Surgical interventions for degenerative lamellar macular holes

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effect of surgical interventions on postoperative visual and anatomical outcomes in people with a confirmed degenerative lamellar macular hole

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

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

Detection of flooded urban areas in high resolution Synthetic Aperture Radar images using double scattering

Flooding is a particular hazard in urban areas worldwide due to the increased risks to life and property in these regions. Synthetic Aperture Radar (SAR) sensors are often used to image flooding because of their all-weather day-night capability, and now possess sufficient resolution to image urban flooding. The flood extents extracted from the images may be used for flood relief management and improved urban flood inundation modelling. A difficulty with using SAR for urban flood detection is that, due to its side-looking nature, substantial areas of urban ground surface may not be visible to the SAR due to radar layover and shadow caused by buildings and taller vegetation. This paper investigates whether urban flooding can be detected in layover regions (where flooding may not normally be apparent) using double scattering between the (possibly flooded) ground surface and the walls of adjacent buildings. The method estimates double scattering strengths using a SAR image in conjunction with a high resolution LiDAR (Light Detection and Ranging) height map of the urban area. A SAR simulator is applied to the LiDAR data to generate maps of layover and shadow, and estimate the positions of double scattering curves in the SAR image. Observations of double scattering strengths were compared to the predictions from an electromagnetic scattering model, for both the case of a single image containing flooding, and a change detection case in which the flooded image was compared to an un-flooded image of the same area acquired with the same radar parameters. The method proved successful in detecting double scattering due to flooding in the single-image case, for which flooded double scattering curves were detected with 100% classification accuracy (albeit using a small sample set) and un-flooded curves with 91% classification accuracy. The same measures of success were achieved using change detection between flooded and un-flooded images. Depending on the particular flooding situation, the method could lead to improved detection of flooding in urban areas

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

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 µg sensitivity and a 3.5 min run time. The entire workflow was designed as an application to aggregation-prone mAbs and “mAb-like” 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 μg 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

Magnetic fields in cosmic particle acceleration sources

We review here some magnetic phenomena in astrophysical particle accelerators associated with collisionless shocks in supernova remnants, radio galaxies and clusters of galaxies. A specific feature is that the accelerated particles can play an important role in magnetic field evolution in the objects. We discuss a number of CR-driven, magnetic field amplification processes that are likely to operate when diffusive shock acceleration (DSA) becomes efficient and nonlinear. The turbulent magnetic fields produced by these processes determine the maximum energies of accelerated particles and result in specific features in the observed photon radiation of the sources. Equally important, magnetic field amplification by the CR currents and pressure anisotropies may affect the shocked gas temperatures and compression, both in the shock precursor and in the downstream flow, if the shock is an efficient CR accelerator. Strong fluctuations of the magnetic field on scales above the radiation formation length in the shock vicinity result in intermittent structures observable in synchrotron emission images. Resonant and non-resonant CR streaming instabilities in the shock precursor can generate mesoscale magnetic fields with scale-sizes comparable to supernova remnants and even superbubbles. This opens the possibility that magnetic fields in the earliest galaxies were produced by the first generation Population III supernova remnants and by clustered supernovae in star forming regions.Comment: 30 pages, Space Science Review

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

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 $\sim$ 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

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 ≥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 δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-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

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 ≥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 δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-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

Excited states in the N=88 nucleus Tb153 were observed up to spin ∼40 in an experiment utilizing the Gammasphere array. The Tb153 states were populated in a weak α4n evaporation channel of the Cl37 + Sn124 reaction. Two previously known sequences were extended to higher spins, and a new decoupled structure was identified. The πh11/2 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