A low-cost, low-crosstalk, and full-resolution autostereoscopic three-dimensional (3D) display system is described in this paper. The vivid 3D image is realized with the crosstalk below 10%. The full ...resolution of the display panel is retained by displaying left and right images sequentially and switching the light emitting diode (LED) directional backlight in synchronism with this. An eye position tracker is used to control the output of the LEDs with a liquid crystal spatial light modulator (SLM) so that the left and right exit pupils formed are located at the user's left and right eyes. The depth of this system is less than 20 cm and the cost are considerably lower than commercial 3D display systems, which makes it suitable for domestic desktop 3D display applications.
Introduction
Valoctocogene roxaparvovec uses an adeno‐associated virus serotype 5 (AAV5) vector to transfer a factor VIII (FVIII) coding sequence to individuals with severe haemophilia A, providing ...bleeding protection.
Aim
To assess safety and efficacy of valoctocogene roxaparvovec 5‒6 years post‐treatment.
Methods
In a phase 1/2 trial, adult male participants with severe haemophilia A (FVIII ≤1 IU/dL) without FVIII inhibitors or anti‐AAV5 antibodies received valoctocogene roxaparvovec and were followed for 6 (6 × 1013 vg/kg; n = 7) and 5 (4 × 1013 vg/kg; n = 6) years. Safety, including investigation of potential associations between a malignancy and gene therapy, and efficacy are reported.
Results
No new treatment‐related safety signals emerged. During year 6, a participant in the 6 × 1013 vg/kg cohort was diagnosed with grade 2 parotid gland acinar cell carcinoma; definitive treatment was uncomplicated parotidectomy with lymph node dissection. Target enrichment sequencing of tumour and adjacent healthy tissue revealed low vector integration (8.25 × 10−5 per diploid cell). Integrations were not elevated in tumour samples, no insertions appeared to drive tumorigenesis, and no clonal expansion of integration‐containing cells occurred. During all follow‐ups, >90% decreases from baseline in annualised treated bleeds and FVIII infusion rates were maintained. At the end of years 6 and 5, mean FVIII activity (chromogenic assay) was 9.8 IU/dL (median, 5.6 IU/dL) and 7.6 IU/dL (median, 7.1 IU/dL) for the 6 × 1013 and 4 × 1013 vg/kg cohorts, respectively, representing proportionally smaller year‐over‐year declines than earlier timepoints.
Conclusions
Valoctocogene roxaparvovec safety and efficacy profiles remain largely unchanged; genomic investigations showed no association with a parotid tumour.
This study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine Phe ammonia lyase PAL conjugated with polyethylene glycol PEG) treatment in adults with ...phenylketonuria (PKU) and its impact on safety and efficacy.
Immunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study. Pegvaliase-specific IgE levels were measured in patients after hypersensitivity adverse events (HAE).
All patients developed ADA against PAL, peaking by 6 months and then stabilizing. Most developed transient antibody responses against PEG, peaking by 3 months, then returning to baseline by 9 months. Binding of ADA to pegvaliase led to CIC formation and complement activation, which were highest during early treatment. Blood Phe decreased over time as CIC levels and complement activation declined and pegvaliase dosage increased. HAEs were most frequent during early treatment and declined over time. No patient with acute systemic hypersensitivity events tested positive for pegvaliase-specific IgE near the time of the event. Laboratory evidence was consistent with immune complex-mediated type III hypersensitivity. No evidence of pegvaliase-associated IC-mediated end organ damage was noted.
Despite a universal ADA response post-pegvaliase administration, adult patients with PKU achieved substantial and sustained blood Phe reductions with a manageable safety profile.
BioMarin Pharmaceutical Inc.
NiO/palygorskite composites had been fabricated by combining hydrothermal and calcining methods. The structure, morphology, surface area and pore distribution of the as-prepared NiO/palygorskite ...composites were characterized by the techniques such as powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectrum (EDS) and Brunauer-Emmett-Teller (BET). The synthesized NiO/palygorskite composite had larger BET surface area of 129.2 m2/g. The obtained NiO/palygorskite composites showed high specific capacitance of 1085.3 F/g at current density of 0.25 A/g.
