Summary
Objectives
To review clinical evidence on the antiepileptic effects of deep brain stimulation (DBS) for drug‐resistant epilepsy, its safety, and the factors influencing individual outcomes.
...Methods
A comprehensive search of the medical literature (PubMed, Medline) was conducted to identify relevant articles investigating DBS therapy for drug‐resistant epilepsy. Reference lists of these articles were used to source further articles.
Results
Stimulation of the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to decrease the frequency of refractory seizures. Half of all patients from clinical studies experienced a 46%‐90% seizure reduction with ANT‐DBS, and a 48%‐95% seizure reduction with HC‐DBS. The efficacy of stimulating other targets remains inconclusive due to lack of evidence. Approximately three‐fourths of patients receiving ANT, HC, or centromedian nucleus of the thalamus (CMT) stimulation are responders—experiencing a seizure reduction of at least 50%. The time course of clinical benefit varies dramatically, with both an initial lesional effect and ongoing stimulation effect at play. Improved quality of life and changes to cognition or mood may also occur. Side effects are similar in nature to those reported from DBS therapy for movement disorders. Several factors are potentially associated with stimulation efficacy, including an absence of structural abnormality on imaging for ANT and HC stimulation, and electrode position relative to the target. Certain seizure types or syndromes may respond more favorably to specific targets, including ANT stimulation for deep temporal or limbic seizures, and CMT stimulation for generalized seizures and Lennox‐Gastaut syndrome.
Significance
We have identified several patient, disease, and stimulation factors that potentially predict seizure outcome following DBS. More large‐scale clinical trials are needed to explore different stimulation parameters, reevaluate the indications for DBS, and identify robust predictors of patient response.
Abstract Background Our previous study results indicated that conversion from twice-daily Prograf to once-daily Advagraf associated with lower variability of tacrolimus blood trough level. Some ...factors, such as frequency of interaction by food exposure, expression of cytochrome P450 3A5 genetic polymorphism, and other interactions of unknown factors, could be the reasons for the change of variability. We aimed to clarify the impact of cytochrome P450 3A5 genetic polymorphism on the variability of tacrolimus blood trough level in Taiwanese kidney transplant recipients. Methods We collected blood samples from kidney transplant recipients to prepare DNA and then performed single-nucleotide polymorphism genotyping by using the restriction fragment length polymorphism. Results We found that 79 (52.7%) of 150 kidney transplant recipients had the low-expressive genotype (CYP3A5*3/*3), whereas the other 71 (47.3%) kidney transplant recipients had high-expressive genotype (CYP3A5*1/*1 and CYP3A5*1/*3). The prevalence of high-expressive genotype is higher than previous reports from western countries. Compared with the patients with high-expressive genotype, the average dose-normalized trough level of tacrolimus was significantly higher in patients with low-expressive genotype. Interestingly, when patients converted from twice-daily Prograf to once-daily Advagraf, the percent coefficient of variation of tacrolimus trough level was significantly decreased in patients with high-expressive genotype. Conclusion This study suggested that there is a potential benefit for kidney transplant recipients with cytochrome P450 3A5 high-expressive genotype (*1/*1 or *1/*3) to convert from Prograf to once-daily Advagraf.
The strong coupling between antiferromagnetism and ferroelectricity at room temperature found in BiFeO3 generates high expectations for the design and development of technological devices with novel ...functionalities. However, the multi-domain nature of the material tends to nullify the properties of interest and complicates the thorough understanding of the mechanisms that are responsible for those properties. Here we report the realization of a BiFeO3 material in thin film form with single-domain behaviour in both its magnetism and ferroelectricity: the entire film shows its antiferromagnetic axis aligned along the crystallographic b axis and its ferroelectric polarization along the c axis. With this we are able to reveal that the canted ferromagnetic moment due to the Dzyaloshinskii-Moriya interaction is parallel to the a axis. Furthermore, by fabricating a Co/BiFeO3 heterostructure, we demonstrate that the ferromagnetic moment of the Co film does couple directly to the canted moment of BiFeO3.
Summary
A growing elderly population is expected worldwide, and the burden of hip fractures on health care system will continue to increase. By 2035, there will be a 2.7-fold increase in the number ...of hip fractures in Taiwan. The study provides quantitative basis for the future distribution of medical resources.
