weight marker. The expected band sizes for primer pairs used were 1045 bp, 1279 bp, and 1034 bp for SAT1, SAT2, and SAT3, respectively, [Using prior knowledge of the sample serotypes from antigen ELISA, serotype specific primer pairs were used. The forward primers were different for each serotype and these were SAT1U-OS, SAT2-P1-1223F, and SAT3-1C559F. The reverse primer SAT 2B208R was used for SAT1, 2, and 3 as described by Knowles and colleagues . The priμl, 2 μl of 5X sequencing buffer was mixed with 4 μl BigDye® Terminator v3.1 Ready Reaction Mix and 1 μl of appropriate sequencing primer at a concentration of 10 μmol and target template (RT-PCR products of VP1 specific reactions) diluted to contain 5–20 ng complementary DNA (cDNA). The following sequencing thermocycling parameters were set in the Applied Biosystems® Veriti® 96-Well Thermal Cycler , with a heated lid at 105°C to curtail evaporation: 96°C for 1 min and 25 cycles of 96°C for 10 s, 50°C for 5 s and 60°C for 4 min. The sequence product was purified using BigDye XTerminator™ Purification Kit  following the manufacturers protocol, and for a 20 μl reaction volume the procedure was as follows: pulse-centrifuge the reaction plate, and then pipette 90 μl of Sam™ Solution into each plate well, followed by 20 μl of homogenised XTerminator™ solution. The plates were then sealed using a clear adhesive film and vortexed for 30 minutes after which the plate was pulse-centrifuged. The sequenced product was run on an Applied Biosystems® 3130xl Genetic Analyzer  using recommended run module as per instruction manual.Sequencing of the VP1 gene was performed according to a procedure already described elsewhere , 38. Brin = 17), SAT2 (n = 36) and SAT3 (n = 14), were obtained from the National Centre for Biotechnology Information (NCBI) database. VP1 sequences from representative outbreak samples received during the study period and vaccine strains were SAT1 n = 5, SAT2 n = 19, and SAT3 n = 5. These were combined with the prototype FMDV sequence to determine the ancestry of the outbreak strains. Multiple sequence alignment of the sequences was done using Clustal W [X [X. The evolutionary history was inferred by using the Maximum Likelihood method and Tamura-Nei model [Phylogenetic analysis was carried out as described by Knowles and colleagues  with somlustal W  imbeddedtal W [X . The alital W [X , in MEGAei model . A 1000 50) of the homologous vaccine virus strain and the same dose of the field virus isolate [The antigenic relationship of the field virus isolates to the vaccine strains was determined using the two-dimensional virus neutralization test (2dmVNT). The 2dmVNT was carried out using pools of bovine vaccinal serum and 100 tissue culture infecting dose  was calculated as described elsewhere [The antigenic similarity which symbolises the antigenic match between the homologous vaccine virus and the heterologous field virus isolate expressed in relationship coefficients  0.3 indicate that there are no significant antigenic differences between the field and vaccine virus. A potent vaccine containing the vaccine strain was likely to confer protection.r1-values less than (<) 0.3 indicate that there are significant antigenic differences between the field and vaccine virus. A high potent vaccine can sometimes still confer protection, but not always.r1-values of zero (0) are given when no neutralization of the field virus isolate was observed at 100 TCID50.A total of 33 FMD outbreaks in cattle were reported during 2014–2018 period in southern Africa. A total of 176 out of 453 bovine epithelial tissue suspensions (38.8%) cultured in primary lamb kidney cells produced cytopathic effect (CPE) suggestive of FMDv replication in the cells. The CPE was confirmed to be that of FMDv by antigen ELISA test using serotype specific rabbit antiserum.Out of the 176 positive samples, 32 were FMDv serotype SAT1, 106 were FMDv serotype SAT2, 21 were FMDv serotype SAT3, and 17 were FMDv serotype O. Overall, 159/176 of the outbreaks were caused by the SAT serotypes. The annual distribution of the FMD positive samples by serotype is shown in Genotyping of the FMDV VP1 sequences generated clustered the outbreak sequences with FMDs with their respective SAT serotypes. The outbreak FMD viruses represented SATs topotypes that had been isolated previously from the southern African region as shown in X.The evolutionary history was inferred by using the Maximum Likelihood method and Tamura-Nei model . The booThe phylogenetic analysis results shown in r1-values) of ≥0.3 indicating that the vaccine viruses were most likely going to confer protection against the heterologous field virus strains. Representative r1-values of the field virus strains analyzed in this study are shown in Antigenic strain identification by vaccine matching using the two-dimensional virus neutralization test (2dmVNT) gave relationship coefficients  collected from cattle exhibiting clinical FMD have demonstrated the presence of FMD virus (FMDv). During the period examined, a single outbreak was confirmed in a country hitherto free from FMD. This outbreak in cattle occurred in August 2016 in the Island of Mauritius; the disease outbreak was confirmed to be caused by FMDv serotype O which belonged to the Middle East South Asia (ME-SA) topotype; the disease was effectively controlled by vaccination [In this review, a total of 33 FMD outbreaks were sampled from seven southern African countries, Botswana, Malawi, Mauritius, Mozambique, Namibia, Zambia, and Zimbabwe. The causative viruses have been identified and characterized. Approximately 39% of the epithelial tissue samples n = 3 collectcination .n = 33), 30 out of 33 outbreaks were caused by FMD viruses in Pool 6  while 3 out of 33 outbreaks were caused by FMD viruses in Pool 4. Of the outbreaks caused by Pool 6 virus serotype SAT2 contributed 20 of the 30 reported outbreaks, SAT1 contributed 6 out of 30 reported outbreaks, and SAT3 was the least reported, contributing 4 out of 30 outbreaks. Sporadic reporting and limited sampling during outbreaks might have supported the problem of sampling bias, which leads to virulent strains with higher propensity for transmission being sampled more. This sampling bias might lead to the wrong perception that the sampled strains are the predominant ones in the field. Sampling bias could be solved by intermittent sampling during periods of low incidence [Out of these outbreaks  have given l to 0.3 . These rl to 0.3 . The VP1l to 0.3  demonstrThe resurgence of FMDV serotypes SAT3 and O in southern Africa resulted in some countries revisiting their vaccination strategies; Zambia now has to vaccinate against all the three serotypes in Pool 6 as well as against serotype O from Pool 4. Mozambique and Namibia now also use a trivalent vaccine  instead of the bivalent vaccine (SAT1 and SAT2) for the control of FMD. The burden of FMD control by vaccination in Zambia has therefore increased and they might not be able to prevent the spread of the exotic viruses (Pool 4) further south to Zimbabwe, Botswana, and Namibia. It is henceforth suggested that concerted efforts coordinated by SADC and backed by international donor agencies such as the FAO, World Bank, and/or the EU be launched as a matter or emergency to provide effective control and prevention of FMD associated with exotic viruses spreading into the region from eastern Africa.Elsewhere on the African continent, the control of FMD by vaccination is not regularly conducted. Many countries including those in southern Africa continue to vaccinate cattle in response to outbreaks rather than conducting regular prophylactic vaccinations of at least twice a year as the antibody decay after vaccination is approximately six months , 55. MosThe epidemiology of FMD in the African continent is complex and poorly understood; this constrains the ability to implement control strategies suitable for the continent . As suchA lot is known about the molecular epidemiology of FMD caused by SAT serotypes of FMDv in southern Africa , 27, 52.Foot-and-mouth disease continues to be a big constraint towards international trade of cloven-hoofed livestock for most countries in southern Africa and elsewhere where the international trade of cattle (beef) forms an integral part of the country's gross domestic product (GDP). In southern Africa, the main FMD virus strains circulating in the field in the order of dominance are SAT2 and SAT1; however SAT3 now constitutes a potentially big threat to Zambia and the countries that it closely borders with. The same trend in FMD distribution patterns was observed in 1995 by Thomson .Syncerus caffer), regular vaccination of cattle using trivalent FMD vaccine  be adopted to prevent the spread of these viruses to susceptible populations. In those countries where exotic FMDv serotypes have entered from countries of different FMDv Pools, the exotic serotypes should be included in the vaccination regimes. Countries in southern Africa and elsewhere in sub-Saharan Africa need to regularly submit FMD samples to OIE reference laboratories in order to monitor the FMD situation in the region and study any epidemiological shifts and antigenic variability of the circulating strains relative to the homologous strains used in vaccine manufacturing.It is recommended that in those countries where FMD control by vaccination is practiced, especially in areas where cattle, sheep, and goats share the same habitat with the African buffalo (


