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Laser interaction with an ultra-thin pre-structured target is investigated with the help of both two-dimensional and three-dimensional particle-in-cell simulations. With the existence of a periodic structure on the target surface, the laser seems to penetrate through the target at its fundamental frequency even if the plasma density of the target is much higher than the laser’s relativistically critical density. The particle-in-cell simulations show that the transmitted laser energy behind the pre-structured target is increased by about two orders of magnitude compared to that behind the flat target. Theoretical analyses show that the transmitted energy behind the pre-structured target is actually re-emitted by electron ‘islands’ formed by the surface plasma waves on the target surfaces. In other words, the radiation with the fundamental frequency is actually ‘surface emission’ on the target rear surface. Besides the intensity of the component with the fundamental frequency, the intensity of the high-order harmonics behind the pre-structured target is also much enhanced compared to that behind the flat target. The enhancement of the high-order harmonics is also related to the surface plasma waves generated on the target surfaces.
Abnormal Ca homeostasis has been associated with impaired glucose metabolism. However, the epidemiological evidence is controversial. We aimed to assess the association between circulating Ca levels and the risk of type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis through conducting a systematic review and meta-analysis. Eligible studies were identified by searching electronic database (PubMed, Embase and Google Scholar) and related references with de novo results from primary studies up to December 2018. A random-effects meta-analysis was performed to estimate the weighted relative risks (RR) and 95 % CI for the associations. The search yielded twenty eligible publications with eight cohort studies identified for the meta-analysis, which included a total of 89 165 participants. Comparing the highest with the lowest category of albumin-adjusted serum Ca, the pooled RR was 1·14 (95 % CI 1·05, 1·24) for T2DM (n 51 489). Similarly, serum total Ca was associated with incident T2DM (RR 1·25; 95 % CI 1·10, 1·42) (n 64 502). Additionally, the adjusted RR for 1 mg/dl increments in albumin-adjusted serum Ca or serum total Ca levels was 1·16 (95 % CI 1·07, 1·27) and 1·19 (95 % CI 1·11, 1·28), respectively. The observed associations remained with the inclusion of a cohort study with ionised Ca as the exposure. However, data pooled from neither case–control (n 4) nor cross-sectional (n 8) studies manifested a significant correlation between circulating Ca and glucose homeostasis. In conclusion, accumulated data from the cohort studies suggest that higher circulating Ca levels are associated with an augmented risk of T2DM.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Background: The Endoscopic endonasal approach (EEA) has been gaining popularity in the past decade as an alternative to traditional transcranial and transorbital approaches. We have performed orbital apex decompression for a variety of pathological entities. Methods: We performed a retrospective chart review on patients who underwent EEA orbital apex decompression between January 1st 2010 and December 1st 2018 at McMaster University. Results: Eight patients underwent endoscopic endonasal orbital decompression at our center, including five male patients and three female patients. The mean age of our patients was 50.1 years. The different pathologies we treated included nasopharyngeal carcinoma, hemangioma, fibrous dysplasia, IgG4 disease, inverted papilloma, angioleiomyoma, and neuroendocrine paraganglioma. Five patients presented with visual symptoms. Postoperatively, one of these five patients improved to baseline, three had stable vision, another one had progressive visual decline despite surgical intervention. Conclusions: Endoscopic endonasal approach can be used as an alternative to decompress orbital apex pathologies in selected patients.
Background: The Endoscopic endonasal approach (EEA) has become increasingly popular in the treatment of suprasellar meningiomas, which often cause visual symptoms due to compression of the anterior optic apparatus. Methods: We performed a retrospective chart review on patients who underwent EEA optic nerve decompression and resection of suprasellar meningiomas between January 1st 2005 and December 1st 2018 at McMaster University. Results: The mean age of our patients was 59.8 years. We treated 9 male and 23 female patients, with a mean follow up of 6.29 years. 23 patients (71.9%) presented with visual symptoms, with a mean duration of 8.65 months. In our patient cohort, 95.5% had stable or improved visual acuity postoperatively. Less than six months of visual decline was more likely to be associated with postoperative improvement of visual acuity, with an odds ratio (OR) of 0.0222 (95% CI: 0.0017–0.289, p<0.05); as well as visual field (OR:0.0625; 95% CI, 0.0042–0.915, p<0.05). Additionally, the absence of RAPD was associated with improved postoperative visual acuity (OR: 0.0675; 95% CI, 0.0354–0.706, p<0.05). Conclusions: Endoscopic endonasal approach can achieve good visual outcome in patients harboring suprasellar meningiomas. Symptom duration of less than six months and absence of RAPD were positive predictor of postoperative visual outcome.