Introduction
Hip fractures have long been recognized as a major public health concern. The study aimed to determine time trends in the incidence of hip fractures and to forecast the number of hip fractures expected in Taiwan up to 2035.
Methods
A nationwide survey was conducted using data from the Taiwan National Health Insurance Research Database from 2004 to 2011. A total of 141,397 hip fractures were identified, with a mean of 17,675 fractures/year. Annual incidences of hip fractures were calculated and tested for trends. Projections of the incidence rates of hip fractures and bed days associated with hip fractures were calculated using Poisson regression on the historical incidence rates in combination with population projections from 2012 to 2035.
Results
The incidence rates of hip fracture during 2004–2011 were 317 and 211 per 100,000 person-years among women and men, respectively. Over this 8-year period, the age-standardized incidence of hip fracture decreased by 13.4 % among women and 12.2 % among men. Despite the decline in the age-standardized incidence, the absolute number of hip fractures increased owing to the aging population. The number of hip fractures is expected to increase from 18,338 in 2010 to 50,421 in 2035—a 2.7-fold increase. The number of bed days for 2010 and 2035 was estimated at 161,248 and 501,995, respectively, representing a 3.1-fold increase.
Conclusions
The socioeconomic impact of hip fractures will be high in the near future. This study provides a quantitative basis for future policy decisions to serve this need.
The evolutions of MHD instability behaviors and enhancement of both electrostatic and electromagnetic turbulence towards the plasma disruption have been clearly observed in the HL-2A plasmas. Two ...types of plasma disruptive discharges have been investigated for similar equilibrium parameters: one with a distinct stage of a small central temperature collapse (Formula: see text 5-10%) around 1 millisecond before the thermal quench (TQ), while the other without. For both types, the TQ phase is preceded by a rotating 2/1 tearing mode, and it is the development of the cold bubble from the inner region of the 2/1 island O-point along with its inward convection that causes the massive energy loss. In addition, the micro-scale turbulence, including magnetic fluctuations and density fluctuations, increases before the small collapse, and more significantly towards the TQ. Also, temperature fluctuations measured by electron cyclotron emission imaging enhances dramatically at the reconnection site and expand into the island when approaching the small collapse and TQ, and the expansion is more significant close to the TQ. The observed turbulence enhancement near the X-point cannot be fully interpreted by the linear stability analysis by GENE. Evidences suggest that nonlinear effects, such as the reduction of local Formula: see text shear and turbulence spreading, may play an important role in governing turbulence enhancement and expansion. These results imply that the turbulence and its interaction with the island facilitate the stochasticity of the magnetic flux and formation of the cold bubble, and hence, the plasma disruption.
In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is ...associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload. It was a retrospective observational study. 101 patients with TDT were recruited for lung function tests. The most recent ferritin levels (pmol/L) and the magnetic resonance imaging (MRI) measurements of the myocardial and liver iron status, as measured by heart and liver T2* relaxation time (millisecond, ms) respectively, were retrieved from the computerized medical records. Only data within 12 months from the lung function measurement were included in the analysis. The serum ferritin, and the cardiac and liver T2* relaxation time were the surrogate indexes of body iron content. The threshold of abnormality in lung function was defined as under 80% of the predicted value. 101 subjects were recruited with a mean age of 25.1 years (standard deviation (SD) 7.9 years). Thirty-eight (38%) and five (5%) demonstrated restrictive and obstructive lung function deficits, respectively. A weak correlation of FVC %Predicted and TLC %Predicted with MRI myocardial T2* relaxation time (rho = 0.32, p = 0.03 and rho = 0.33, p = 0.03 respectively) was observed. By logistic regression, MRI cardiac T2* relaxation time was negatively associated with restrictive lung function deficit (B - 0.06; SE 0.03; Odds ratio 0.94; 95% confidence interval (CI) 0.89-0.99; p = 0.023) after adjusting for age, sex and body mass index. Restrictive pulmonary function deficit was commonly observed in patients with TDT, and the severity potentially correlates with myocardial iron content. Monitoring of lung function in this group of patients, particularly for those with iron overload, is important.