We revisit the problem of modeling the ocean’s contribution to rapid, non-tidal Earth rotation variations at periods of 2–120 days. Estimates of oceanic angular momentum  are drawn from a suite of established circulation models and new numerical simulations, whose finest configuration is on a  T of 2 to 150 days. This “sub-seasonal” end of the spectrum is unique in that relevant excitations arise from either atmosphere or ocean, in an approximate ratio of 2:1 for polar motion at The ocean stores and releases appreciable amounts of non-tidal angular momentum. Work around the turn of the millennium  assumptions of a rotationally symmetric Earth and complete core–mantle decoupling on sub-seasonal time scales; see Chen et al  used in this study are based on area integrals of mass loads, with atmospheric pressure  and cast the net freshwater flux into the ocean due to precipitation, evaporation, and continental run-off in an additional, barystatic sea-level angular momentum function  sign signv in in Eqs. , 2004. Act Ponte . The timf. Ponte . An ad hf. Ponte . EquivalThroughout the paper, we interchangeably use the terms “excitation function” and “angular momentum function” Eqs.  and 5 annent Eq. .Our analysis spans a full 5-year period 2007–2011), which allows for robust inferences about rapid ERP variability and renders our own simulations Sects. , 3.4 man, which aThe Earth System Modeling Group at GeoForschungsZentrum Potsdam . Note that Quinn et al (ECCO (Estimating the Circulation and the Climate of the Ocean) Version 4 Release 4 (ECCOv4 for short) is a global ocean state estimate derived using adjoint-based nonlinear inverse modeling .Two unconstrained MITgcm simulations were performed by us to assess the potential role of higher horizontal resolution for improving rapid OAM estimates. The first of these experiments, labeled LLC90, is based on the discrete ECCOv4 setup but uses first-guess  surface boundary conditions from ERA-Interim. The simulation was initialized from ECCOv4 climatologies for hydrographic variables and spun up for 6 months from a state of rest at 1 July 2006. Fifty layers of various thickness are used in the vertical, along with a nonlinear free surface and a time step of 30 min. Code and model parameters of the run slightly deviate from the ECCOv4 choices and are aligned with a hierarchy of LLC configurations derived from a global The setup for our eddy-permitting experiment, termed LLC540, is also part of the LLC suite and has a nominal horizontal resolution of nemenlis  for detanemenlis . In bothWe also consider results from a simple shallow-water model, referred to as DEBOT  values at entclass1pt{minimaHallberg . TransieHallberg , a proceA paramount feature in Fig. Table entclass1pt{minimass et al .Our assessment of oceanic effects contains several findings of value. First, geodesy’s leading OAM series given by MPIOM do not adequately reduce variance of the observed sub-seasonal polar motion excitation. Table entclass1pt{minimation Eq. .As a consistency check (not shown), we have computed proxy equatorial OAM motion terms from daily-averaged MPIOM bottom pressure fields , so we evaluate their sum against mentclass2pt{minima is Earth’s mean radius and Results above for the LLC simulations can be given additional context by mapping their differences in terms of all modes according to Eq.  analysis for vector quantities  of the variance in x OAM functions contain contributions from several other EOFs and are not discussed here.Panels a and b in Fig. mentclass2pt{minimA) and the Chile Rise (B) in the Bellingshausen Basin, i.e., areas known for their high levels of barotropic variability on intraseasonal time scales  to ocean models with higher horizontal resolution and more nuanced dissipation properties. In particular, excitation budgets in Sect. Further increases in spatial resolution will give rise to a more active mesoscale eddy field, which can substantially change bottom velocities and pathways of kinetic energy in general (Thoppil et al Pure forward models aside, the merits of higher resolution may also be explored in novel eddy-resolving (


To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population.w, and two-way mixed, single measures, consistency ICC  were determined. Adequate agreement was defined as κ/κw ≥ 0.80 and ICC ≥ 0.80 (significance level at 95% CI ≥ 0.65).Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens’ MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen’s κ (dichotomized data), Cohen’s κw and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists.Forty-nine subjects  with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen’s κ. All raters achieved adequate agreement expressed as Cohen’s κWe conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens’ MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences.Radiologists with varying experience achieve adequate inter-modality agreement with similar accuracy when Scheltens’ MTA scale is used to rate MTA on a non-demented population.• Differences in rating styles might affect accuracy, this was most evident for senior neuroradiologists, and only junior radiologists achieved adequate agreement on dichotomized  ratings.• The use of an MTA scale template might compensate for varying clinical experience which could make it applicable for clinical use.•  Medial temporal lobe atrophy is an important structural finding associated with Alzheimer’s disease but MTA can be found in preclinical dementia –5. In clA recent European survey showed that 75% of responding centers used VRS in clinical practice where white matter changes scales were regularly used by 82% and the MTA scale by 81%; other VRS were less common. Lack of training was the main reason for not using VRS in clinical practice . It has However, ratings have not been compared to a gold standard rating of MTA for assessment of accuracy and inter-modality agreement has not yet been assessed in a non-demented population with mild cognitive symptoms (MCS). We hypothesized that the use of an MTA template might reduce the effect of rating style differences and yield adequate agreement across radiologists with varying clinical experience. Our aims were therefore (1) to assess inter-modality agreement for MTA ratings in a non-demented population in order to mimic the everyday clinical situation and (2) to assess accuracy across radiologists with varying clinical experience, given access to an MTA scale template during ratings.https://biofinder.se). Eligible subjects were enrolled between the years 2010 and 2014, had a Mini-Mental State Examination score of 24 to 30, aged 60 to 80 years, and did not meet the criteria for dementia [This observational study was performed at a single center on a population recruited from the Swedish BioFINDER (Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably) study MCS cohort  and normal , consistent with our clinical routine but also to allow for comparison with previous studies –8.Four raters—one last year resident in radiology (“Rater 1”), one senior neuroradiologist with > 30 years’ experience (“Rater 2”), one radiologist on first year of a residency in neuroradiology (“Rater 3”), and one senior neuroradiologist with seven years’ experience (“Rater 4”)—performed ratings of all CT and MRI scans with 2 weeks apart. For group comparison, “Rater 1” and “Rater 3” are denoted “junior radiologists” and “Rater 2” and “Rater 4” are denoted “senior neuroradiologists.” All raters had access to an MTA template  during The MRI scans were performed on a 3-T  scanner where coronal T1-weighted three-dimensional magnetization prepared rapid acquisition with gradient echo, echo time 3 ms, repetition time 1950 ms, flip angle 9°, acquisition matrix 356 × 215, and pixel spacing 0.98/0.98 were obtained. The CT scans were performed on scanners from three different vendors with 120-kV voltage, 150 to 320-mAs exposure, 0.5 to 0.75 collimation, and 0.36 to 0.65 pitch factor. Only subjects where original 0.75-mm axial slices were available for reformatting in our PACS were eligible for inclusion. All scans were reformatted into oblique slices perpendicular to the hippocampi with 3-mm thickness and no gap. All images were assessed in our PACS where CT images were assessed with a center width of 40 HU and a window width of 80 HU.w) with quadratic weighting was estimated. For assessment of average agreement on ordinal data for several (> 2) raters, two-way mixed, single measure, consistency intraclass correlation coefficients (ICC) were estimated as a substitute for Cohen’s κw [p < 0.05 was considered significant. In order to assess accuracy, true positive rates (TPR) and true negative rates (TNR) were estimated for each radiologist with 95% CIs using MEDCALC®  online statistics calculator . Sample size was estimated in accordance with a confidence interval (CI) construction for κ-estimations suggested by Donner and Rotondi and performed using the “kappaSize” package in R [For assessment of inter-modality agreement on dichotomized data, Cohen’s κ was estimated. For assessment of inter-modality agreement on ordinal data, Cohen’s weighted κ  for all raters  for “Rater 1” and “Rater 3” (junior radiologists) but not for “Rater 2” and “Rater 4” (senior neuroradiologists). Inter-modality agreement on ordinal ratings expressed as Cohen’s κCompared to our gold standard, TPR varied from 77 to 100% on MRI and from 69 to 92% on CT. True negative rates varied from 94 to 100% on MRI and from 89 to 100% on CT. Junior radiologists performed somewhat better compared to senior neuroradiologists, but the differences were not significant based on visual comparison of 95% CIs  Sample size was considered sufficient for the κ-analysis; however, it is still relatively small which hampers the interpretation of TPR and TNR and over- and underestimation of MTA, respectively. (ii) We assessed a non-demented population with MCS which we believe better reflects the everyday clinical situation. This approach would raise concern if our intention had been to assess the diagnostic accuracy of the MTA scale, but since our aim was only to assess agreement, we considered our approach sufficient for this study. (iii) Visual ratings are subjective, and it would be preferable to use an automated rating as gold standard or at least compare human ratings to automated ratings for correlation and agreement. No automated ratings applicable on both CT and MRI and available for clinical use were known to us at the time of conceptualization and finalization of this study. We therefore chose a gold standard based on consensus ratings by two experienced neuroradiologists, but this approach could itself result in a potential bias. (iv) The retrospective recruitment of clinical CT exams resulted in scans being performed on different scanners. Although this is a reality in the everyday clinical situation, a potential bias from differences in image quality cannot be excluded. (v) We have not evaluated how raters would perform without access to a template or if proper training had preceded the ratings. However, knowledge of participation in a study where agreement is concerned could itself result in a hampering rater bias. Additionally, we have not assessed how raters at other institutions would perform under the same circumstances.We hypothesized that using an MTA template could reduce the effect of rating style differences and yield adequate agreement across radiologists with varying clinical experience. Our results showed that adequate inter-modality agreement, with no significant differences across radiologists, was achieved when an MTA template was used. Using a template might thus compensate for varying experience and rating style differences. We believe our results further strengthen the already endorsed use of the MTA scale in clinical practice –9, 11.In summary we conclude that radiologists with varying clinical experience achieve adequate inter-modality agreement with similar accuracy when Scheltens’ MTA scale is used to rate MTA on a non-demented population. However, TPR varied between raters which could be attributed to rating style differences.


