The complex interplay of spin, charge, orbital and lattice degrees of freedom provides a plethora of exotic phases and physical phenomena. In recent years, complex spin topologies have emerged as a ...consequence of the electronic band structure and the interplay between spin and spin-orbit coupling in materials. Here we produce complex topologies of electrical polarization--namely, nanometre-scale vortex-antivortex (that is, clockwise-anticlockwise) arrays that are reminiscent of rotational spin topologies--by making use of the competition between charge, orbital and lattice degrees of freedom in superlattices of alternating lead titanate and strontium titanate layers. Atomic-scale mapping of the polar atomic displacements by scanning transmission electron microscopy reveals the presence of long-range ordered vortex-antivortex arrays that exhibit nearly continuous polarization rotation. Phase-field modelling confirms that the vortex array is the low-energy state for a range of superlattice periods. Within this range, the large gradient energy from the vortex structure is counterbalanced by the corresponding large reduction in overall electrostatic energy (which would otherwise arise from polar discontinuities at the lead titanate/strontium titanate interfaces) and the elastic energy associated with epitaxial constraints and domain formation. These observations have implications for the creation of new states of matter (such as dipolar skyrmions, hedgehog states) and associated phenomena in ferroic materials, such as electrically controllable chirality.
Complex topological configurations are fertile ground for exploring emergent phenomena and exotic phases in condensed-matter physics. For example, the recent discovery of polarization vortices and ...their associated complex-phase coexistence and response under applied electric fields in superlattices of (PbTiO
)
/(SrTiO
)
suggests the presence of a complex, multi-dimensional system capable of interesting physical responses, such as chirality, negative capacitance and large piezo-electric responses
. Here, by varying epitaxial constraints, we discover room-temperature polar-skyrmion bubbles in a lead titanate layer confined by strontium titanate layers, which are imaged by atomic-resolution scanning transmission electron microscopy. Phase-field modelling and second-principles calculations reveal that the polar-skyrmion bubbles have a skyrmion number of +1, and resonant soft-X-ray diffraction experiments show circular dichroism, confirming chirality. Such nanometre-scale polar-skyrmion bubbles are the electric analogues of magnetic skyrmions, and could contribute to the advancement of ferroelectrics towards functionalities incorporating emergent chirality and electrically controllable negative capacitance.
Summary
Background While the chronic inflammation related to autoimmune diseases is known to be associated with an increased cardiovascular risk, much less is known about cerebrovascular risks.
...Objectives The present population‐based, age‐ and sex‐matched follow‐up study was undertaken to investigate the risks of acute myocardial infarction (AMI) and ischaemic stroke in patients with dermatomyositis (DMS).
Methods In total 907 patients with DMS were enrolled and compared with a non‐DMS control group consisting of 4535 age‐ and sex‐matched, randomly sampled subjects without DMS. The AMI‐free and ischaemic stroke‐free survival curves were generated using the Kaplan–Meier method. Cox proportional hazard regression was used to estimate the DMS‐associated risks of AMI and ischaemic stroke.
Results During the 2‐year follow‐up period, 14 patients with DMS (1·5%) and 18 patients in the non‐DMS control group (0·4%) suffered AMIs. The crude hazard ratio (HR) for suffering an AMI in patients with DMS compared with subjects in the non‐DMS group was 3·96 95% confidence interval (CI) 1·97–7·96, P = 0·0001, while the adjusted HR was 3·37 (95% CI 1·67–6·80, P = 0·0007), after taking into account demographic characteristics and cardiovascular comorbidities. During the same follow‐up period, 46 patients (5·1%) and 133 subjects in the control group (2·9%) developed ischaemic strokes. The crude HR for developing an ischaemic stroke in patients with DMS compared with subjects in the non‐DMS group was 1·78 (95% CI 1·27–2·49, P = 0·0007), and the adjusted HR was 1·67 (95% CI, 1·19–2·34, P = 0·0028).
Conclusions These findings suggest that DMS is associated with an increased risk of cardiovascular and cerebrovascular events.
What’s already known about this topic?
•
Connective‐tissue disorders, such as rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus and primary vasculitis have been linked to an increased risk of cardiovascular disease.
•
Data on any association between dermatomyositis and cardiovascular or cerebrovascular disease is sparse.
What does this study add?
•
This population‐based, age‐ and sex‐matched longitudinal follow‐up study shows that dermatomyositis is associated with increased risks of acute myocardial infarction and ischaemic stroke.
