Background and purpose
White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) have been linked to small‐vessel disease, but the precise pathogenesis underlying WMHs remains unclear. ...Studies about an association of WMHs with extracranial atherosclerotic stenosis (ECAS) showed conflicting results and the relationship of WMHs with intracranial atherosclerotic stenosis (ICAS) is uncertain.
Methods
A cross‐sectional study of 679 consecutive Korean patients with acute ischaemic stroke (mean age 67.8 ± 12.6; 395 males) who underwent brain MRI/MR angiography was conducted. Severity of deep WMHs (d‐WMHs, n = 560) and periventricular WMHs (p‐WMHs, n = 590) was rated separately and compared across three groups: ICAS (n = 318), ECAS (n = 71) and no cerebral atherosclerotic stenosis (NCAS) (n = 290).
Results
The ICAS group showed a higher d‐WMH/p‐WMH score (1.62 ± 0.85/1.65 ± 0.79) than both the ECAS (1.25 ± 0.87/1.23 ± 0.78) and NCAS (1.19 ± 0.92/1.24 ± 0.81) groups (P < 0.001 for all). Patients with a greater number of ICAS were more likely to have higher scores of d‐WMH/p‐WMH (P < 0.001 for all). Patients with higher scores of d‐WMH/p‐WMH had a higher incidence of ICAS (P < 0.001 for all), but not of ECAS or NCAS. In multivariable analysis, a dose−response relationship was observed between the extent of ICAS versus WMHs. Compared with one ICAS lesion, for d‐WMHs the odds ratio (OR) = 2.61 95% confidence interval (CI) 0.95–7.20 for two ICAS lesions and OR = 3.37 (1.10–10.32) for ≥3 ICAS lesions; whilst for p‐WMHs (score ≥2) OR = 1.70 (95% CI 0.96–2.98) for two ICAS lesions and OR = 2.02 (1.15–3.55) for ≥3 ICAS lesions.
Conclusion
ICAS is independently associated with progressively greater WMH burden. The association of ICAS with WMH severity appears to be stronger than that of ECAS/NCAS in the Korean (Asian) stroke population.
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•Wide range of performance parameters were scanned for the optimal design space of a compact tokamak fusion reactor.•Novel computational algorithm to determine the optimum radial build was ...utilized.•Prospective design space was determined depending on the levels of physics and technology.
Using a novel computational algorithm that integrates tokamak systems analysis with neutron transport calculations, the minimum major radius (R0) and resulting maximum magnetic field at the plasma center (BT) can be determined uniquely for a given plasma performance. Plasma performance was varied extensively using a supercomputer (KAIROS) and scanning over a wide range of physics, technology, and system parameters to derive the optimal design space for a compact tokamak fusion reactor. Given the design goals of fusion gain Q > 20.0, net electric power > 100 MW, neutron wall loading < 2.0 MW/m2, indicator of divertor power handling PSOL/R0 < 25 MW/m, direct capital cost < $4.0 billion, and steady-state operation, a prospective design space was determined depending on the levels of physics and technology. Advanced engineering features, such as maximum allowable magnetic field at the toroidal field coil (Bmax = 23 T), were implemented by adopting high-temperature superconducting magnet technology, using an advanced shield material such as tungsten carbide (WC), and a plug-bucked magnet support structure. It was found that by exceeding the energy confinement scaling laws of IPB98y2, a design space of R0 < 4.0 m could be accessed under the following conditions for a conventional tokamak: confinement enhancement factor H > 1.7, bootstrap current fraction fBS > 0.55, magnetic field at the magnetic axis BT > 4.0 T, fusion power Pfusion > 600 MW, and thermodynamic efficiency ηth > 0.33. For a spherical tokamak, these conditions were H > 1.3, fBS > 0.6, BT 〈 6.0 T, and Pfusion 〉 500 MW. Sensitivity studies on the energy confinement scaling laws showed that stricter conditions on the physics parameters were required with the ITPA20 scaling law, whereas the conditions were mitigated with the β-independent scaling law.
spp., one of the most common foodborne bacterial pathogens, has the ability to survive under desiccation conditions in foods and food processing facilities for years. This raises the concerns of
...infection in humans associated with low water activity foods.