Our data thus provide evidence that combustion of sedimentary organic matter by igneous intrusions and/or wildfires played a significant role in the environmental perturbations accompanying the event. This process has a modern analog in anthropogenic combustion of fossil fuels from crustal reservoirs.The sources of isotopically light carbon released during the end-Triassic mass extinction remain in debate. Here, we use mercury (Hg) concentrations and isotopes from a pelagic Triassic–Jurassic boundary section  to track changes in Hg cycling. Because of its location in the central Panthalassa, far from terrigenous runoff, Hg enrichments at Katsuyama record atmospheric Hg deposition. These enrichments are characterized by negative mass independent fractionation (MIF) of odd Hg isotopes, providing evidence of their derivation from terrestrial organic-rich sediments (Δ Mercury (Hg) concentrations and isotopes from a deep-ocean Triassic–Jurassic (~201 Ma) boundary section provide evidence of large inputs from terrestrial organic-rich sources through combustion by magmatic sills and wildfires. These consequences are believed to have been driven by rising atmospheric CO2 levels, which have been linked to the emplacement of the Central Atlantic Magmatic Providence (CAMP). Although the magnitude of the CO2 rise (~2–4×) during the T–J transition has been estimated by plant stomatal ratios as well as pedogenic carbonate isotopes6, debate continues regarding the source(s) of excess CO2, with proposals of mantle-derived CO27, heating and devolatilization of organic-rich and carbonate-bearing sedimentary rocks8, and release of methane from permafrost or marine clathrates9. These hypotheses are partly motivated and supported by the negative carbon isotope excursions (CIEs) observed in both organic and inorganic records of the T–J transition. For example, a direct link between the CAMP and CO2 release from organic-rich sediments in Brazilian basins was recently inferred by Heimdal et al.8 based on carbon-cycle modeling combined with radiometric dating constraints. However, the negative CIE of the T–J transition ranges in magnitude from <1‰ to ~8‰ in different settings, suggesting that biological and chemical processes, preservation, as well as sedimentation rates imparted a large local overprint on the global signal10, which complicates analysis of the magnitude of CAMP emissions based on carbon-cycle mass-balance calculations11.Global environmental and biotic perturbations, including extreme warming, ocean acidification and anoxia, and a mass extinction, characterize the Triassic–Jurassic (T–J) transition (~201 Ma)12, Supplementary Notes 13  of odd isotopes , yield characteristic values in different reservoirs, facilitating their use as a Hg provenance proxy16 (Supplementary Note 199Hg) are largely unaffected by physical, chemical, and biological processes other than photo-reduction16. Reservoir-specific MIF values can be used to interpret Hg sources because Δ199Hg values are near-zero for direct volcanic emissions from the deep Earth, distinguishing them from terrestrial and atmospheric fluxes, which generally show negative and positive Δ199Hg values, respectively16 (Supplementary Note Mercury (Hg) concentrations and isotope ratios in sediments are widely used as a proxy for volcanic activity in stratigraphic successions , and the atmosphere22. Although processes of removal of Hg from pelagic seawater are complex24, analysis of a pelagic open-ocean section far from continental influences is needed to gain a better understanding of atmospheric Hg fluxes during the T–J transition15.Sedimentary Hg concentrations and isotopes around the T–J transition have previously been investigated in various marine, near-coastal and terrestrial settings Fig. . Both ma25, increasing the potential for recovering a CAMP signal. Furthermore, owing to slow rates of pelagic sedimentation at abyssal water depths, the study section has the potential to yield a more globally integrated signal of atmospheric Hg transport than most other T–J transitional sections analyzed to date. Finally, the location of the study site antipodally to the CAMP allows an assessment of the areal extent of CAMP volcanic influences.In this study, we present Hg concentration and isotope data (Supplementary Data 199Hg) shows slightly positive values (0 to +0.11‰) within the background intervals and slightly negative values (−0.14 to −0.05‰) within the extinction interval  exhibits near-zero values within the background intervals and slightly negative values (−0.08 to 0.06‰) within the extinction interval  in the background intervals below and above the T–J extinction interval (−3.2 m to −2.0 m) but rise to >60 ppb (max 163 ppb) within it Fig. . Total oval Fig. . Mass inval Fig. .Fig. 2Ch27  could also be produced through mixing of multiple Hg sources, e.g., a combination of terrestrial (negative Δ199Hg) and atmospheric (positive Δ199Hg) inputs22. Mercury data from a remote pelagic setting such as Katsuyama permit the global atmospheric signal to be isolated more effectively.Mercury has been used in T–J transitional research to track mantle-derived volcanic inputs to continental as well as shallow- to intermediate-depth marine sections proximal to the Pangean supercontinent27 Fig. . Near-ze30, e.g., sedimentation rates, redox conditions, or specific host minerals , limiting its redistribution within the ocean system32 , are a promising tool for tracking Hg sources to sediments  is associated with T–J transitional beds containing excess Hg, indicating a shift in the source(s) of Hg relative to the background flux (Δ199Hg > 0‰)  species and positive Δ199Hg in the oxidized Hg(II) species34. For this reason, terrestrial Hg pools normally show negative Δ199Hg due to the uptake of gaseous Hg(0)36. On the other hand, atmospheric Hg(II) is soluble and easily scavenged from the atmosphere through rainfall37, resulting in oceanic Hg pools  showing positive Δ199Hg due to wet deposition of Hg38  Figs. , 3. Merc199Hg values that were assumed to record volcanic release of deep-mantle Hg17, although an alternative is mixing of atmospheric (positive MIF) and terrestrial (negative MIF) Hg sources. At Levanto18, T–J transitional strata record only a slight decrease of Δ199Hg relative to the background flux (which was dominantly derived from seawater), rendering distinction of volcanic, atmospheric, and terrestrial sources difficult. At the epicontinental St. Audrie’s Bay site18, background Hg fluxes were dominantly of terrestrial origin (Δ199Hg −0.4‰ to −0.2‰), but rising Δ199Hg within the extinction interval (−0.17‰ to −0.07‰) resulted from either dominantly atmospheric deposition (Δ199Hg −0.17‰ to −0.07‰) or a mixture of atmospheric and terrestrial sources that were weighted toward the former. For the two terrestrial settings (Haojiagou and Qilixia)19, the relatively higher Δ199Hg values near the extinction interval  than that during the background interval  document mixing of terrestrial and atmosphere sources.Interpretation of Hg isotope signals in continental shelf settings is complicated by the influence of riverine terrestrial inputs. At Nevada, T–J transitional strata exhibit near-zero Δ199Hg values (ca. −0.14‰) associated with Hg spikes in the T–J extinction interval of the Katsuyama section have several potential sources, including photoreduction of Hg (II) complexed by reduced sulfur ligands in a euxinic photic zone, terrestrial inputs by soil erosion, and heating of organic matter in soils and sedimentary rocks  through wildfires and/or contact metamorphism of organic-rich sedimentary rocks by igneous sills was the main source of low-MIF Hg.The negative Δ ca. −0.1‰ associacks Fig.  and redo42, because plants have a strong ability to accumulate gaseous Hg(0) through stomata, as shown by negative Δ199Hg values in plant tissues43. Soil could accumulate a substantial amount of Hg from vegetation13. For this reason, terrestrial materials  are commonly characterized by elevated Hg concentrations44 and negative Δ199Hg values  in the near-coastal, shallow-marine St. Audrie’s Bay18 and terrestrial Hajiagou19 successions near the T–J transition are in agreement with results from similar present-day settings16  in the atmosphere can alter the isotopic signature of volcanic-Hg (Δ199Hg near zero), resulting in negative Δ199Hg values in the gaseous Hg(0) pool and positive Δ199Hg values in the aqueous Hg(II) species. Gaseous Hg(0) with negative Δ199Hg that is taken up by land plants through their stomata can be subsequently released by wildfire combustion. However, this source is unlikely to have been important during the CAMP eruptions as pelagic sediments would have recorded Δ199Hg values ranging only from near-zero (volcanic Hg inputs) to negative (wildfire-released Hg).In the modern, wildfire combustion of  vegetation and soil carbon is a major source of Hg to the atmosphere199Hg values to the atmosphere is the subsurface combustion of organic matter in coal and other organic-rich sedimentary rocks   in Brazilian basins49 such as the Amazonas and Solimões, in which organic-rich sediments of the Barreirinha, Jandiatuba, Jaraqui and Ueré formations contain up to 8% TOC50. Heating of these formations by CAMP intrusives may have been a major contributor to elevated atmospheric CO2 concentrations and the negative CIE through the T–J extinction interval51. Although Hg concentrations have not been reported for these organic-rich formations to date, Hg is generally about one order of magnitude higher in coals and black shales compared to other sedimentary rock types44. Contact metamorphism of organic-rich sediments, especially those containing abundant terrestrially derived organics, should therefore emit Hg exhibiting low MIF, potentially accounting for negative Δ199Hg values in the T–J extinction interval at Katsuyama  Fig. . CAMP ig200Hg  to Hg (II)54. Terrestrial soil erosion and volcanic emissions of mantle-sourced mercury cannot explain the coupled negative Δ199Hg and Δ200Hg excursions at Katsuyama because both of these sources are characterized by Δ200Hg of ~0‰55. In contrast, vegetation (and organic-rich sediments derived therefrom) tend to show coupled negative Δ199Hg and Δ200Hg due to foliage uptake of Hg(0) from the atmosphere45.Further support for the hypothesis of mobilization of Hg from an organic-rich sedimentary source followed by atmospheric transport during the T–J transition is provided by negative excursions of Δ0Hg Fig. . MIF of 57. Much evidence now supports the role of combustion of organic matter by intrusives  and wildfires  as significant sources of Hg and carbon to the surface Earth during mass extinctions at the Permian–Triassic20 and Triassic–Jurassic8 boundaries. Combustion of fossil fuels was the largest source of carbon to the Earth’s surface during 1850-2019, with cumulative emissions of 445 ± 20 GtC (gigatons of carbon)58. The