EGFR overexpression and chromosome 3p deletion are two frequent events in head and neck cancers. We previously mapped the smallest region of recurrent copy-number loss at 3p12.2-p14.1. LRIG1, a ...negative regulator of EGFR, was found at 3p14, and its copy-number loss correlated with poor clinical outcome. Inducible expression of LRIG1 in head and neck cancer TW01 cells, a line with low LRIG1 levels, suppressed cell proliferation in vitro and tumor growth in vivo. Gene expression profiling, quantitative RT-PCR, chromatin immunoprecipitation, and western blot analysis demonstrated that LRIG1 modulated extracellular matrix (ECM) remodeling and EGFR-MAPK-SPHK1 transduction pathway by suppressing expression of EGFR ligands/activators, MMPs and SPHK1. In addition, LRIG1 induction triggered cell morphology changes and integrin inactivation, which coupled with reduced SNAI2 expression. By contrast, knockdown of endogenous LRIG1 in TW06 cells, a line with normal LRIG1 levels, significantly enhanced cell proliferation, migration and invasiveness. Such tumor-promoting effects could be abolished by specific MAPK or SPHK1 inhibitors. Our data suggest LRIG1 as a tumor suppressor for head and neck cancers; LRIG1 downregulation in cancer cells enhances EGFR-MAPK-SPHK1 signaling and ECM remodeling activity, leading to malignant phenotypes of head and neck cancers.
Abstract
The interactions between electrons and antiferromagnetic magnons (AFMMs) are important for a large class of correlated materials. For example, they are the most plausible pairing glues in ...high-temperature superconductors, such as cuprates and iron-based superconductors. However, unlike electron-phonon interactions (EPIs), clear-cut observations regarding how electron-AFMM interactions (EAIs) affect the band structure are still lacking. Consequently, critical information on the EAIs, such as its strength and doping dependence, remains elusive. Here we directly observe that EAIs induce a kink structure in the band dispersion of Ba
1−
x
K
x
Mn
2
As
2
, and subsequently unveil several key characteristics of EAIs. We found that the coupling constant of EAIs can be as large as 5.4, and it shows strong doping dependence and temperature dependence, all in stark contrast to the behaviors of EPIs. The colossal renormalization of electron bands by EAIs enhances the density of states at Fermi energy, which is likely driving the emergent ferromagnetic state in Ba
1−
x
K
x
Mn
2
As
2
through a Stoner-like mechanism with mixed itinerant-local character. Our results expand the current knowledge of EAIs, which may facilitate the further understanding of many correlated materials where EAIs play a critical role.
Abstract CDEX-50 is a next-generation project of the China Dark Matter Experiment (CDEX) that aims to search for dark matter using a 50-kg germanium detector array. This paper comprises a thorough ...summary of the CDEX-50 dark matter experiment, including an investigation of potential background sources and the development of a background model. Based on the baseline model, the projected sensitivity of weakly interacting massive particle (WIMP) is also presented. The expected background level within the energy region of interest, set to 2–2.5 keVee, is ∼0.01 counts keVee -1 kg -1 day -1 . At 90% confidence level, the expected sensitivity to spin-independent WIMP-nucleon couplings is estimated to reach a cross-section of 5.1 × 10 -45 cm 2 for a WIMP mass of 5 GeV/c 2 with an exposure objective of 150 kg·year and an analysis threshold of 160 eVee. This science goal will correspond to the most sensitive results for WIMPs with a mass of 2.2–8 GeV/c 2 .
Active asteroids are those that show evidence of ongoing mass loss. We report repeated instances of particle ejection from the surface of (101955) Bennu, demonstrating that it is an active asteroid. ...The ejection events were imaged by the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer) spacecraft. For the three largest observed events, we estimated the ejected particle velocities and sizes, event times, source regions, and energies. We also determined the trajectories and photometric properties of several gravitationally bound particles that orbited temporarily in the Bennu environment. We consider multiple hypotheses for the mechanisms that lead to particle ejection for the largest events, including rotational disruption, electrostatic lofting, ice sublimation, phyllosilicate dehydration, meteoroid impacts, thermal stress fracturing, and secondary impacts.
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