To investigate the risk factors of cognitive impairment in post-intensive care syndrome patient (PICS-CI).
A retrospective study was conducted. The patient who transferred from post-intensive care ...unit (ICU) to the general ward for more than 7 days, and with the age ≥ 18 years old in the First Affiliated Hospital of Jinzhou Medical University from October 2015 to November 2016 were enrolled. The gender, age, marital status, education, occupation, salary, economic income, smoking, alcohol drinking, previous of history, mechanical ventilation, the length of ICU stay, sedative and delirium, and initial diagnosis were recorded. According to mini-mental state examination (MMSE), the patients were divided into cognitive impairment (CI) group and non-CI group. Univariate analysis was performed to identify the risk factors of PICS-CI, and variables with statistical difference were selected to do multivariate binary logistic regression analysis for the confirmable independence risk factors.
104 of the 290 patients developed CI, and the incidence was 35.86%. Univariate analysis showed that the gender, age, education, financial situation, smoking, alcohol drinking, previous of history, mechanical ventilation, the length of ICU stay, sedative and delirium, and initial diagnosis were recorded of ICU were main predictors of PICS-CI patients. It was shown by multivariate binary logistic regression analysis that the age > 60 years old odds ratio (OR) = 7.523, 95% confidence interval (95%CI) = 2.572-37.851, P = 0.001, mechanical ventilation (OR = 8.773, 95%CI = 2.588-36.344, P < 0.001), sedation (OR = 9.376, 95%CI = 2.661-42.011, P = 0.002), and delirium (OR = 13.201, 95%CI = 2.502-41.433, P < 0.001) were PICS-CI independence risk factors.
Nurse staffs should strength care and attention on ICU transferred out patients. In order to minimize PICS impairment, special precaution should be implemented according to different aspects.
The sediment discharge from the Yangtze River Basin has a stepwise decreasing trend in recent years. The impounding of the Three Gorges Reservoir exacerbated this de- creasing trend and affected the ...change of the suspended sediment concentration （SSC） in the Yangtze River Estuary through the transmission effect. The SSC data of the Yangtze River Estuary during 1959-2012 showed that： （1） The SSC in the South Branch of the Yang- tze River in the estuary and in the off-shore sea area displayed decreasing trends and de- creased less towards the sea. At the same time, the difference in decreasing magnitude be- tween SSC and sediment discharge became bigger towards the sea. （2） For the North Branch the preferential flow did not change much but the SSC tended to decrease, which was mainly caused by the decrease of SSC in the South Branch and China East Sea. （3） Due to the de- creased runoff and the relatively strengthened tide, the peak area of the SSC in the bar shoal section in 2003-2012 moved inward for about 1/6 longitude unit compared with that in 1984-2002, and the inward-moving distance was in the order of flood season 〉 annual average 〉 dry season. （4） In the inlet of the South Passage, the SSC decreased mainly because the increase caused by resuspension and shore-groove exchange was less than the decrease caused by the sharp SSC decrease in the basin and the sea areas. The reverse was true in the middle section, where the SSC showed an increasing trend. （5） In the inlet of the North Passage, under the combined influence of decreased flow split and sediment split ratios, the decreased SSC in the basin and the sea area and decreased amount of resuspension, the SSC displayed a decreasing trend. In the middle section, because the increased amount caused by sediment going over the dyke was markedly more than the decreased amount caused by external environments, the SSC tended to increase. Holistically, the sharp decrease in sediment discharge caused synchronized SSC decreases in the Yangtze River Estuary. But there were still areas, where the SSC displayed increasing trends, indicatingsynchronicity and difference in the response of SSC to the sharp decrease in sediment discharge from the basin.