average release rate was ~2.6 GtC yr−1 over that interval, or one order of magnitude greater than the rate of release of carbon during the T–J transition (~0.21 GtC yr−1)8. Thus, although it is hard to know the eruptive rates of CAMP, the amount and rate of release of greenhouse gases  by modern mining and fossil fuel burning are larger than LIP-related perturbations in deep time, reflecting the seriousness of present-day anthropogenic emissions and their implications for the future climate state of the Earth.Heating of vegetation and soil in surface as well as organic-rich sediments  in the subsurface represents a potentially larger Hg flux to the atmosphere than direct volcanic Hg release from the deep Earth. Sediments containing abundant volatiles such as Hg, carbon, sulfur, and halogens are likely to play a significant role in environmental and biotic perturbationsIn this work, elevated Hg concentrations within the Triassic–Jurassic transition of a pelagic section from the central Panthalassic Ocean provide evidence of excess Hg inputs via atmospheric loading. Negative MIF values associated with these Hg enrichments support an inference of thermogenic Hg generated through volatilization of organic matter in sedimentary rocks heated by CAMP-related igneous sills and/or in soils by wildfires. These processes are likely to have released large amounts of toxic gases that were harmful to the contemporaneous environment and biosphere. The release of Hg by heating of organic-rich sediments  is a significant factor in present-day biotic and environmental perturbations of the Earth-surface system.59. Our study section is part of the Mino Terrane, which runs from SW to NE across central Honshu. This accretionary complex is composed of late Paleozoic through Mesozoic igneous rocks, limestones, siliciclastic rocks, and bedded radiolarian cherts60. The cherts represent low-latitude pelagic deposits that accumulated below the oceanic calcite compensation depth62. The bedding of the sediments, which reflects variable chert content, was likely produced by variations in the sinking flux of siliceous radiolarian tests as well as climate-driven changes in the delivery of windblown silt and clay components65.The Mino-Tamba terrane complex, running through central Japan, is one of the largest surviving areas of pelagic sedimentation from prior to the Jurassic Period. These sediments, which were deposited several thousand kilometers from major sources of detrital sediment, accumulated at extremely low sedimentation rates and preserve a time-integrated signal of open-ocean conditions64. Beds dip nearly vertically and are deformed by a complex system of faults and tight folds mapped in detail by Fujisaki et al.66. The data presented in this study come from a single coherent structural block bounded by the F4 and F9 faults . The section is composed of bedded cherts, with individual cherts beds ranging in thickness from 1 to 10 cm, with most beds being <4 cm in thickness. The beds are separated by millimeter-scale shale partings and are generally red in color. There is no major facies change in the Katsuyama section across the Triassic–Jurassic boundary, though minor changes in the color of the chert may reflect variation in depositional conditionsHaeckelicyrtium breviora and Globolaxtorum tozeri radiolarian assemblages as well as the Misikella posthernsteini conodont Zone40. The Triassic–Jurassic boundary (−2.2 m) in the Katsuyama section was located based on the transition from the Globolaxtorum tozeri radiolarian Zone to the Pantanellium tanuense Zone59. This placement is supported by the LAD of the conodont Misikella posthernsteini62 and coincides with a noticeable change in the color of the chert66. The overlying Lower Jurassic beds (−2.2 m to 2.4 m) are assigned to the Parahsuum tanuense Zone68 and exhibit a noticeable transition from predominantly red to predominantly gray cherts in the middle of Subzone III, indicating a Hettangian to Sinemurian (Early Jurassic) age for the change in environmental conditions66.The lowermost beds of our measured section are ~3 meters (−5.1 m to −2.2 m) below the T–J boundary and are likely Rhaetian (latest Triassic) in age, based on the occurrence of the n = 157) were analyzed using a Direct Mercury Analyzer (DMA80) at Yale University. About 150 mg for chert samples were used in this analysis. Results were calibrated to the Marine Sediment Reference Material MESS-3 (80 ppb Hg). One replicate sample and a standard were analyzed for every ten samples. Data quality was monitored via multiple analyses of MESS-3, yielding an analytical precision (2σ) of ±0.5% of reported Hg concentrations.Samples were trimmed to remove visible veins and weathered surfaces and pulverized to ~200 mesh in an agate mortar for geochemical analysis. Aliquots of each sample were prepared for various analytical procedures. Hg concentrations (n = 259) were measured using an Eltra 2000 C–S analyzer at the University of Cincinnati. Data quality was monitored via multiple analyses of the USGS SDO-1 standard with an analytical precision (2σ) of ±2.5% of reported values for carbon and ±5% for sulfur. An aliquot of each sample was digested in 2 N HCl at 50 °C for 12 h to dissolve carbonate minerals, and the residue was analyzed for total organic carbon (TOC), with total inorganic carbon (TIC) obtained by difference.Carbon and sulfur concentrations (n = 61) were measured by Agilent 7500a inductively coupled plasma mass spectrometry (ICP-MS) at the State Key Laboratory of Geological Processes and Mineral Resources, China University of Geosciences (Wuhan). About 50 mg of each sample powder were weighed into a Teflon bomb and then moistened with a few drops of ultra-pure water before addition of 1 mL HNO3 and 1 mL HF. The sealed bomb was heated at 190 °C in an oven for more than 48 h. After cooling, the bomb was opened and evaporated at 115 °C to incipient dryness, then 1 mL HNO3 was added and the sample was dried again. The resultant salt was re-dissolved with 3 mL 30% HNO3 before it was again sealed and heated in the bomb at 190 °C for 12 h. The final solution was transferred to a polyethylene bottle and diluted in 2% HNO3 to about 80 mL for ICP-MS analysis. Analysis of the international rock standards BHVO-2 and BCR-2 yielded an analytical precision better than 5%, according to the relative standard deviation (RSD).Trace element abundances (n = 14) was analyzed for Hg isotopes at the State Key Laboratory of Ore Deposit Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang. A double-stage tube furnace coupled with 40% anti aqua regia  trapping solutions was used for Hg preconcentration, prior to isotope analysis69. All the solutions were diluted to ~0.5 ng mL−1 Hg in 10–20% (v/v) acids using 18.2 MΩ cm water, and analyzed by Neptune Plus multiple collector inductively coupled plasma mass spectrometer . The instrument was equipped with the HGX-200 system and an Aridus II Desolvating Nebulizer System  for Hg and Tl introduction, respectively. NIST SRM 997 Tl standard (50 ng mL−1) was used as an internal standard for simultaneous instrumental mass bias correction of Hg. The instrument was tuned using the NIST SRM 3133 Hg standard solution for maximum intensity of 202Hg signal using Ar gas flows, torch position, and lenses.A subset of samples (xxxHg), were calculated as the difference between measured δxxxHg and the theoretically predicted δxxxHg value, in units of per mille (‰), as follows:199Hg and 200Hg, respectively70. NIST-3177 secondary standard solutions, diluted to 0.5 ng/mL Hg with 10% HCl, were measured every 10 samples. Standard reference material GSS-4 (soil) was prepared and measured in the same way as the samples. Analytical uncertainty was estimated based on replicate analyses of the NIST-3177 secondary standard solution and full procedural analyses of GSS-4.Hg isotopic results are expressed as delta (δ) values in units of per mille (‰) variation relative to the bracketed NIST 3133 Hg standard, as follows:Supplementary InformationDescription of Additional Supplementary FilesSupplementary Data 1Peer Review File


This allows us to benefit from the well-established read-out methods of ferromagnets, while the essential advantages of antiferromagnetic spintronics are only slightly diminished. We show one-to-one imprinting of the antiferromagnetic on the ferromagnetic domain pattern. Conversely, alignment of the Permalloy magnetization reorients the Mn2Au Néel vector, an effect, which can be restricted to large magnetic fields by tuning the ferromagnetic layer thickness. To understand the origin of the strong coupling, we carry out high resolution electron microscopy imaging and we find that our growth yields an interface with a well-defined morphology that leads to the strong exchange coupling.In antiferromagnetic spintronics, the read-out of the staggered magnetization or Néel vector is the key obstacle to harnessing the ultra-fast dynamics and stability of antiferromagnets for novel devices. Here, we demonstrate strong exchange coupling of Mn Antiferromagnets offer faster operation speed and immunity to stray fields, however, readout of the Neel vector is difficult. Here, Bommanaboyena et al present a heterostructure of a ferromagnet and antiferromagnet, combining easy readout with the benefits of antiferromagnetic spintronics. N, typically along one out of two perpendicular easy axes4. The major benefits of using AFMs as active elements in spintronics are their intrinsically fast THz dynamics5 and their stability against external magnetic fields, e.g., up to 30 T in the case of Mn2Au6.A basic concept of antiferromagnetic (AFM) spintronics is to store information by the alignment of the staggered magnetization or Néel vector 9 or for metallic compounds in the bulk of the AFM itself10. In the latter case, only CuMnAs and Mn2Au have been identified to combine the required crystallographic and magnetic structure with strong spin-orbit coupling, such that a current along a specific direction can create a bulk Néel spin-orbit torque (NSOT) acting on the Néel vector10. Indeed, for both compounds, current pulse-induced magnetoresistance effects of the order of 1% and below were observed and associated with a rotation of the Néel vector15. Furthermore, the current pulse-induced reorientation of the Néel vector of CuMnAs(001) and Mn2Au(001) was directly demonstrated by magnetic microscopy17. From these only two available compounds with a bulk NSOT, Mn2Au stands out concerning potential memory applications due to its metallic conductivity, high Néel temperature (>1000 K)18, and magnetocrystalline anisotropy, which results in a long term room temperature stability of Néel vector aligned states6.Regarding the manipulation of the Néel vector orientation, the application of short current pulses creating spin-orbit torques (SOT) is a promising approach. These can be created at interfaces