Aim
Recent studies have shown that sarcopenia is associated with negative postoperative outcomes. However, none of these studies analysed muscle strength or physical performance, which are also ...important components of sarcopenia. The present study aimed to investigate whether sarcopenia itself, as defined by low muscle mass, strength and physical performance, would predict complications after surgery for colorectal cancer.
Method
We conducted a prospective study of patients who underwent surgery for colorectal cancer at our department between August 2014 and February 2015. Sarcopenia was diagnosed by a combination of third lumbar vertebra muscle index (L3 MI), handgrip strength and 6‐m usual gait speed. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. Only complications classified as Grade II or above according to the Clavien–Dindo classification were analysed in this study.
Results
A total of 142 patients were included in the study, and 17 patients were diagnosed as having sarcopenia. Postoperative complications of Grade II or above occurred in 40 patients, including 10 with sarcopenia and 30 without sarcopenia. Multivariate analysis showed that sarcopenia and previous abdominal surgery were independent risk factors for postoperative complications. Patients with sarcopenia also had an obvious tendency to a higher incidence of infectious complications. By comparing two logistic regression models, sarcopenia showed a better predictive power for postoperative complications than did low muscle mass.
Conclusion
Sarcopenia and previous abdominal surgery are independent risk factors for complications after surgery for colorectal cancer. Including a functional aspect to the definition of sarcopenia may result in a better prediction of postoperative complications.
Summary
The aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of balloon kyphoplasty (BK), percutaneous vertebroplasty (PVP), and ...non-surgical treatment (NST) for patients with osteoporotic vertebral compression fractures (OVCFs). The results demonstrate that for pain and functional status, PVP was significantly better than NST, while the three treatments did not significantly differ in other outcomes.
Introduction
BK, PVP, and NST are widely used to treat OVCFs, but preferable treatment is unknown. The aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of BK, PVP, and NST for patients with OVCFs.
Methods
PubMed, EMBASE, and the Cochrane Library were screened. Based on the preplanned eligibility criteria, we screened and included randomized controlled trials that compared BK, PVP, and NST in treating patients with OVCFs. The risk of bias for individual studies was appraised. The data were pooled using a Bayesian network meta-analysis and a traditional direct comparison meta-analysis.
Results
Of the 1057 relevant studies, 15 were eligible and included. Compared with NST, PVP significantly reduced pain, Oswestry Disability Index (ODI), and Roland–Morris Disability Questionnaire (RMDQ). The comparative efficacy of BK and PVP was similar for pain (mean difference (MD) 0.51, 95% credible interval (CrI) − 0.35 to 1.4), ODI (MD 0.11, 95% CrI − 13 to 13), and RMDQ (MD 1.2, 95% CrI − 2.7 to 5.4). The European Quality of Life–5 Dimensions (EQ–5D) and Physical Component Summary subscales of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36 PCS) did not differ significantly. There were also no substantial differences in the risks of subsequent vertebral fractures, adjacent vertebral fractures, and re-fractures at the treated level across all comparators. The results of pairwise meta-analyses were almost consistent with those of network meta-analyses. The treatment ranking indicated that PVP had the highest probability of being the most effective for pain, ODI, RMDQ, and EQ-5D. BK had the highest probability of improving SF-36 PCS and of reducing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST was ranked first in preventing adjacent vertebral fractures.
Conclusion
PVP was the most effective method for improving pain, functional status, and quality of life (based on EQ-5D). BK emerged as the best intervention for decreasing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST could be ranked first in reducing adjacent vertebral fractures. The future directions of OVCFs treatment will depend on the outcomes of additional and larger randomized trials in comparing BK with PVP.
Summary
Background
GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma HCC and Of its treatment with sorafeNib) is a global, prospective, non‐interventional study ...undertaken to evaluate the safety of sorafenib in patients with unresectable HCC in real‐life practice, including Child‐Pugh B patients who were excluded from clinical trials.
Methods
Patients with unresectable HCC, for whom the decision to treat with sorafenib, based on the approved label and prescribing guidelines, had been taken by their physician, were eligible for inclusion. Demographic data and disease/medical history were recorded at entry. Sorafenib dosing and adverse events (AEs) were collected at follow‐up visits. The second interim analysis was undertaken when ~1500 treated patients were followed up for ≥ 4 months.
