Electrical switching of magnetic order in an orbital Chern insulator.

Magnetism typically arises from the joint effect of Fermi statistics and repulsive Coulomb interactions, which favours ground states with non-zero electron spin. As a result, controlling spin magnetism with electric fields-a longstanding technological goal in spintronics and multiferroics1,2-can be achieved only indirectly. Here we experimentally demonstrate direct electric-field control of magnetic states in an orbital Chern insulator3-6, a magnetic system in which non-trivial band topology favours long-range order of orbital angular momentum but the spins are thought to remain disordered7-14. We use van der Waals heterostructures consisting of a graphene monolayer rotationally faulted with respect to a Bernal-stacked bilayer to realize narrow and topologically non-trivial valley-projected moiré minibands15-17. At fillings of one and three electrons per moiré unit cell within these bands, we observe quantized anomalous Hall effects18 with transverse resistance approximately equal to h/2e2 (where h is Planck's constant and e is the charge on the electron), which is indicative of spontaneous polarization of the system into a single-valley-projected band with a Chern number equal to two. At a filling of three electrons per moiré unit cell, we find that the sign of the quantum anomalous Hall effect can be reversed via field-effect control of the chemical potential; moreover, this transition is hysteretic, which we use to demonstrate non-volatile electric-field-induced reversal of the magnetic state. A theoretical analysis19 indicates that the effect arises from the topological edge states, which drive a change in sign of the magnetization and thus a reversal in the favoured magnetic state. Voltage control of magnetic states can be used to electrically pattern non-volatile magnetic-domain structures hosting chiral edge states, with applications ranging from reconfigurable microwave circuit elements to ultralow-power magnetic memories.

Phonon Hall Viscosity of Ionic Crystals.

When time-reversal symmetry is broken, the low-energy description of acoustic lattice dynamics allows for a dissipationless component of the viscosity tensor, the phonon Hall viscosity, which captures how phonon chirality grows with the wave vector. In this work, we show that, in ionic crystals, a phonon Hall viscosity contribution is produced by the Lorentz forces on moving ions. We calculate typical values of the Lorentz force contribution to the Hall viscosity using a simple square lattice toy model, and we compare it with literature estimates of the strengths of other Hall-viscosity mechanisms.

Defining tetrahydrobiopterin responsiveness in phenylketonuria: Survey results from 38 countries.

BACKGROUND: A subset of patients with phenylketonuria benefit from treatment with tetrahydrobiopterin (BH4), although there is no consensus on the definition of BH4 responsiveness. The aim of this study therefore was to gain insight into the definitions of long-term BH4 responsiveness being used around the world. METHODS: We performed a web-based survey targeting healthcare professionals involved in the treatment of PKU patients. Data were analysed according to geographical region (Europe, USA/Canada, other). RESULTS: We analysed 166 responses. Long-term BH4 responsiveness was commonly defined using natural protein tolerance (95.6%), improvement of metabolic control (73.5%) and increase in quality of life (48.2%). When a specific value for a reduction in phenylalanine concentrations was reported (n = 89), 30% and 20% were most frequently used as cut-off values (76% and 19% of respondents, respectively). When a specific relative increase in natural protein tolerance was used to define long-term BH4 responsiveness (n = 71), respondents most commonly reported cut-off values of 30% and 100% (28% of respondents in both cases). Respondents from USA/Canada (n = 50) generally used less strict cut-off values compared to Europe (n = 96). Furthermore, respondents working within the same center answered differently. CONCLUSION: The results of this study suggest a very heterogeneous situation on the topic of defining long-term BH4 responsiveness, not only at a worldwide level but also within centers. Developing a strong evidence- and consensus-based definition would improve the quality of BH4 treatment.

Development and internal validation of clinical prediction models for outcomes of complicated intra-abdominal infection.

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse. METHODS: A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further. RESULTS: Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively. CONCLUSION: Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.

Weak-Field Hall Resistivity and Spin-Valley Flavor Symmetry Breaking in Magic-Angle Twisted Bilayer Graphene.