with heavy metal layersN of metallic antiferromagnets amounts to only 0.1–1%22. The spin-Hall magnetoresistance, most often utilized for insulating AFMs, is even smaller9. However, most applications require magnetoresistance (MR) effects above 20%23.Having established current-induced writing, still, the read-out of the Néel vector orientation in a potential device poses a major challenge. The magnitude of the anisotropic magnetoresistance effects (AMR) associated with the reorientation of 25. Thus, coupling AFM layers to thin FM films enabling e.g., TMR-based read-out is highly desirable, provided that the fast dynamics of the AFM, as well as its resistance against disturbing magnetic fields, is only moderately diminished. The former requires sufficiently strong coupling forcing the magnetization to follow the Néel vector, the latter is obtained by using very thin FM layers as we show in this work. Additionally, the sensitivity to external fields could be further reduced by replacing the single FM layer by a synthetic antiferromagnetically coupled FM bilayer with zero net magnetization26.In contrast to the case of AFM spintronics, such MR values are easily obtained in ferromagnetic (FM) spintronics, e.g., based on tunnel magnetoresistance (TMR) of FM/MgO/FM junctions2Au(001) epitaxial thin films with very thin (down to 2 nm) Permalloy (Py) layers. The coupling of the magnetization vector MF of the FM and of N results in the perfect imprinting of the AFM domain pattern of the Mn2Au film on the FM domain pattern of the soft Py layer. Similar imprinting was only reported for insulating AFM/ metallic FM bilayers such as 1.2 nm of Co on 40 nm of LaFeO327 or Fe(5 nm) on NiO (15 nm)28. However, in these cases, it was associated with a coercive field of only ≃100 Oe. In contrast, we show that 5000 Oe are required to reverse the magnetization of 2 nm of Py on 40 nm of Mn2Au(001). This, at room temperature, represents a coercive field corresponding to a field stability range, which is more than an order of magnitude larger than that in related CuMnAs/Fe(2 nm) bilayers, where a long term stable remanent magnetization was reported measuring at 200 K29. We show that in Mn2Au(001)/Py even at the coercive field of 5000 Oe MF and N do not decouple, but rotate together driven by the Zeeman energy of the FM layer. Thus, Mn2Au(001)/Py represents an excellent system for read-out in AFM spintronics. Furthermore, we identify the morphological origin of the exceptionally strong magnetic coupling between these AFM and FM layers.Here, we demonstrate a strong exchange coupling of 40-nm-thick Mn2Au has a tetragonal crystal structure and orders antiferromagnetically well above 1000 K18. It shows collinear AFM order consisting of antiparallel stacked planes with FM order, as indicated in Fig. 2Au(001) thin films in the formation of AFM domains with a typical size of 1 μm corresponding to all four associated orientations of N6.Mn2Au(001)(40 nm)/Ni80Fe20 (Py) (2 to 10 nm) bilayers, which are grown on Al2O3(r-plane) substrates with a Ta(001)-buffer layer and a capping layer of 2 nm of SiNx. Scanning transmission electron microscopy with high-angle annular dark-field imaging (STEM-HAADF) of the complete multilayer is shown in Fig. 2Au(001) thin film region  and Py, where we find that our growth leads to a defined Au termination of the AFM thin film. This is supported by UHV STM-images of a pristine Mn2Au surface, which show atomically flat terraces with steps corresponding to the half or the full length of the c-axis /N2Au00(40 nm)/N2Au00(40 nm)/N2Au00(40 nm)/N2Au(001) and Py layers by measuring magnetic hysteresis loops. Single Py films are in general magnetically soft with coercive fields of the order of a few Oe, which, as we will show below, drastically increases if they are coupled to AFM Mn2Au films.We quantified the coupling between the Mn2Au(40 nm)/Py(4 nm) bilayer measured in a superconducting quantum interference device (SQUID) with the easy [110] axis of the Mn2Au(001) thin film aligned parallel to the magnetic field direction.Figure 2Au, which either remains unaffected by the magnetic field or restores the original domain configuration when the field is zero again.After the as-grown sample consisting of an AFM multidomain state was placed in the SQUID, subsequent hysteresis loops with increasing maximum fields from 300 to 1000 Oe were measured as shown in the left inset of Fig. Hc ≃ 1600 Oe were obtained, as shown in Fig. MF and N, which results in the Zeeman energy of the FM layer driving a reorientation of N. Measuring hysteresis loops of Mn2Au(40 nm)/Py bilayers with various Py thicknesses varying from 2 to 10 nm, we observed linear scaling of the coercive field Hc with the inverse saturation magnetic moment 1/mF, as shown in the right inset of Fig. MF ⋅ H of the Py layer sets the remanent reorientation of both MF and N.However, once the magnetic field exceeds a threshold value, square-shaped easy axis loops with a coercive field To check if this holds, we next probe the orientation of the magnetization and the Néel vector:N and MF of a Mn2Au(40 nm)/Py(4 nm)/ SiNx(2 nm) sample by x-ray absorption spectroscopy (XAS), in the surface-sensitive total electron yield (TEY) as well as in the bulk sensitive substrate fluorescence yield (FY) mode. The magnetic contrast was obtained based on the x-ray magnetic linear and circular dichroism (XMLD/XMCD) effects, as described in the Methods section  parallel to the x-axis, i.e., to the easy [110]-direction of Mn2Au(001) and subsequently reduce the field to zero again. In agreement with the hysteresis loops discussed above, this results in a significant Ni-L2,3 edge XMCD signal (measured at a tilt angle of Θ = 60∘) showing a sizable remanent in-plane magnetization of Py  are shown in Fig. N becomes aligned parallel to MF as deduced by comparison with previous results30. After applying the magnetic field parallel to the 2Au(001) and subsequently reducing the field to zero, the XMCD (Θ = 60∘) becomes zero since the remanent magnetization is oriented perpendicular to the direction of photon incidence. Consistently, the XMLD signal (Θ = 0∘) is inverted both at the interface and in the bulk as expected for a 90∘ rotated Néel vector.In the as-grown state of the sample, due to the relatively large diameter of the x-ray beam (≃500 μm), we average over many AFM/FM domains canceling both the XMLD and XMCD to zero. We then apply a magnetic field of 1 T .With this strong parallel coupling of 2Au(001) layer of a Mn2Au(40 nm)/Py(4 nm)/SiNx(2 nm) sample was performed with a perpendicular incidence of the photon beam, as described in the Methods section.XMLD-photoelectron emission microscopy (PEEM) of the FM domain pattern of the Py layer and simultaneously of the AFM domain pattern of the Mn2Au(001) is perfectly imprinted on the FM domain pattern of the Py layer. Note that we have chosen also the FM XMLD contrast mechanism. As a result, also for the FM domains, only the axis along which MF is aligned produces a brightness contrast, not its direction, allowing for a direct comparison.We first discuss samples in the as-grown state, which were not exposed to a magnetic field. As shown in Fig. 2Au(001) layer as discussed above, crossing a morphological step at the interface does not change the AFM sub-lattice to which the MF of Py couples. This enables a strong planar exchange coupling at the interface, as indicated in Fig. The size of the AFM/FM domains of ≃1 μm, is at least one order of magnitude larger than the typical distance between the steps at the surface shown in Fig. 2Au AFM domains using scanning electron microscopy with polarization analysis (SEMPA)31 31 Fig. c–e. Hori)31 Fig. c and ver)31 Fig. d in-plan MF Fig. e. Furthe2Au(40 nm)/Py(4 nm)/ SiNx(2 nm) samples, which were previously exposed to magnetic fields above Hc  thin films forms during growth driven by an intrinsic mechanism such as the minimization of elastic energy32 and couples to the Py magnetization during the room temperature deposition of this thin layer. No exchange bias is present or obtainable in the bilayers investigated here, because of the high Néel temperature >1000 K of Mn2Au18, which prevents the creation of exchange bias by standard field cooling procedures33.The initial AFM domain pattern of the 40 nm Mn2Au/Py bilayers, the physics of exchange bias systems34 is a good starting point. Such systems can be used as references for the magnitude of the coupling of the Py magnetization MF to the Néel vector N of Mn2Au(001): The coercive fields presented above are at least one order of magnitude larger than those of typical exchange bias systems with a comparable Py-layer thickness38. Regarding other work on Mn2Au/FM bilayers, coercive fields of the order of only 100 Oe or less were reported, which could be related to different growth directions of these Mn2Au thin film40 as well as to the selection of Fe as the FM layer39, or do a different morphology.Nevertheless, for a discussion of the magnetic coupling mechanism of the Mn45, a planar exchange interaction at the AFM-FM interface is able to couple the Néel and magnetization vectors of the respective layers much more strongly46. This necessarily requires ferromagnetically ordered atomic layers of one defined AFM sub-lattice forming the surface of the AFM. Nevertheless, just the appropriate type of magnetic ordering is not sufficient, as depending on the interface morphology atomic steps can result in an alternating sign of the exchange coupling if different sub-lattices are present at the AFM/FM interface.An explanation for the substantially different coercive fields is obtained by considering the morphology of the interface between the AFM and FM layers. Whereas in the general framework of exchange bias, typically interface irregularities of the AFM such as roughness or random alloy effects associated with uncompensated spins are discussed as pinning centers for FM domain walls2Au(001)/Py bilayers leads to a well-defined Au termination of the surface of the Mn2Au(001) thin films  thin film on the FM domain structure of the Py layer, which by itself would be magnetically highly isotropic and soft.However, we find that our growth of the Mn2Au00/Py bilayMF to the Néel vector N is so strong that the layers are not even decoupled at the large coercive field but jointly rotated. We describe this reorientation under the action of the magnetic field using a macrospin model. Within this model, we describe the density of the magnetic energy per unit area of the Mn2Au/Py bilayer by2Au , and the second term describes the exchange coupling of the Néel and Py magnetization vectors. tAF and tF are the thicknesses of the antiferromagnetic and ferromagnetic layers, Jcoup > 0, and ξ describe the strength and the characteristic length of the exchange coupling between the AFM and FM layers. The third term represents the Zeeman energy of the Py layer in