Results
Of the 1571 patients evaluable for safety, 61% had Child‐Pugh A status and 23% Child‐Pugh B. The majority of patients (74%) received the approved 800 mg initial sorafenib dose, regardless of Child‐Pugh status; however, median duration of therapy was shorter in Child‐Pugh B patients. The majority of drug‐related AEs were grade 1 or 2, and the most commonly reported were consistent with previous reports. The incidence and nature of drug‐related AEs were broadly similar across Child‐Pugh, Barcelona Clinic Liver Cancer (BCLC) and initial dosing subgroups, and consistent with the overall population.
Conclusions
Consistent with the first interim analysis, overall safety profile and dosing strategy are similar across Child‐Pugh subgroups. Safety findings also appear comparable irrespective of initial sorafenib dose or BCLC stage. Final analyses in > 3000 patients are ongoing.
Very few studies have explored the temporal relationship between hypertension and trigeminal neuralgia (TN). The aim of this population-based follow-up study was to investigate whether hypertension ...is associated with a higher risk of developing TN.
A total of 138,492 persons with at least 2 ambulatory visits with the principal diagnosis of hypertension in 2001 were enrolled in the hypertension group. The nonhypertension group consisted of 276,984 age- and sex-matched, randomly sampled subjects without hypertension. The 3-year TN-free survival rate and the cumulative incidence of TN were calculated using the Kaplan-Meier method. Cox proportional hazard regression was used to estimate the hazard ratio of TN.
In the hypertension group, 121 patients developed TN during follow-up, while, in the nonhypertension group, 167 subjects developed TN. The crude hazard ratio for the hypertension group was 1.52 (95% confidence interval CI 1.20-1.92; p = 0.0005), while, after adjustment for demographic characteristics and medical comorbidities, the adjusted hazard ratio was 1.51 (95% CI 1.19-1.90; p = 0.0006).
This study shows a significantly increased risk of developing TN after hypertension. Further studies are needed to elucidate the underlying mechanism of the association between hypertension and TN.
Systems that exhibit phase competition, order parameter coexistence, and emergent order parameter topologies constitute a major part of modern condensed-matter physics. Here, by applying a range of ...characterization techniques, and simulations, we observe that in PbTiO
/SrTiO
superlattices all of these effects can be found. By exploring superlattice period-, temperature- and field-dependent evolution of these structures, we observe several new features. First, it is possible to engineer phase coexistence mediated by a first-order phase transition between an emergent, low-temperature vortex phase with electric toroidal order and a high-temperature ferroelectric a
/a
phase. At room temperature, the coexisting vortex and ferroelectric phases form a mesoscale, fibre-textured hierarchical superstructure. The vortex phase possesses an axial polarization, set by the net polarization of the surrounding ferroelectric domains, such that it possesses a multi-order-parameter state and belongs to a class of gyrotropic electrotoroidal compounds. Finally, application of electric fields to this mixed-phase system permits interconversion between the vortex and the ferroelectric phases concomitant with order-of-magnitude changes in piezoelectric and nonlinear optical responses. Our findings suggest new cross-coupled functionalities.
Autophagy, a process for catabolizing cytoplasmic components, has been implicated in the modulation of interactions between RNA viruses and their host. However, the mechanism underlying the ...functional role of autophagy in the viral life cycle still remains unclear. Hepatitis C virus (HCV) is a single-stranded, positive-sense, membrane-enveloped RNA virus that can cause chronic liver disease. Here we report that HCV induces the unfolded protein response (UPR), which in turn activates the autophagic pathway to promote HCV RNA replication in human hepatoma cells. Further analysis revealed that the entire autophagic process through to complete autolysosome maturation was required to promote HCV RNA replication and that it did so by suppressing innate antiviral immunity. Gene silencing or activation of the UPR-autophagy pathway activated or repressed, respectively, IFN-β activation mediated by an HCV-derived pathogen-associated molecular pattern (PAMP). Similar results were achieved with a PAMP derived from Dengue virus (DEV), indicating that HCV and DEV may both exploit the UPR-autophagy pathway to escape the innate immune response. Taken together, these results not only define the physiological significance of HCV-induced autophagy, but also shed light on the knowledge of host cellular responses upon HCV infection as well as on exploration of therapeutic targets for controlling HCV infection.
Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose ...was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han‐Chinese patients without prior warfarin treatments. Using the genotype‐based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR >4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R2 of 0.62). This study demonstrated that pharmacogenetics‐based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.
Clinical Pharmacology & Therapeutics (2008); 84, 1, 83–89 doi:10.1038/sj.clpt.6100453
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