Near a magic twist angle, the lowest energy conduction and valence bands of bilayer graphene moiré superlattices become extremely narrow. The band dispersion that remains is sensitive to the moiré's strain pattern, nonlocal tunneling between layers, and filling-factor-dependent Hartree and exchange band renormalizations. In this Letter, we analyze the influence of these band-structure details on the pattern of flavor symmetry breaking observed in this narrow band system and on the associated pattern of Fermi surface reconstructions revealed by weak-field Hall and Shubnikov-de Haas magnetotransport measurements.

Exact Diagonalization for Magic-Angle Twisted Bilayer Graphene.

We report on finite-size exact-diagonalization calculations in a Hilbert space defined by the continuum-model flat moiré bands of magic angle twisted bilayer graphene. For moiré band filling 3>|ν|>2, where superconductivity is strongest, we obtain evidence that the ground state is a spin ferromagnet. Near |ν|=3, we find Chern insulator ground states that have spontaneous spin, valley, and sublattice polarization, and demonstrate that the anisotropy energy in this order-parameter space is strongly band-filling-factor dependent. We emphasize that inclusion of the remote band self-energy is necessary for a reliable description of magic angle twisted bilayer graphene flat band correlations.

WKB Estimate of Bilayer Graphene's Magic Twist Angles.

Graphene bilayers exhibit zero-energy flatbands at a discrete series of magic twist angles. In the absence of intrasublattice interlayer hopping, zero-energy states satisfy a Dirac equation with a non-Abelian SU(2) gauge potential that cannot be diagonalized globally. We develop a semiclassical WKB approximation scheme for this Dirac equation by introducing a dimensionless Planck's constant proportional to the twist angle, solving the linearized Dirac equation around AB and BA turning points, and connecting Airy function solutions via bulk WKB wave functions. We find zero-energy solutions at a discrete set of values of the dimensionless Planck's constant, which we obtain analytically. Our analytic flatband twist angles correspond closely to those determined numerically in previous work.

Complications and functional outcomes after ileo-anal pouch excision-a systematic review of 14 retrospective observational studies.

PURPOSE: The ileo-anal pouch (IAP) has been the gold standard procedure for maintenance of bowel continuity after panproctocolectomy for ulcerative colitis, familial adenomatous polyposis or hereditary non-polyposis colorectal cancer. However, the IAP has an estimated failure rate of 13% at 10 years post-procedure (Tulchinsky et al., Ann Surg 238(2):229-34, 2003), which can result in pouch excision (P.E.). This systematic review aims to synthesise all the available studies reporting post-operative outcomes of P.E. and its impact on patient quality of life (QoL), when available, which have not previously been summarised. METHODS: PubMed, Embase, Medline and the Cochrane library databases were searched with terms 'Pouch AND excision' OR 'Pouch AND removal' OR 'Pouch AND remove' OR 'IAP AND excision'. All studies reporting post-operative morbidity, mortality or functional outcomes in patients who had P.E. were included. Studies with < 5 patients, non-English studies and conference abstracts were excluded. RESULTS: 14 studies comprising 1601 patients were included. Overall complications varied from 18 to 63% with the most common being persistent perineal sinus (9-40%) or surgical site infection (wound-2 to 30%; intra-abdominal collection-3 to 24%). The mortality rate was between 0.58 and 1.4%. QoL is generally lower in P.E. patients compared to the normal population across various QoL measures and P.E. patients often had urinary and sexual dysfunction post-operatively. CONCLUSIONS: There is a substantial incidence of complications after P.E.; however, there is no evidence describing QoL pre- and post-P.E. Further longitudinal research comparing QoL in patients undergoing P.E. and other treatment options such as indefinite diversion is required to definitively assess QoL post-procedure.

Grassland biodiversity bounces back from long-term nitrogen addition.

The negative effect of increasing atmospheric nitrogen (N) pollution on grassland biodiversity is now incontrovertible. However, the recent introduction of cleaner technologies in the UK has led to reductions in the emissions of nitrogen oxides, with concomitant decreases in N deposition. The degree to which grassland biodiversity can be expected to 'bounce back' in response to these improvements in air quality is uncertain, with a suggestion that long-term chronic N addition may lead to an alternative low biodiversity state. Here we present evidence from the 160-year-old Park Grass Experiment at Rothamsted Research, UK, that shows a positive response of biodiversity to reducing N addition from either atmospheric pollution or fertilizers. The proportion of legumes, species richness and diversity increased across the experiment between 1991 and 2012 as both wet and dry N deposition declined. Plots that stopped receiving inorganic N fertilizer in 1989 recovered much of the diversity that had been lost, especially if limed. There was no evidence that chronic N addition has resulted in an alternative low biodiversity state on the Park Grass plots, except where there has been extreme acidification, although it is likely that the recovery of plant communities has been facilitated by the twice-yearly mowing and removal of biomass. This may also explain why a comparable response of plant communities to reduced N inputs has yet to be observed in the wider landscape.