responds to desiccation stress via complex pathways involving immediate physiological actions as well as coordinated genetic responses. However, the exact mechanisms of
to resist desiccation stress remain to be fully elucidated. In this study, we screened a genome-saturating transposon (Tn5) library of
Typhimurium (
. Typhimurium) 14028s under the
desiccation stress using transposon sequencing (Tn-seq). We identified 61 genes and 6 intergenic regions required to overcome desiccation stress.
desiccation resistance genes were mostly related to energy production and conversion; cell wall/membrane/envelope biogenesis; inorganic ion transport and metabolism; regulation of biological process; DNA metabolic process; ABC transporters; and two component system. More than 20% of the
desiccation resistance genes encode either putative or hypothetical proteins. Phenotypic evaluation of 12 single gene knockout mutants showed 3 mutants (
, and
) had significantly (
< 0.02) reduced survival as compared to the wild type during desiccation survival. Thus, our study provided new insights into the molecular mechanisms utilized by
for survival against desiccation stress. The findings might be further exploited to develop effective control strategies against
contamination in low water activity foods and food processing facilities.
This paper proposes a novel pinning consensus method for nonlinear multi-agent systems (MASs) with node and edge betweenness centrality. The selection of pinned nodes and centrality analysis methods ...are introduced to explain a combined scheme. By utilizing the Lyapunov analysis, the conditions of the consensus criterion are derived from linear matrix inequality terms. Moreover, the combined consensus scheme results are given with one numerical example.
Fibroblast growth factor 21 (FGF21)-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1) levels in adipose tissues, suggesting that ...UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at reducing body weight and improving glucose homeostasis without UCP1. We find while FGF21 can lower body weight in both wild-type and Ucp1 knockout mice, rapid clearance of glucose by FGF21 is defective in the absence of UCP1. Furthermore, in obese wild-type mice there is a fall in brown adipose tissue (BAT) temperature during glucose excursion, and FGF21 improves glucose clearance while preventing the fall in BAT temperature. In Ucp1 knockout mice, the fall in BAT temperature during glucose excursion and FGF21-mediated changes in BAT temperature are lost. We conclude FGF21-mediated improvements in clearance of a glucose challenge require UCP1 and evoke UCP1-dependent thermogenesis as a method to increase glucose disposal.
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•FGF21 is equally effective at reducing body weight with or without UCP1•Improvement in clearance of a glucose load by FGF21 is lost in the absence of UCP1•FGF21 increases temperatures of BAT and body surface during glucose clearance•UCP1 is required for FGF21-mediated improvements in clearance of a glucose load
UCP1 was recently proposed as being dispensable for anti-obesity and anti-diabetic actions of FGF21. Kwon et al. show that FGF21 lowers body weight without UCP1. However, FGF21-mediated improvements in glucose clearance require UCP1 and correlate with increased temperature, pointing to thermogenesis as the mechanism of increased glucose disposal.
Vapor‐phase polymerization is used for the first time to prepare ultrathin, polycrystalline conducting films of poly(3,4‐ethylenedioxythiophene) (PEDOT). The polarized optical microscopy images (see ...figure) display the progress of crystalline growth at 30 °C: a) initial step of self‐assembled PEDOT film formation (amorphous shape); b) nucleation; c) crystalline growth; and d) dendritic growth. The scale is 100 × 100 μm2.
Modulating the DNA damage response and repair (DDR) pathways is a promising strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral inhibitor of the serine/threonine protein ...kinase ataxia telangiectasia and Rad3-related protein, which is crucial for DDR.
This phase II trial evaluated ceralasertib plus durvalumab for the treatment of patients with metastatic melanoma who had failed anti-programmed cell death protein 1 therapy.
Among the 30 patients, we observed an overall response rate of 31.0% and a disease control rate of 63.3%. Responses were evident across patients with acral, mucosal, and cutaneous melanoma. The median duration of response was 8.8 months (range, 3.8-11.7 months). The median progression-free survival was 7.1 months (95% confidence interval, 3.6-10.6 months), and the median overall survival was 14.2 months (95% confidence interval, 9.3-19.1 months). Common adverse events were largely hematologic and manageable with dose interruptions and reductions. Exploratory biomarker analysis suggested that tumors with an immune-enriched microenvironment or alterations in the DDR pathway were more likely to respond to the study treatment.
We conclude that ceralasertib in combination with durvalumab has promising antitumor activity among patients with metastatic melanoma who have failed anti-programmed cell death protein 1 therapy, and constitute a population with unmet needs.