a magnetic field H. The coordinate axes x and y are aligned along the easy magnetic axes of Mn2Au.The coupling of the Py magnetization MF and N. In zero field MF↑↑N are both parallel to MF↑↑H, MF↑↓H, and MF⊥H and creates a ponderomotive force ∝ BMF, which acts on the domain walls47. This force shifts the domain walls thus reducing the fraction of the energetically unfavorable states (domains). This process shows up in the smooth growth of the magnetization as shown in Fig. The equilibrium configurations are obtained by minimizing  with resentclass1pt{minimaMF↑↑H and MF↑↓H. From the stability conditions for these states we obtain the coercive fieldHowever, above a threshold field value, the sample develops a single domain state and further cycling of the magnetic field induces switching between the states JcoupMFξ ≫ HantAF, the coercive field Hcoer → 4HanMstAF/(MFtF) is associated with the magnetocrystalline anisotropy of the Mn2Au layer and shows a linear dependence on the inverse magnetization 1/mF = 1/(MFtF) as observed experimentally . This is in good agreement with our previous estimation of K4 > 1 μeV/f.u.6, thereby supporting the validity of our model assumptions.Inserting the experimentally determined magnetization of the Py layers of Hcoer should also increase with the thickness tAF of the Mn2Au layer, which we indeed observed experimentally /Py(4 nm)). However, this increase is not linear, presumably due to a thickness dependence of the crystallographic order.N of the metallic antiferromagnet Mn2Au and the magnetization MF of ferromagnetic Py thin films. This results in the perfect imprinting of the AFM domain patterns of 40 nm Mn2Au(001) thin films on the FM domain pattern of thin (2–10 nm) Py layers, while maintaining high stability in external magnetic fields. The strong coupling results from the particular morphology that we obtain from our growth at the Mn2Au/Py interface, identified by TEM and STM, where within every domain always the same AFM sub-lattice couples to the FM thus maximizing the exchange coupling. This strong coupling of N and MF enables the electric detection of the Néel vector orientation via standard techniques used for ferromagnetic thin films, thereby providing a solution for the challenging read-out in antiferromagnetic spintronics.In summary, we demonstrated an extremely strong exchange coupling between the Néel vector 2O3(r-plane)/Ta(001)(13 nm)/Mn2Au(001)(40 nm)/Ni80Fe20 (Py)(2 to 10 nm)/SiNx(2 nm) samples were prepared by rf sputtering. The epitaxial Ta(001) buffer layers were sputtered with a substrate temperature of 700 ∘C, the epitaxial Mn2Au(001) thin films were deposited at 500 ∘C followed by an annealing procedure at 700 ∘C as described in refs. 49. All other layers are polycrystalline and were deposited at room temperature. SiNx(2 nm) sputtered from a Si3N4 target in Ar provides a very effective capping layer, which prevents sample oxidation while being highly transparent for photoemitted electrons50.All layers of the AlThe magnetic hysteresis loops of the samples were measured in a Quantum Design MPMS SQUID-magnetometer.2Au causes an x-ray magnetic linear dichroism (XMLD), i.e., an asymmetry in the absorption of linear polarized x-rays at the Mn-L2,3-edge for the polarization direction parallel and perpendicular to N30. It is sensitive to the components of N, which are parallel versus perpendicular to the electric field vector of the x-ray beam, but it does not change sign upon reversal of N. Thus we were able to investigate the orientation of N of a Mn2Au(40 nm)/Py(4 nm)/SiNx(2 nm) sample by x-ray absorption spectroscopy (XAS) at the I06 branch line at Diamond Light Source, which is equipped with a superconducting vector magnet. In parallel to probing the Néel vector orientation by XMLD, we were also able to probe the orientation of the magnetization of the Py layer using the x-ray circular dichroism (XMCD) at the Ni-L2,3 edge. The XMCD is an asymmetry in the absorption of circular polarized x-rays determined by the component of MF parallel to the direction of the incoming x-ray beam51. It does change sign upon reversal of MF. In the surface-sensitive total electron yield (TEY) mode, the sample current induced by the photoemitted electrons with an escape depth of 2–3 nm is probed52. In the bulk sensitive substrate fluorescence yield (FY) mode, the measurement signal originates from the x-rays transmitted through the magnetic layer stack generating fluorescence in the MgO substrates, which is probed by a photo diode53. The experimental geometry is shown in Fig. The antiferromagnetic order in Mn3 edge of Fe54, the AFM XMLD contrast at the L3 edge of Mn30. The SPELEEM microscope (Elmitec GmbH) of the MAXPEEM beamline provides, due to its perpendicular photon incidence on the sample surface, the highest possible AFM contrast for the in-plane orientation of the Néel vector of Mn2Au.XMLD-photoelectron emission microscopy (PEEM) was performed with a perpendicular incidence of the photon beam at the MAXPEEM beamline of MAX IV, Lund. The FM XMLD contrast was obtained at the L31 differs from an ordinary SEM in that it is additionally equipped with a spin detector to analyse the net spin of outgoing secondary electrons from ferromagnetic materials. This enables a spatial mapping of the spin polarization and by extension of the domain structure with a spatial resolution of less than 30 nm. As a ferromagnet possesses an inherent spin asymmetry in its density of states, the outgoing population of secondary electrons (which are ejected from a broad binding energy range) is spin-polarized. These secondary electrons undergo spin-dependent scattering at a W(100) single crystal via spin-polarized low-energy electron diffraction (SPLEED)55. Thus, up and down spin electrons are preferentially deflected towards separate electron counters and the difference of the count rates reflects the local magnetization direction.A SEMPAPeer Review File


The as-synthesized samples were analyzed using X-ray diffraction (XRD) and impedance spectroscopy. The emergence of orthorhombic phase fit into space group Pnmm was revealed by XRD, and the addition of Ca resulted in a considerable shift in grain size. Dielectric properties were determined using an impedance spectroscopy in a wide frequency range from 1MHz to 3 GHz. The dielectric properties i.e., dielectric constant (εr) and dielectric loss (1−xCax)Ti4O9 a prominent energy storage material. This study provides the possibility to improve its dielectric properties and reduce energy loss, making it an excellent energy storage material.The current research examines the impact of Ca When Ca2+ occupies the position of barium in the BT4 sample, the orthorhombic phase of Ba1−xCaxTi4O9 (BCT4) emerges. In addition, the doping of Ca2+ improves the dielectric and electrical properties of the ceramic compounds for electrical and dielectric resonator applications [4O9 ceramics have good dielectric properties i.e., high relative permittivity (εr = 36), good quality factor (Q = 3260 GHz), or low loss (Tanδ = 0.00048) and temperature coefficient of resonant frequency (τf = +24 ppm/°C). BT4 or BT-based solid solutions with further B-site or A-site doping components  are the most important dielectric ceramics, which improve the microwave dielectric properties [Owing to remarkable chemical as well as electrical properties, barium titanate (BT) has traditionally been regarded as developing dielectric material. Barium tetra titanate nanoparticles have recently received a lot of interest due to their numerous applications in modern communication technologies, such as software radio systems, global positioning systems (GPS), and environmental monitoring satellites. In addition, a high-quality resonators component has been used for high-speed communication systems, data storage devices, rechargeable batteries, and many more microwave dielectric applications. To improve the microwave dielectric properties, most laboratories and enterprises provide some micro-level oscillators and microwave frequency filters at low cost ,2. Ceramrequency . Moreoveoperties ,7. Meanwications . Becauseoperties ,11. In aoperties .1−xCax)Ti4O9  has been investigated.In the present research work, the phase, electrical, and dielectric properties of the sintered solid solution ceramics (Ba1−xCax)Ti4O9  calcined ceramics was obtained using conventional route. High-grade reactant raw powders were selected and weighed according to the stoichiometric ratio; these powders were purchased from Aldrich Chemicals  and sigma . These weighed powders were mixed in a distilled water medium for six (06) hours using horizontal ball milling. The wet mixture was dried by keeping it in oven at 100 °C for one day. The dried material was re-milled (in dry form) for two (2) hours before being calcined in an alumina crucible of high purity for 3 h in a furnace at 900 °C with 5 °C/min heating cooling rate. The calcined powder was manually crushed for one hour with a mortar and pestle to prevent agglomeration. The ground fine calcined powder was pressed into cylindrical dye with a diameter of 10 mm and thickness of 5 mm using of manual pellet press machine  at 100 MPa pressure. These pellets were indorsed with sintering at 1000 °C for 4 h in air with a heating cooling rate of 5 °C/min. The Archimedes principle can be used to measure the apparent bulk densities of the ceramic samples. At microwave frequency, the samples’ dielectric characteristics and minimal dielectric loss were determined using an impedance analyzer .The solid solution of (Ba1−xCax)Ti4O9 with various Ca2+ contents is shown in 4O9 (compared with reference card number 34–70) is responsible for all diffraction peaks, with lattice parameters of a = 6.294(5) Å, b = 14.532(11) Å, and c = 3.797(3) Å. Many peaks have been identified previously along with secondary phase  with reference card number (PDF No.80–916) [2+ concentrations on the structural properties of (Ba1−xCax)Ti4O9 ceramics has been recorded [2+ content in (Ba1−xCax)Ti4O9 rises. This could be attributed to micro strain, solid-state inhomogeneity, or the substitution of Ba2+(RBa = 1.44) for the comparatively enormous radius of Ca2+ (RCa = 1.57Å) for Ba2+ (RBa = 1.44Å) [The phase analysis profile of (Ba.80–916) . The inf= 1.44Å) .4O9), which increase with the increase of Ca2+ contents in (Ba1−xCax)Ti4O9 concentration, indicating that the particles gradually participate with the increase of Ca content.The crystalline nature of orthorhombic structure barium tetra titanate is attributed to the highly intense peaks and strong diffraction pattern as shown in x) of X-ray can be observed using the following formula:The density  while experimental densities can be determined using the Archimedes principle (density meter MD-35). Then we find the relative densities as shown in The mobility of the electric dipole generated by the applied electric field is usually the source of dielectric relaxation. The impact of applied electric field on the dielectric materials has been described using the Debye–Scherer relaxation model . The como’ is the permittivity of free space. 