The effect of organic carbon content on soil compression characteristics.

We investigated the effect of soil organic carbon (SOC) on the consolidation behaviour of soil from two long term field experiments at Rothamsted; the Broadbalk Wheat Experiment and Hoosfield Spring Barley. These experiments are located on soil with similar particle size distributions, and include treatments with SOC contents ranging from approximately 1-3.5 g/100 g. Soils taken from plots with contrasting SOC contents were compressed and deformed in a triaxial cell and the normal consolidation and critical state lines were determined. We found that the compression index was independent of SOC, but the void ratio at any given effective stress was highly correlated with organic carbon content. By comparison with uniaxial compression data, the apparent influence of SOC on the compression index is likely to be due to its effect on soil hydraulic properties rather than any intrinsic effects of strength. The plastic limit test appears to be a useful and simple test to allow direct comparison of soil physical behaviour and expected soil density.

Nature of the Correlated Insulator States in Twisted Bilayer Graphene.

We use self-consistent Hartree-Fock calculations performed in the full π-band Hilbert space to assess the nature of the recently discovered correlated insulator states in magic-angle twisted bilayer graphene (TBG). We find that gaps between the flat conduction and valence bands open at neutrality over a wide range of twist angles, sometimes without breaking the system's valley projected C_{2}T symmetry. Broken spin-valley flavor symmetries then enable gapped states to form not only at neutrality, but also at total moiré band filling n=±p/4 with integer p=1, 2, 3, when the twist angle is close to the magic value at which the flat bands are most narrow. Because the magic-angle flat band quasiparticles are isolated from remote band quasiparticles only for effective dielectric constants larger than ∼20, the gapped states do not necessarily break C_{2}T symmetry and as a consequence the insulating states at n=±1/4 and n=±3/4 need not exhibit a quantized anomalous Hall effect.

Voltage-Controlled Magnetic Reversal in Orbital Chern Insulators.

Chern insulator ferromagnets are characterized by a quantized anomalous Hall effect and have so far been identified experimentally in magnetically doped topological insulator thin films and in bilayer graphene moiré superlattices. We classify Chern insulator ferromagnets as either spin or orbital, depending on whether the orbital magnetization results from spontaneous spin polarization combined with spin-orbit interactions, as in the magnetically doped topological insulator case, or directly from spontaneous orbital currents, as in the moiré superlattice case. We argue that, in a given magnetic state, characterized, for example, by the sign of the anomalous Hall effect, the magnetization of an orbital Chern insulator will often have opposite signs for weak n and weak p electrostatic or chemical doping. This property enables pure electrical switching of a magnetic state in the presence of a fixed magnetic field.

Infrared thermography and ulcer prevention in the high-risk diabetic foot: data from a single-blind multicentre controlled clinical trial.

AIM: To assess the usefulness of monthly thermography and standard foot care to reduce diabetic foot ulcer recurrence. METHODS: People with diabetes (n = 110), neuropathy and history of ≥ 1 foot ulcer participated in a single-blind multicentre clinical trial. Feet were imaged with a novel thermal imaging device (Diabetic Foot Ulcer Prevention System). Participants were randomized to intervention (active thermography + standard foot care) or control (blinded thermography + standard foot care) and were followed up monthly until ulcer recurrence or for 12 months. Foot thermograms of participants from the intervention group were assessed for hot spots (areas with temperature ≥ 2.2°C higher than the corresponding contralateral site) and acted upon as per local standards. RESULTS: After 12 months, 62% of participants were ulcer-free in the intervention group and 56% in the control group. The odds ratios of ulcer recurrence (intervention vs control) were 0.82 (95% CI 0.38, 1.8; P = 0.62) and 0.55 (95% CI 0.21, 1.4; P = 0.22) in univariate and multivariate logistic regression analyses, respectively. The hazard ratios for the time to ulcer recurrence (intervention vs control) were 0.84 (95% CI 0.45, 1.6; P = 0.58) and 0.67 (95% CI 0.34, 1.3; P = 0.24) in univariate and multivariate Cox regression analyses, respectively. CONCLUSIONS: Monthly intervention with thermal imaging did not result in a significant reduction in ulcer recurrence rate or increased ulcer-free survival in this cohort at high risk of foot ulcers. This trial has, however, informed the design of a refined study with longer follow-up and group stratification, further aiming to assess the efficacy of thermography to reduce ulcer recurrence.