•Combination of ceralasertib and durvalumab had a tolerable safety profile in patients with metastatic melanoma.•Combination treatment resulted in median progression-free survival of 7.1 months and median overall survival of 14.2 months.•Our data suggest that this combination could be used to salvage patients with immunotherapy-resistant melanoma.•Ceralasertib plus durvalumab is worthy of further investigation for melanoma after failure of frontline immunotherapy.
Background
Postoperative pancreatic fistula (POPF) remains a major cause of morbidity after distal pancreatectomy. The aim of this study was to investigate whether duct‐to‐mucosa ...pancreaticogastrostomy of the pancreatic stump decreased clinical POPF formation compared with handsewn closure after distal pancreatectomy.
Methods
This multicentre RCT was performed between April 2012 and June 2014. Patients undergoing distal pancreatectomy were assigned randomly to either duct‐to‐mucosa pancreaticogastrostomy or handsewn closure. The primary endpoint was the incidence of clinical POPF. Secondary endpoints were rates of other complications and length of hospital stay.
Results
Some 80 patients were randomized, and 73 patients were evaluated in an intention‐to‐treat analysis: 36 in the pancreaticogastrostomy group and 37 in the handsewn closure group. The duration of operation was significantly longer in the pancreaticogastrostomy group than in the handsewn closure group (mean 268 versus 197 min respectively; P < 0·001). The incidence of clinical POPF did not differ between groups (7 of 36 versus 7 of 37; odds ratio (OR) 1·03, 95 per cent c.i. 0·32 to 3·10; P = 1·000). The rate of intra‐abdominal fluid collection was significantly lower in the pancreaticogastrostomy group (6 of 36 versus 21 of 37; OR 0·15, 0·05 to 0·45; P < 0·001). There were no statistically significant differences in the rates of other complications or length of hospital stay.
Conclusion
Duct‐to‐mucosa pancreaticogastrostomy did not reduce the incidence of clinical POPF compared with handsewn closure of the pancreatic stump after distal pancreatectomy. Registration number UMIN000007426 (http://www.umin.ac.jp).
Pancreatic fistula rate similar
A new object tracking mask-based novel-look-up-table (OTM-NLUT) method is proposed and implemented on graphics-processing-units (GPUs) for real-time generation of holographic videos of ...three-dimensional (3-D) scenes. Since the proposed method is designed to be matched with software and memory structures of the GPU, the number of compute-unified-device-architecture (CUDA) kernel function calls and the computer-generated hologram (CGH) buffer size of the proposed method have been significantly reduced. It therefore results in a great increase of the computational speed of the proposed method and enables real-time generation of CGH patterns of 3-D scenes. Experimental results show that the proposed method can generate 31.1 frames of Fresnel CGH patterns with 1,920 × 1,080 pixels per second, on average, for three test 3-D video scenarios with 12,666 object points on three GPU boards of NVIDIA GTX TITAN, and confirm the feasibility of the proposed method in the practical application of electro-holographic 3-D displays.
Summary
Thyroid dysfunction is associated with the loss of bone density (osteoporosis). However, the connection between subclinical thyroid dysfunction and osteoporosis remains controversial. This ...study found no apparent association between subclinical hypothyroidism or subclinical hyperthyroidism and bone mineral density (BMD) in the lumbar spine and femur.
Introduction
The present study examined the relationship between subclinical thyroid dysfunction and BMD in healthy middle-aged adults.
Methods
A total of 25,510 healthy Koreans with normal free thyroxine levels were enrolled from January 2011 to December 2016, and 91% of subjects visited only once. The average age of the 15,761 women was 45, and the average age of the 9749 men was 48. Levels of thyroid-stimulating hormone (TSH) and BMD were recorded in all subjects. BMD was measured using dual-energy X-ray absorptiometry.
Results
No apparent association was found between subclinical thyroid dysfunction and BMD in the lumbar spine, femur-neck, and proximal femur sites compared with a euthyroid group. Age, body mass index (BMI), and postmenopausal status affected BMD in women, and only BMI affected BMD in men. Subclinical hypothyroidism was independently associated with a lower risk of osteoporosis (odds ratio 0.657, 95% confidence interval 0.464–0.930) in 4710 postmenopausal women.
Conclusions
No apparent association was found between subclinical hypothyroidism or subclinical hyperthyroidism defined on single TSH measurement and BMD at the lumbar spine and femur in a large cohort of middle-aged men and women. Subclinical hypothyroidism was independently associated with a lower risk of osteoporosis in postmenopausal women.
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