Inorganic/organic nanohybrids composed of arrayed TiO_2 nanotubes（Ti NTs）/porphyrin nanoparticles（NPs） have been fabricated via a wet chemical approach. The inorganic component, particularly the ...arrayed one-dimensional（1D） nanostructures, provides high charge-carrier mobility and rapid charge transport. The organic component exhibits extensive visible light absorption and good solution processability. Additionally, the geometric restraint by supramolecular assembly renders an improved photostability. A combination of these two components could thus allow for an efficient solar energy conversion. In this work, a colloid of porphyrin NPs prepared by a solvent exchange method is coated on anodic Ti NTs by means of a dip-coating treatment to form inorganic/organic hybrids. The hybrids exhibit an improvement on solar absorption and a significant enhancement on photocurrent generation at a small bias compared with individual component. Herein, the inorganic/organic nanohybrids are proved to be excellent photoanodes highly responsive to visible light and thus pave a way to discover new inorganic/organic assemblies for high-performance optoelectronic applications, as well as for device integration.
River basin reservoir construction affects water and sediment transport processes in downstream reaches. The downstream impact of the Three Gorges Projects （TGP） has started to become apparent： （1） ...reduction in flood duration and discharge, and significant reduction in sediment load. Although there was some restoration in downstream sediment load, the total amount did not exceed the pre-impoundment annual average; （2） in 2003-2014 the d 〉 0.125 mm （coarse sand） load was restored to some degree, and to a maximum at Jianli Station, which was mainly at the pre-impoundment average. After restoration, erosion and deposition characteristics of the sediment was identical to that before impoundment. The degree of restoration during 2008-2014 was less than during 2003-2007; （3） after TGP im- poundment, there was some restoration in d 〈 0.125 mm （fine sand） sediment load, however, it was {ower than the pre-impoundment average; （4） due to riverbed compensation, the d 〉 0.125 mm sediment load recovered to a certain degree after impoundment, however, the total did not exceed 4400x104 t/y. This was mainly limited by flood duration and the average flow rate, and was less affected by upstream main stream, tributaries, or lakes. Restoration of d 〈 0.125 mm suspended sediment was largely controlled by upstream main stream, tributaries, and lakes, as well as by riverbed compensation. Due to bed armoring, riverbed fine suspended sediment compensation capability was weakened; （5） during 2003-2007 and 2008-2014, Yichang to Zhicheng and upper Jingjiang experienced coarse and fine erosion,lower Jingjiang experienced coarse deposition and fine erosion, Hankou to Datong had coarse deposition and fine erosion, and Chenglingji and Hankou was characterized by coarse deposition and fine sand erosion in 2003-2007, and coarse and fine erosion in 2008-2014. This difference was controlled by flood duration and number at Luoshan Station.
Background: This study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine Phe ammonia lyase PAL conjugated with polyethylene glycol PEG) treatment in adults with ...phenylketonuria (PKU) and its impact on safety and efficacy. Methods: Immunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study. Pegvaliase-specific IgE levels were measured in patients after hypersensitivity adverse events (HAE). Findings: All patients developed ADA against PAL, peaking by 6 months and then stabilizing. Most developed transient antibody responses against PEG, peaking by 3 months, then returning to baseline by 9 months. Binding of ADA to pegvaliase led to CIC formation and complement activation, which were highest during early treatment. Blood Phe decreased over time as CIC levels and complement activation declined and pegvaliase dosage increased. HAEs were most frequent during early treatment and declined over time. No patient with acute systemic hypersensitivity events tested positive for pegvaliase-specific IgE near the time of the event. Laboratory evidence was consistent with immune complex-mediated type III hypersensitivity. No evidence of pegvaliase-associated IC-mediated end organ damage was noted. Interpretation: Despite a universal ADA response post-pegvaliase administration, adult patients with PKU achieved substantial and sustained blood Phe reductions with a manageable safety profile. Fund: BioMarin Pharmaceutical Inc. Keywords: Enzyme replacement therapy, Antidrug antibody, Circulating immune complex, Hypersensitivity, Phenylalanine
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