A nonmyeloablative chimeric mouse model accurately defines microglia and macrophage contribution in glioma.

AIMS: Resident and peripherally derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion and attenuating host immune responses. Differentiating these cells' origins is challenging and current preclinical models such as irradiation-based adoptive transfer, parabiosis and transgenic mice have limitations. We aimed to develop a novel nonmyeloablative transplantation (NMT) mouse model that permits high levels of peripheral chimerism without blood-brain barrier (BBB) damage or brain infiltration prior to tumour implantation. METHODS: NMT dosing was determined in C57BL/6J or Pep3/CD45.1 mice conditioned with concentrations of busulfan ranging from 25 mg/kg to 125 mg/kg. Donor haematopoietic cells labelled with eGFP or CD45.2 were injected via tail vein. Donor chimerism was measured in peripheral blood, bone marrow and spleen using flow cytometry. BBB integrity was assessed with anti-IgG and anti-fibrinogen antibodies. Immunocompetent chimerised animals were orthotopically implanted with murine glioma GL-261 cells. Central and peripheral cell contributions were assessed using immunohistochemistry and flow cytometry. GAMM subpopulation analysis of peripheral cells was performed using Ly6C/MHCII/MerTK/CD64. RESULTS: NMT achieves >80% haematopoietic chimerism by 12 weeks without BBB damage and normal life span. Bone marrow derived cells (BMDC) and peripheral macrophages accounted for approximately 45% of the GAMM population in GL-261 implanted tumours. Existing markers such as CD45 high/low proved inaccurate to determine central and peripheral populations while Ly6C/MHCII/MerTK/CD64 reliably differentiated GAMM subpopulations in chimerised and unchimerised mice. CONCLUSION: NMT is a powerful method for dissecting tumour microglia and macrophage subpopulations and can guide further investigation of BMDC subsets in glioma and neuro-inflammatory diseases.

Topological Insulators in Twisted Transition Metal Dichalcogenide Homobilayers.

We show that moiré bands of twisted homobilayers can be topologically nontrivial, and illustrate the tendency by studying valence band states in ±K valleys of twisted bilayer transition metal dichalcogenides, in particular, bilayer MoTe_{2}. Because of the large spin-orbit splitting at the monolayer valence band maxima, the low energy valence states of the twisted bilayer MoTe_{2} at the +K (-K) valley can be described using a two-band model with a layer-pseudospin magnetic field Δ(r) that has the moiré period. We show that Δ(r) has a topologically nontrivial skyrmion lattice texture in real space, and that the topmost moiré valence bands provide a realization of the Kane-Mele quantum spin-Hall model, i.e., the two-dimensional time-reversal-invariant topological insulator. Because the bands narrow at small twist angles, a rich set of broken symmetry insulating states can occur at integer numbers of electrons per moiré cell.

Magneto-Coulomb Drag and Hall Drag in Double-Layer Dirac Systems.

We develop a theory of Coulomb drag due to momentum transfer between graphene layers in a strong magnetic field. The theory is intended to apply in systems with disorder that is weak compared to Landau level separation, so that Landau level mixing is weak but strong compared to correlation energies within a single Landau level, so that fractional quantum Hall physics is not relevant. We find that, in contrast to the zero-field limit, the longitudinal magneto-Coulomb drag is finite and, in fact, attains a maximum at the simultaneous charge neutrality point (CNP) of both layers. Our theory also predicts a sizable Hall drag resistivity at densities away from the CNP.

Age at death and the effect of lead-time bias in patients with colorectal cancer: a 10-year follow-up.