Background: Central neurocytoma’s are typically located in the lateral ventricles and are optimally treated with surgical resection. Surgical entry into the ventricles are associated with a number of complications, including subdural hygroma and shunt-dependent hydrocephalus. Methods: We report a patient who developed acute bilateral uncal herniation from progessively enlarging subdural hygromas following intraventricular tumour resection. Results: A 60-year-old female underwent minimally invasive transcortical transventricular resection of an intraventricular CN. The patient’s postoperative course was complicated by repeated presentations to the emergency department due to persistent and intractable nausea and headaches, without focal neurological deficits. Imaging demonstrated small bilateral subdural hygromas. The patient eventually presented with acute deterioration in her level of consciousness with clinical and radiologic evidence of bilateral uncal herniation, requiring urgent insertion of a subdural drain to treat elevated intracranial pressure (ICP). After insertion of a ventriculoperitoneal shunt, the patient was discharged in stable condition and is currently followed by the multi-disciplinary neuro-oncology team. Conclusions: Bilateral subdural hygroma could mask underlying external hydrocephalus post transventricular surgeries. Patients who are symptomatic from bilateral subdural hygromas after transventricular resection of tumors should be carefully monitored for radiographic or clinical progression, in order to avoid acute deterioration caused by elevated ICP.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
Recent work has implicated one type of horizontal strabismus (exotropia) as a risk factor for schizophrenia. This new insight raises questions about a potential common developmental origin of the two diseases. Seasonality of births is well established for schizophrenia. Seasonal factors such as light exposure affect eye growth and can cause vision abnormalities, but little is known about seasonality of births in strabismus. We examined birth seasonality in people with horizontal strabismus in a retrospective study in Washoe County, Nevada, and re-examined similar previously obtained data from Osaka, Japan. We then compared seasonal patterns of births between strabismus, refractive error, schizophrenia and congenital toxoplasmosis. Patients with esotropia had a significant seasonality of births, with a deficit in March, then increasing to an excess in September, while patients with exotropia had a distinctly different pattern, with an excess of births in July, gradually decreasing to a deficit in November. These seasonalities were statistically significant with either χ2 or Kolmogorov–Smirnov-type statistics. The birth seasonality of esotropia resembled that for hyperopia, with an increase in amplitude, while the seasonality for myopia involved a phase-shift. There was no correlation between seasonality of births between strabismus and congenital toxoplasmosis. The pattern of an excess of summer births for people with exotropia was remarkably similar to the well-established birth seasonality of one schizophrenia subtype, the deficit syndrome, but not schizophrenia as a whole. This suggests a testable hypothesis: that exotropia may be a risk factor primarily for the deficit type of schizophrenia.
In several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent. To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017. Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities. Here strong association between rs12252 and influenza was found in all four genetic models. The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03–1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39–33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking. Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08–1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08–2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36–5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals. Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.
Didymocarpus middletonii Souvann., Soulad. & Tagane, a new species of Gesneriaceae from Nam Kading National Protected Area, is described and illustrated. The new species is morphologically similar to Didymocarpus brevicalyx, D. formosus and D. puhoatensis but distinguished from the three by its fewer-flowered inflorescence, longer pedicel, and urceolate and multicellular eglandular hairy calyx. Based on the latest IUCN criteria, Didymocarpus middletonii is proposed to be Critically Endangered (CR). Our record of Didymocarpus represents a new genus record for the flora of Laos.
Because of rapid solidification involved in the laser or e-beam based additive manufacturing (AM) process, solution treatable metallic parts made by these methods usually possess a unique nonequilibrium microstructure which changes significantly during subsequent thermal treatment. Such evolution alters the size, morphology, length scale, and distribution of microstructural features and has a substantial impact on thermal properties and possibly on electrical properties as well. This study focuses on effects of microstructural evolution on thermal properties of an additively manufactured AlSi10Mg part. The changes of thermal properties such as thermal expansion, heat capacity, thermal diffusivity, and thermal conductivity as a function of thermal treatment are reported. The results show that the formation of supersaturated primary α aluminum and unique cellular structure imparted by fast solidification in the AM process are the major cause for the low thermal diffusivity and low thermal conductivity observed in this solution treatable, as-built part. A correlation between microstructural evolution and changes in thermal properties is established. Advantages and tailoring of the thermal properties of additively built parts are discussed. Implications of these results are important for other additively manufactured components based on popular solution treatable alloys.
