In this prospective study, Han Chinese subjects who were candidates for carbamazepine therapy were screened for the HLA-B*1502 allele because of its association with the Stevens–Johnson syndrome and ...toxic epidermal necrolysis.
The Stevens–Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), are two of the most serious adverse reactions caused by drugs. SJS is characterized by high fever, malaise, and a rapidly developing, blistering exanthema of macular papules and target-like lesions, accompanied by mucosal involvement. This condition is associated with a rate of death of approximately 5%. TEN has a similar presentation, with even more extensive skin detachment and a death rate of 25 to 35%.
1
Carbamazepine, an anticonvulsant and specific analgesic agent for trigeminal neuralgia, is the most common cause of SJS–TEN in Southeast Asian countries.
2
We previously . . .
Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy ...composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 μm) and ultra-fine grains (0.5∼2 μm), together with heterogeneous L1
-structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L1
nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.
Alloy design based on single-principal-element systems has approached its limit for performance enhancements. A substantial increase in strength up to gigapascal levels typically causes the premature ...failure of materials with reduced ductility. Here, we report a strategy to break this trade-off by controllably introducing high-density ductile multicomponent intermetallic nanoparticles (MCINPs) in complex alloy systems. Distinct from the intermetallic-induced embrittlement under conventional wisdom, such MCINP-strengthened alloys exhibit superior strengths of 1.5 gigapascals and ductility as high as 50% in tension at ambient temperature. The plastic instability, a major concern for high-strength materials, can be completely eliminated by generating a distinctive multistage work-hardening behavior, resulting from pronounced dislocation activities and deformation-induced microbands. This MCINP strategy offers a paradigm to develop next-generation materials for structural applications.
Summary Background A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy ...to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy. Methods We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov , and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis. Findings We analysed data from 19 trials and 4806 patients. Median follow-up was 7·7 years (IQR 6·2–11·9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio HR 0·79, 95% CI 0·73–0·86, p<0·0001; absolute benefit at 5 years 6·3%, 95% CI 3·5–9·1). The interaction between treatment effect (benefit of chemotherapy) on overall survival and the timing of chemotherapy was significant (p=0·01) in favour of concomitant plus adjuvant chemotherapy (HR 0·65, 0·56–0·76) and concomitant without adjuvant chemotherapy (0·80, 0·70–0·93) but not adjuvant chemotherapy alone (0·87, 0·68–1·12) or induction chemotherapy alone (0·96, 0·80–1·16). The benefit of the addition of chemotherapy was consistent for all endpoints analysed (all p<0·0001): progression-free survival (HR 0·75, 95% CI 0·69–0·81), locoregional control (0·73, 0·64–0·83), distant control (0·67, 0·59–0·75), and cancer mortality (0·76, 0·69–0·84). Interpretation Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed. Funding French Ministry of Health (Programme d'actions intégrées de recherche VADS), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.
A discrete degree of freedom can be engineered to match the Hamiltonian of particles moving in a real-space lattice potential. Such synthetic dimensions are powerful tools for quantum simulation ...because of the control they offer and the ability to create configurations difficult to access in real space. Here, in an ultracold
Sr atom, we demonstrate a synthetic-dimension based on Rydberg levels coupled with millimeter waves. Tunneling amplitudes between synthetic lattice sites and on-site potentials are set by the millimeter-wave amplitudes and detunings respectively. Alternating weak and strong tunneling in a one-dimensional configuration realizes the single-particle Su-Schrieffer-Heeger (SSH) Hamiltonian, a paradigmatic model of topological matter. Band structure is probed through optical excitation from the ground state to Rydberg levels, revealing symmetry-protected topological edge states at zero energy. Edge-state energies are robust to perturbations of tunneling-rates that preserve chiral symmetry, but can be shifted by the introduction of on-site potentials.
Aim
Pregnant women have been recommended to take FA daily to prevent birth defects in the brain and spinal cord. We previously showed that folic acid (FA) exerts an anti‐angiogenic activity. As ...angiogenesis is important for endometrial reorganization and embryonic development, there should be some mechanisms to allow the pregnant mother and the foetus to escape from the FA‐induced anti‐angiogenesis. This study was designed to investigate the effect of female sex hormones on the FA‐induced anti‐angiogenic activity.
Methods
The protein levels and protein‐protein interaction were examined by Western blot analysis and immunoprecipitation assay respectively. The cell proliferation and migration were examined by MTT assay and wound healing assay respectively. The in vivo angiogenesis was evaluated by Matrigel angiogenesis assay.
Results
In human umbilical venous endothelial cells (HUVEC), FA receptor (FR) formed a complex with progesterone receptor (PR), oestradiol receptor (ER) and cSrc. Pregnancy levels of progesterone (P4) or oestradiol (E2) prevented FA‐induced inhibitions of proliferation and migration in HUVEC. Both E2 and P4 prevented the FA‐induced anti‐angiogenesis in vivo. Moreover, cotreatment with FA and P4 or E2 inhibited the signalling pathways involved in FA‐induced inhibitions of proliferation and migration in HUVEC.
Conclusion
Female sex hormones interrupt the FA‐induced anti‐angiogenic action through receptor‐receptor interaction.
Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities.
To address the impact of neuropsychiatric symptoms ...of patients in different stages of AD on their caregivers' burden.
This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center.
All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI.
The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively).
The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.
The amorphous nature of metallic glasses and their mechanical properties make them interesting for structural applications. However, the interplay between the nature of atomic structures in metallic ...glasses and mechanical properties remains poorly understood. In this study, high-frequency dynamic micropillar tests have been used to probe both atomic clusters and flow defects in metallic glasses. We show that loosely bonded atomistic free-volume zones that are enveloped elastically by tightly bonded atomic clusters show a deformation character similar to supercooled liquids. At room temperature, the effective viscosity of these free-volume zones is of the order of 1×108 Pa s before the occurrence of shear banding. The confined liquid-like deformation of free-volume zones leads to significant mechanical hysteresis in micropillars under dynamic loading, providing important insight into how atomistic structural features affect the deformation behaviours in metallic glasses in the apparent elastic regime. The inelastic behaviour also serves as the basis for the superior damping resistance of metallic glasses.
Many novel properties of non-Hermitian systems are found at or near the exceptional points-branch points of complex energy surfaces at which eigenvalues and eigenvectors coalesce. In particular, ...higher-order exceptional points can result in optical structures that are ultrasensitive to external perturbations. Here we show that an arbitrary order exceptional point can be achieved in a simple system consisting of identical resonators placed near a waveguide. Unidirectional coupling between any two chiral dipolar states of the resonators mediated by the waveguide mode leads to the exceptional point, which is protected by the transverse spin-momentum locking of the guided wave and is independent of the positions of the resonators. Various analytic response functions of the resonators at the exceptional points are experimentally manifested in the microwave regime. The enhancement of sensitivity to external perturbations near the exceptional point is also numerically and analytically demonstrated.
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