1−xCax) Ti4O9  sintered ceramics, at 1000 °C for 4 h. At low frequencies, the dielectric constant is very large, but it drops dramatically as frequency increases, eventually becoming constant at high frequencies. Ionic, electronic, interface, and orientation polarization are the four types of polarization that can be used to understand this behavior. Because each of these polarization mechanisms has its unique relaxation time, changes in applied frequency have an impact on charge carrier hopping. [εʹ) increases with increasing Ca2+ concentration until x = 0.9, where it starts to decline. Because the atomic polarizability of Ca2+ is higher than that of Lanthanum (La), the dielectric constant increases until x = 0.9. Though, at contents (x = 0.9) the sample porosity increases and, the grains size decreases, leading to an increase in resistivity, and polarization becomes incredibly difficult, potentially lowering the dielectric constant. The largest value of actual dielectric constant is attained for compositions with larger grain size [A capacitor’s storage capacity may be increased using dielectric materials. Therefore, the material’s capacitance is proportional towards its dielectric constant.hopping. ,18. At lain size . Accordip’ is parallel capacitance, ‘Rp’ parallel resistance while ‘tan δ’ is loss tangent or dielectric loss.When the parallel plate capacitor is connected to an external power supply source, the current leads the voltage by phase angle 90° which causes the power dissipation due to the leakage of current. As a result, the tangent loss may be determined using the following formula:1−xCax) Ti4O9  sintered at 1000 °C for 4 h. It is noted that both have the same tan loss trend relative to the Ca2+ content. These trends follow the Maxwell–Wagner interface polarization model, which aligns with Koop’s Phenomenological Theory (KPT). The dielectric materials are modeled as multilayer capacitors with grain edges and grains [The ideal capacitor has zero loss angle, and consumes zero power. Power dissipations are commonly referred to as dielectric loss in commercial capacitors and will be evaluated. This is depicted in d grains ,20. The dc’ is the conductivity of DC, ‘A’ is the pre-exponential factor and ‘s’ is the exponent. The phrase ‘ac conductivity’ encompasses the entire concept of Aωs. The following formula [Conductivity is defined as the movement of charge carrier under the action of applied field. The conductivity increases gradually at lower frequencies, but at higher frequencies the conductivity abruptly increased. At lower frequencies, the resistive nature of grain boundaries becomes more complicated, resulting in a low conductivity value being observed . The hig formula  can be uac) versus frequency (f) for (Ba1−xCax) Ti4O9  sintered ceramic pellets at 1000 °C for 4 h. The change in conductivity is minimal at first, but as the frequency increases, the conductivity increases dramatically. The hopping process and carrier mobility may be stimulated by increasing frequency; however, the free carrier may also consider the bound charge to conduct at high frequency. The cationic disorder caused by Ca2+ substitutions of smaller cations at the A-site may boost the conductivity by creating oxygen vacancies in the lattice skeleton at the 48f site [48f site .2+ concentration has a significant impact on microwave dielectric parameters such as dielectric constant (εr), quality factor (Q × f) and temperature coefficient of resonant frequency (τf). At a frequency of 3 GHz, the dielectric characteristics of sintered ceramics samples were investigated.Ca1−xCax) Ti4O9  sintered ceramic at 1000 °C for 4 h. At 1.5 GHz, there is a good quality factor and low loss dielectrics, making it excellent for microwave dielectric resonator applications. The temperature coefficient of resonance frequency (τf) is virtually zero for good tunable and silent circuits. However, we observed that due to the formation of the secondary phase, the values of temperature coefficient of resonance frequency (τf) increases with increasing the Ca2+ concentrations. As the sintering temperature rises, porosity decreases and grains become more tightly connected, increasing density. Similarly, sintering temperature has an impact on relative permittivity.Impedance spectroscopy is a useful tool for investigating the role of grains and grain boundaries, as well as the polarization mechanism. Some properties of solids depend on the capacitance and resistance values of individual microstructures, which are crucial in determining the dielectric response of materials. This technique enables us to estimate the resistance and capacitance provided by the bulk and grain boundaries and helps us find the relaxation time and frequency. The frequency dependence of impedance in complex form can be written as:Dielectric loss′’ is real impedance while ‘Z″’ is imaginary impedance.Complex impedance′ and the imaginary part of impedance Z″ is known as the Nyquist plot. The analysis shows that the magnitude of Z′ decreases with increasing frequency and temperature, indicating the ac conductivity ′ decreases significantly with the increase of Ca2+ substitution. At high frequency, the value of Z′ seems to be frequency independent, which indicates that the increase of Ca2+ concentration increases the temperature and leads to the increase of conductivity. The merging of the Z′ curves in the higher frequency region is probably the space charge released by the decrease of the barrier performance of the samples. It is also observed that the frequency at which the Z′ curves coincide increases with the increase of Ca2+ content. On the other hand, ′ and M″ are the real and imaginary parts of the complex modulus, respectively, as determined by the following relations [To analyze the electrical and relaxation properties of materials, complex impedance spectroscopy is an important technique. It provides important information about the stability of electrical behavior by studying the hopping of charge carriers and material homogeneous or heterogeneous properties. The electrical properties of bulk samples can be obtained by this technique because the study is more sensitive to the bulk properties of samples. The complex modulus M* is the inverse of complex dielectric constant ε*, i.e., elations :′’ real modulus while ‘M″’ is imaginary modulus.Complex electrical Modulus2+ substitution enhances the grain boundaries, which shift the plots towards the high value of M′, leading to an increase in capacitance of the samples.1−xCax)Ti4O9  ceramics has been investigated. The phase analysis shows that the impurity-free orthorhombic phase structure along with space group (Pnmm) is formed at (x = 0.0), the lattice parameters decrease with the substitution of Ca2+, and the unit cell volume also decreases. Impedance analysis revealed that the value of dielectric constant increases while increasing the Ca2+ contents due to their high atomic polarizability and decreases further due to increasing the sample porosities. Frequency-dependent ac conductivity was found to increase with increasing Ca2+ content due to the growth of grain boundaries and ionic polarizabilities. Complex modulus analysis investigated the various types of charge carrier mobility. The obtained results from this research are suitable for charge storage devices as well as for microwave wireless communication system applications.The solid-state solution of (Ba


The aim of this study was to compare the outcomes of right hemicolectomy with CME performed with laparoscopic and open surgery.ClinicalTrials.gov register were searched. Primary outcome was the overall number of harvested lymph nodes. Secondary outcomes were short and long-term course variables. A meta-analysis was performed to calculate risk ratios.PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Google Scholar and the P = 0.22). The only RCT shows a significant advantage in favour of laparoscopy . The analysis of CCTs showed an advantage in favour of the laparoscopic group, but the result was not statically significantly . The overall incidence of local recurrence was not different between the groups, while systemic recurrence at 5 years was lower in laparoscopic group. Laparoscopy showed better short-term outcomes including overall complications, lower estimated blood loss, lower wound infections and shorter hospital stay, despite a longer operative time. The rate of anastomotic and chyle leak was similar in the two groups.Twenty-one studies were identified with 5038 patients enrolled. The difference in number of harvested lymph nodes was not statistically significant (MD 0.68, − 0.41–1.76, Despite the several limitations of this study, we found that the median number of lymph node harvested in the laparoscopic group is not different compared to open surgery. Laparoscopy was associated with a lower incidence of systemic recurrence.The online version contains supplementary material available at 10.1007/s00384-021-03891-0. Colorectal cancer (CRC) is one of the most common health-threatening diseases around the globe. It is the third most frequent cancer worldwide  and, according to predictions, is expected to increase in incidence by a further 20% before 2030  OR “laparoscopy”[All Fields] OR “laparoscopic”[All Fields]) AND  AND open[All Fields] AND right[All Fields] AND CME[All Fields] (“laparoscopy”[MeSH Terms] OR “laparoscopy”[All Fields] OR “laparoscopic”[All Fields]) AND  AND open[All Fields] AND complete[All Fields] AND mesocolic[All Fields] AND excision[All Fields](“laparoscopy”[MeSH Terms] OR “laparoscopy”[All Fields] OR “laparoscopic”[All Fields]) AND CME[All Fields] AND open[All Fields] AND right[All Fields] AND (“colectomy”[MeSH Terms] OR “colectomy”[All Fields])(“laparoscopy”[MeSH Terms] OR “laparoscopy”[All Fields] OR “laparoscopic”[All Fields]) AND open[All Fields] AND central[All Fields] AND (“blood vessels”[MeSH Terms] OR (“blood”[All Fields] AND “vessels”[All Fields]) OR “blood vessels”[All Fields] OR “vascular”[All Fields]) AND (“ligation”[MeSH Terms] OR “ligation”[All Fields]) AND right[All Fields] AND (“colectomy”[MeSH Terms] OR “colectomy”[All Fields])The following search statement was used in Medline/PubMed:laparoscopic AND open AND right AND colectomylaparoscopic AND CME AND open AND right AND colectomylaparoscopic AND complete mesocolic excision AND open AND right AND colectomyIn the other databases , the search was performed by entering the association of the following keywords:ClinicalTrials.gov was searched to evaluate any ongoing registered clinical trials.A further search was performed through the reference lists of the selected articles and relevant grey literature on Google Scholar. Finally, Studies