AIM: Studies addressing the benefit of early intervention are prone to lead-time bias, which results in an artificial improvement in cancer-specific mortality. We have previously compared the age at death for patients with colorectal cancer presenting on an emergency or elective basis. In this study, we aimed to repeat the analysis with a minimum follow-up of 10 years. METHOD: A nonscreen-detected cohort of patients presenting with colorectal cancer to three Lanarkshire Hospitals between 2000 and 2006 were entered into a prospective database, with analysis performed on 28 November 2016. The following data were collected: age at death, presentation type (emergency/elective), operative intent (palliative/curative) and Dukes stage. Results are presented as [mean (95% confidence intervals)]. Statistical analysis was undertaken using Student's t-test and multivariate analysis performed using Cox proportional hazard models. RESULTS: One thousand six hundred and thirty-six patients were identified. Elective patients presented younger than emergency patients [67.9 (67.3-68.5) vs 70.9 (69.6-72.2) years; P < 0.0001]. Overall mortality was 71.1% at time of analysis; no difference was seen in the mean age at death between emergency and elective presentation [73.5 (72.4-74.8) vs 73.6 (72.3-74.9) years; P = 0.841]. CONCLUSION: Current early detection strategies to diagnose colorectal cancer may improve cancer-specific survival by increasing lead-time bias. However, in our cohort of symptomatic patients, treatment on an elective or emergency basis does not influence overall survival. These data suggest that in selected patients, particularly where there is comorbidity, it may be reasonable to adopt a more expectant approach to investigate and treat colorectal symptoms.

Interactive effects of climate change and biodiversity loss on ecosystem functioning.

Climate change and biodiversity loss are expected to simultaneously affect ecosystems, however research on how each driver mediates the effect of the other has been limited in scope. The multiple stressor framework emphasizes non-additive effects, but biodiversity may also buffer the effects of climate change, and climate change may alter which mechanisms underlie biodiversity-function relationships. Here, we performed an experiment using tank bromeliad ecosystems to test the various ways that rainfall changes and litter diversity may jointly determine ecological processes. Litter diversity and rainfall changes interactively affected multiple functions, but how depends on the process measured. High litter diversity buffered the effects of altered rainfall on detritivore communities, evidence of insurance against impacts of climate change. Altered rainfall affected the mechanisms by which litter diversity influenced decomposition, reducing the importance of complementary attributes of species (complementarity effects), and resulting in an increasing dependence on the maintenance of specific species (dominance effects). Finally, altered rainfall conditions prevented litter diversity from fueling methanogenesis, because such changes in rainfall reduced microbial activity by 58%. Together, these results demonstrate that the effects of climate change and biodiversity loss on ecosystems cannot be understood in isolation and interactions between these stressors can be multifaceted.

Electrical Reservoirs for Bilayer Excitons.

The ground state of two-dimensional (2D) electron systems with equal low densities of electrons and holes in nearby layers is an exciton fluid. We show that a reservoir for excitons can be established by contacting the two layers separately and maintaining the chemical potential difference at a value less than the spatially indirect band gap, thereby avoiding the presence of free carriers in either layer. Equilibration between the exciton fluid and the contacts proceeds via a process involving virtual intermediate states in which an unpaired electron or hole virtually occupies a free carrier state in one of the 2D layers. We derive an approximate relationship between the exciton-contact equilibration rate and the electrical conductances between the contacts and individual 2D layers when the contact chemical potentials align with the free-carrier bands, and explain how electrical measurements can be used to measure thermodynamic properties of the exciton fluids.

Time-Reversal Symmetry-Breaking Nematic Insulators near Quantum Spin Hall Phase Transitions.

We study the phase diagram of a model quantum spin Hall system as a function of band inversion and band-coupling strength, demonstrating that when band hybridization is weak, an interaction-induced nematic insulator state emerges over a wide range of band inversion. This property is a consequence of the long-range Coulomb interaction, which favors interband phase coherence that is weakly dependent on momentum and therefore frustrated by the single-particle Hamiltonian at the band inversion point. For weak band hybridization, interactions convert the continuous gap closing topological phase transition at inversion into a pair of continuous phase transitions bounding a state with broken time-reversal and rotational symmetries. At intermediate band hybridization, the topological phase transition proceeds instead via a quantum anomalous Hall insulator state, whereas at strong hybridization interactions play no role. We comment on the implications of our findings for InAs/GaSb and HgTe/CdTe quantum spin Hall systems.