253 research outputs found

    Foveal sparing internal limiting membrane peeling for idiopathic macular hole; effects on anatomical restoration of the fovea and visual function

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    Purpose: Muller cells appear to be important in maintaining foveal morphology through connections between their foot processes and the Internal limiting membrane (ILM). ILM peeling causes Muller cell trauma. We hypothesised that leaving a rim of unpeeled ILM around idiopathic macular holes (MH) undergoing vitrectomy surgery would improve postoperative foveal morphology and vision. Methods: Prospective pilot study of fovea-sparing ILM peeling in a consecutive cohort of patients with MHs over a 12-month period. SD-OCT and ETDRS letters visual acuity (BCVA) were assessed pre- and postoperatively, and foveal morphology and metamorphopsia postoperatively. The foveal sparing group (FSG) were compared to a second consecutive cohort who received standard ILM peeling (Control group, CG). Results: 34 eyes of 34 patients were included in each group. Groups showed no significant preoperative differences. 34/34 holes were successfully closed with surgery in FSG and 32/34 in CG. FSG showed better postoperative BCVA (67.7 versus 63.8, p=0.003) and BCVA improvement (25.1 versus 20.2, p=0.03). FSG demonstrated thicker minimum foveal thickness (211 versus 173 microns, p=0.002) and less steep foveal depression (158 versus 149, p=0.002). Conclusion: Preserving non-peeled ILM around MHs resulted in a high closure rate, improved foveal morphology and better postoperative BCVA. An appropriately powered randomised controlled study is warranted

    An automated, low volume, and high-throughput analytical platform for aggregate quantitation from cell culture media

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    High throughput screening methods have driven a paradigm shift in biopharmaceutical development by reducing the costs of good manufactured (COGM) and accelerate the launch to market of novel drug products. Scale-down cell culture systems such as shaken 24- and 96-deep-well plates (DWPs) are used for initial screening of hundreds of recombinant mammalian clonal cell lines to quickly and efficiently select the best producing strains expressing product quality attributes that fit to industry platform. A common modification monitored from early-stage product development is protein aggregation due to its impact on safety and efficacy. This study aims to integrate high-throughput analysis of aggregation-prone therapeutic proteins with 96-deep well plate screening to rank clones based on the aggregation levels of the expressed proteins. Here we present an automated, small-scale analytical platform workflow combining the purification and subsequent aggregation analysis of protein biopharmaceuticals expressed in 96-DWP cell cultures. Product purification was achieved by small-scale solid-phase extraction using dual flow chromatography (DFC) automated on a robotic liquid handler for the parallel processing of up to 96 samples at a time. At-line coupling of size-exclusion chromatography (SEC) using a 2.1 mm ID column enabled the detection of aggregates with sub-2 Āµg sensitivity and a 3.5 min run time. The entire workflow was designed as an application to aggregation-prone mAbs and ā€œmAb-likeā€ next generation biopharmaceuticals, such as bispecific antibodies (BsAbs). Application of the high-throughput analytical workflow to a shake plate overgrow (SPOG) screen, enabled the screening of 384 different clonal cell lines in 32 h, requiring < 2 Ī¼g of protein per sample. Aggregation levels expressed by the clones varied between 9 and 76%. This high-throughput analytical workflow allowed for the early elimination of clonal cell lines with high aggregation, demonstrating the advantage of integrating analytical testing for critical quality attributes (CQAs) earlier in product development to drive better decision making

    Correlations between the peak flux density and the position angle of inner-jet in three blazars

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    We aim to investigate the relation between the long-term flux density and the position angle (PA) evolution of inner-jet in blazars. We have carried out the elliptic Gaussian model-fit to the `core' of 50 blazars from 15 GHz VLBA data, and analyzed the variability properties of three blazars from the model-fit results. Diverse correlations between the long-term peak flux density and the PA evolution of the major axis of the `core' have been found in āˆ¼\sim 20% of the 50 sources. Of them, three typical blazars have been analyzed, which also show quasi-periodic flux variations of a few years (T). The correlation between the peak flux density and the PA of inner-jet is positive for S5~0716+714, and negative for S4~1807+698. The two sources cannot be explained with the ballistic jet models, the non-ballistic models have been analyzed to explain the two sub-luminal blazars. A correlation between the peak flux density and the PA (with a T/4 time lag) of inner-jet is found in [HB89]~1823+568, this correlation can be explained with a ballistic precession jet model. All the explanations are based mainly on the geometric beaming effect; physical flux density variations from the jet base would be considered for more complicated situations in future, which could account for the no or less significance of the correlation between the peak flux density and the PA of inner-jet in the majority blazars of our sample.Comment: 6 pages, 7 figures, accepted for publication in Astrophysics and Space Scienc

    EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks

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    BACKGROUND AND AIMS: Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. APPROACH AND RESULTS: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ā‰„3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic Ī“-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, Ī“-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. (Hepatology 2020;71:1546-1558)

    EXPLORE: A prospective, multinational natural history study of patients with acute hepatic porphyria with recurrent attacks

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    BACKGROUND AND AIMS: Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. APPROACH AND RESULTS: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ā‰„3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic Ī“-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, Ī“-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. (Hepatology 2020;71:1546-1558)

    Persistence of collective behavior at high spin in the N=88 nucleus Tb 153

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    Excited states in the N=88 nucleus Tb153 were observed up to spin āˆ¼40 in an experiment utilizing the Gammasphere array. The Tb153 states were populated in a weak Ī±4n evaporation channel of the Cl37 + Sn124 reaction. Two previously known sequences were extended to higher spins, and a new decoupled structure was identified. The Ļ€h11/2 band was observed in the spin region where other N=88 isotopes exhibit effects of prolate to oblate shape changes leading to band termination along the yrast line, whereas Tb153 displays a persistent collective behavior. However, minor perturbations of the very highest state in both signatures of this h11/2 band are observed, which perhaps signal the start of the transition towards band termination

    Collective structures up to spin āˆ¼ 65h in the N 90 isotones 158Er and 157Ho

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    A new collective band with high dynamic moment of inertia in 158Er at spins beyond band termination has been found in addition to the two previously reported ones. The measured transition quadrupole moments (Qt) of these three bands are very similar. These three bands have been suggested to possess a triaxial strongly deformed shape, based on comparisons with calculations using the cranked Nilsson-Strutinsky model and with tilted axis cranking calculations using the Skyrme-Hartree-Fock model. In addition, three collective bands with similar high dynamic moments of inertia, tentatively assigned to 157Ho, have been observed. Thus, it is suggested that all these structures share a common underlying character and that they are most likely associated with triaxial strongly deformed minima which are predicted to be close to the yrast line at spin 50 - 70h
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