that compared participants enrolled for either laparoscopic or open right hemicolectomy with CME were eligible for inclusion. Randomized controlled trials (RCTs) and clinical control studies (CCTs) (prospective and retrospective cohort studies) were included. Case report studies were excluded.Two reviewers (RC and SZ) performed the search independently. A third author (AA) arbitrated any disagreements on inclusion or exclusion of studies. The reference lists of the included studies were searched manually. Only the data for patients who had undergone open or laparoscopic CME were included.Primary outcome was the overall number of harvested lymph nodes. Secondary outcomes were local and systemic recurrence at 3 and 5 years, operative time, post-operative mortality at 30 days, overall post-operative complications at 30 days, estimated blood loss, surgical intraoperative complications , anastomotic leak rate, chyle leak rate, post-operative hospital stay, post-operative ileus, wound infections and pulmonary infections.All studies fulfilling the selection criteria for this systematic review and meta-analysis were assessed for methodological quality and risk of bias by two authors (RC and GA). The individual scores of quality assessment items per study were assessed using the Cochrane risk tool for Randomised Control Trials , 11 and I2 and the Cochrane’s Q were reported as statistical measures of heterogeneity. For outcomes with more than ten studies, funnel plots are shown. Other statistical measures of bias are not reported given the high study heterogeneity. The data analysis was performed using the meta-analysis software Review Manager (RevMan) v 5.3.5 .All analyses were performed according to original treatment allocation . The categorical variables were described as absolute/relative frequencies and the continuous ones as median and interquartile range (IQR). Data were analysed for risk ratios (RR) in the case of dichotomous variables, and weighted mean differences (WMD) for continuous variables. The randomised Mantel-Haenszel method was used for the meta-analysis. All results were displayed in Forest plots. The In this meta-analysis, a subgroup analysis according to the types of study design was performed. We also identified the studies which had both the largest variance  and the extreme outlier weight in each clinical outcome group.ClinicalTrials.gov as NCT03826446) [The PRISMA flow diagram is presented in Fig. 3826446) .Fig. 1PrAltogether, the 21 studies included provided data on 5038 patients  , 16 and Among the examined studies, patients with stage IV disease were excluded, except for one . The othConcerning tumour localisation, all of the studies considered cancers of cecum, ascending colon and hepatic flexure, while only five studies , 31, 32 For what it concerns conversion from laparoscopic to open resection, most of the studies excluded the patients which required this procedure for any reason. From those other studies that considered in their data also converted surgeries, we excluded the converted procedures in our analysis.We assessed the risk of bias for each trial and summarised them using the criteria and the ‘Risk of bias’ Table (SDC 3). No data were reported on random sequence generation or allocation concealment in the RCT, while blinding of participants and personnel was not reported. A ‘low risk of bias’ was reported in the analysis of the attrition bias and an ‘unclear risk of bias’ for selective reporting. Risks of bias assessed with the MINORS scale quality assessment for non-RCTs is reported in SDC 4. The mean score was 16 (moderate risk).P = 0.22, I2 = 90%).The overall number of harvested lymph nodes was reported in 3876 patients (19 studies) , 24–35. P = 0.04). However, the analysis of CCTs showed an advantage in favour of the laparoscopic group, but not statically significant   shows a significant advantage in favour of laparoscopy . The incidence of overall recurrence was significantly lower in the laparoscopic group  (SDC 5).Overall recurrence at 3 years was reported in 3 studies , 16, 24 n = 1860). The incidence of overall recurrence was significantly lower in the laparoscopic group  (SDC 6).Overall recurrence at 5 years was reported in 3 studies , 31, 33 n = 414). The overall incidence of local recurrence was significantly lower in the laparoscopic group  (SDC 7).Local recurrence at 3 years was reported in 3 studies , 16, 24 n = 1944). The overall incidence of local recurrence was not different between the groups  (SDC 8).Local recurrence at 5 years was reported in 4 CCTs , 31, 33 n = 354). The overall incidence of systemic recurrence was not different between the groups  (SDC 9).Systemic recurrence at 3 years was reported in 2 CCTs , 24 (n =n = 1860). The overall incidence of systemic recurrence was significantly lower in laparoscopic group  (SDC 10).Systemic recurrence at 5 years was reported in 3 CCTs , 31, 33 P < 0.00001; I2 = 94%) . No statistically significant difference was observed between the two groups  (SDC 11).Nine studies , 31–33 rI2 = 95%)  Fig. .Fig. 4FoI2 = 0%) (SDC 12).Four studies , 32, 33 P = 0.02, I2 = 0%) (SDC 13).Twelve studies , 30–33 rP = 0.47, I2 = 0%)  was reported in 15 studies , 30–33 (n = 1293). These did not differ between groups  . This was significantly lower in the laparoscopic group compared to the open group  (SDC 14).Six studies , 30, 34,n = 2906). No statistically significant difference was observed between the two groups  (SDC 15).Ten studies , 31, 33 n = 1322). These were significantly fewer in the laparoscopic group compared to the open group  (SDC 16).Eigth studies , 31, 33 n = 774). No statistically significant difference was observed between the two groups  (SDC 17).Four studies , 24, 33 The CME technique as part of a right hemicolectomy is technically difficult because of the large variability in the right colon vasculature, which may be the cause of challenging intraoperative bleeding complications. Moreover, CME should be performed by surgeons with a significant experience in colorectal surgery. It is important to recall that the localisation of the disease influences the extent of lymphadenectomy in the peripancreatic area: for experts of the CME technique, cancers located in the hepatic flexure and in proximal transverse colon require extension to the Henle trunk stations.Several authors have published their data and results in the execution of CME in a laparoscopic setting, which clearly requires further experience in advanced laparoscopic surgery. The choice between laparoscopy or open surgery for CME remains a point of discussion and interest. Moreover, some argue that CME may be an appropriate indication for a robotic approach , 50, andWe compared laparoscopic and open CME in terms of the number of lymph nodes harvested. Moreover, we evaluated the differences in long-term prognosis considering the 3-year and 5-year post-operative overall survival and disease-free survival. Local control of the disease is improved by an increased number of harvested lymph nodes . The samLaparoscopic CME may allow more lymph nodes to be harvested than in open surgery. Nevertheless, laparoscopy appeared superior to open surgery in terms of overall recurrence at 3 and 5 years, the only measurable parameter related to oncologic adequacy. However, there needs to be caution in interpretation of this result due to the possible influence of selection bias.Improved staging of the disease does allow patients to be considered for the most appropriate therapeutic approach, in particular the receipt of adjuvant chemotherapy. Han et al.  also shoBesides extended lymphadenectomy, CME requires the mesocolic fascia to be excised intact, in order to guarantee advantages in term of oncological radicality and survival , 51–53. It is important to remember that laparoscopic approach may fail and require conversion to open surgery because of various reasons: the main factor that implicates conversion is a vascular injury that leads to uncontrollable bleeding or that cannot be detected in its source; other conditions that could require the change of procedure could be the excess of adhesions or an organ injury hard to repair laparoscopically. In case of conversion to the open approach, there are consequences for the patient that must be considered and discussed before choosing this method: in particular, the outcome of the patient worsens in term of longer and complicated post-operative stay, the possible need for post-operative ICU and longer operative time. These complications are a direct consequence of the conversion and are not a consequence of the open technique, that is why it is very important to select the patients that will undergo laparoscopic surgery , 55.The presented data show laparoscopy to be at least non inferior to open surgery when performing CME for cancer of the right colon, with other benefits of a minimally invasive approach also confirmed. Moreover, the laparoscopy group resulted in a lower 5-year systemic recurrence rate, even if this outcome was reported by only a few studies: the results might be considered promising but will need further confirmation by the enlargement of the cohort of studies. Laparoscopy offered better short-term outcomes including overall complications, lower estimated blood loss and lower wound infection rates, altogether translating into a shorter hospital stay. This appears at the expense of a longer operative time, likely due to the higher technical difficulty associated with the surgery, in particular when a laparoscopic extended right hemicolectomy is performed for tumours located at the hepatic flexure or proximal transverse colon. These endpoints are similar to other meta-analyses , 38 regaThe current study has several limitations. Although this systematic review included the highest number of studies reported in literature, the major limitation is represented by the geographical distribution of the studies. In fact, all but one studies which was performed in Germany  were pubAnother developing field in the group of minimally invasive techniques is robotic surgery: some studies , 57 analIn conclusion, the present systematic review and meta-analysis fails to show that a laparoscopic approach appears non-inferior to open surgery in terms of lymph nodes harvested but showed a benefit in terms of incidence of systemic recurrence, when performing right hemicolectomy with CME for colon cancer, while maintaining the usual benefits of a minimally invasive surgical approach.Nevertheless, further prospective and randomised studies are awaited to increase the quantity of data and quality of the evidence.ESM 1(DOCX 15 kb)ESM 2(DOCX 53 kb)ESM 3(DOCX 24 kb)ESM 4(DOCX 27 kb)ESM 5(DOCX 19 kb)ESM 6(DOCX 27 kb)ESM 7(DOCX 20 kb)ESM 8(DOCX 19 kb)ESM 9(DOCX 20 kb)ESM 10(DOCX 29 kb)ESM 11(DOCX 20 kb)ESM 12(DOCX 31 kb)ESM 13(DOCX 22 kb)ESM 14(DOCX 31 kb)ESM 15(DOCX 30 kb)ESM 16(DOCX 20 kb)