Environment can impact the wear behavior of metals and alloys substantially. The tribological properties of Al0.6CoCrFeNi high-entropy alloys (HEAs) were investigated in ambient air, deionized water, simulated acid rain, and simulated seawater conditions at frequencies of 2–5 Hz. The as-cast alloy was composed of simple face-centered cubic and body-centered cubic phases. The wear rate of the as-cast HEA in the ambient air condition was significantly higher than that in the liquid environment. The wear resistance in seawater was superior to that in ambient air, deionized water, and acid rain. Both the friction coefficient and wear rate in seawater were the lowest due to the formation of oxidation film, lubrication, and corrosion action in solution. The dominant wear mechanism in the ambient air condition and deionized water was abrasive wear, delamination wear, and oxidative wear. By contrast, the wear mechanism in acid rain and seawater was mainly corrosion wear, adhesive wear, abrasive wear, and oxidative wear.
Hemostasis, a process which causes bleeding to stop, can be enhanced using chitosan; but the detailed mechanism is unclear. Red blood cells (RBCs) adhere to chitosan because of their opposite charges, but the adhesion force is small, 3.83 pN as measured here using an optical tweezer, such that the direct adhesion cannot be the sole cause for hemostasis. However, it was observed in this study that layer structures of aggregated RBCs were formed next to chitosan objects in both static and flowing environments, but not formed next to cotton and rayon yarns. The layer structure is the clue for the initiation of hemostatsis. Through the supporting measurements of zeta potentials of RBCs and pH's using blood-chitosan mixtures, it is proposed here that the formation of the RBC layer structure next to chitosan objects is due to the reduction of repulsive electric double layer force between RBCs, because of the association of H+ deprotonated from chitosan with COO− on RBC membrane, under the DLVO (Derjaguin-Landau-Verwey-Overbeek) theory. The results are beneficial for designing effective chitosan-based wound dressings, and also for general biomedical applications.
Full-scale simulations of a (Magnetorheological) MR damper are carried out for revealing its hysteretic behaviors associated with implementation of semi-active control using the routine of computational fluid dynamics. By virtue of the structural symmetry of the MR damper, a two-dimensional configuration for finite element simulation is built up. Herschel-Bulkley model is employed to represent the property of the MR fluid, of which the control parameters and their relevances to the input current are addressed. Typical cases involving sinusoidal and irregular displacements, steady and transient currents loaded upon the MR damper are investigated. Numerical investigations reveal that the damper force has a positive correlation with input current, excitation amplitude and excitation frequency. The full-scale simulation is proved to exhibit a sound accuracy through the validation of experimental data. It provides a logical manner revealing the true performance of MR dampers under desirable operating modes in practice, and can be readily integrated with the gain design of the associated semi-actively controlled structure. This progress bypasses the technical challenge inherent in the traditional tests with low-frequency cyclic loadings due to the limitation of experimental setup. Besides, comparative study between two-dimensional and three-dimensional configuration simulations of the MR damper shows that former has a better applicability, which can be carried out on a low-cost platform.
Good canopy structure is essential for optimal maize (Zea mays L.) production. However, creating appropriate maize canopy structure can be difficult, because the characteristics of individual plants are altered by changes in plant age, density and interactions with neighbouring plants. The objective of the current study was to find a reliable method for building good maize canopy structure by analysing changes in canopy structure, light distribution and grain yield (GY). A modern maize cultivar (ZhengDan958) was planted at 12 densities ranging from 1.5 to 18 plants/m2 at two field locations in Xinjiang, China. At the silking stage (R1), plant and ear height increased with plant density as well as leaf area index (LAI), whereas leaf area per plant decreased logarithmically. The fraction of light intercepted by the plant (F) increased with increasing plant density, but the light extinction coefficient (K) decreased linearly from 0.61 to 0.39. Taking the optimum value of F (95%) as an example, and using measured values of K for each plant density at R1 and the equation from Beer's law, the corresponding (theoretical) LAI for each plant density was calculated and optimum plant density (9.72 plants/m2) obtained by calculating the difference between theoretical LAIs and actual observations. Further analysis showed that plant density ranging from 10.64 to 11.55 plants/m2 yielded a stable GY range. Therefore, taking into account the persistence time for maximum LAI, the plant density required to obtain an ideal GY maize canopy structure should be increased by 10–18% from 9.72 plants/m2.