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ObjectiveAmong individuals with chronic hepatitis B, those with hepatitis B e-antigen (HBeAg)-negative chronic hepatitis (CHB) can be difficult to distinguish from those with HBeAg-negative chronic HBV infection, also referred to as inactive HBV carriers (ICs), but both require different medical management. The level of HBV surface antigen (HBsAg) has been proposed as a marker to discriminate between chronic infection and hepatitis stages. HBsAg consists of large, middle and small HBs. The aim of this study was to determine whether the composition of HBsAg improved the identification of ICs among HBsAg-positive subjects with different phases of HBV infections.DesignHBV large surface proteins (LHBs) and HBV middle surface proteins (MHBs) were quantified in serum samples from 183 clinically well-characterised untreated patients with acute (n=14) HBV infection, ICs (n=44), CHBs (n=46), chronic HBeAg-positive phase (n=68) and hepatitis delta coinfection (n=11) using an ELISA, with well-defined monoclonal antibodies against the preS1 domain (LHBs) and the preS2-domain (MHBs). A Western blot analysis was used to verify the quantitation of the components of HBsAg. Total HBsAg was quantified using a modified commercially available assay (HBsAg V.6.0, Enzygnost, Siemens, Erlangen).ResultsThe composition of HBsAg showed specific patterns across different phases of hepatitis B. Individuals in the IC phase had significantly lower proportions of LHBs and MHBs than patients in acute or chronic phases irrespective of their HBV e-antigen status (p<0.0001) or HBsAg level. Both LHBs and MHBs ratios better predicted the IC phase than total HBsAg levels.ConclusionQuantification of MHBs, particularly LHBs represents a novel tool for the identification of the IC stage.

A galaxy at redshift z ≈ 8.6 Until now, the most distant spectroscopically confirmed galaxies known in the Universe were at redshifts z ≈ 8.2 and z ≈ 6.96. Lehnert et al . now report that UDFy-38135539 is at a redshift of z = 8.6. The galaxy was first identified as a candidate z ≈ 8.6 object in deep Wide Field Camera 3 observations of the Hubble Ultra Deep Field, and the discovery in ground-based observations that it is emitting Lyman-α photons provides confirmation. This single source is unlikely to provide enough photons to ionize the volume necessary for the emission line to escape, requiring a significant contribution from other, probably fainter galaxies nearby. Until now, the most distant spectroscopically confirmed galaxies known in the Universe were at redshifts of z = 8.2 and z = 6.96. It is now reported that the galaxy UDFy-38135539 is at a redshift of z = 8.5549 ± 0.0002. The finding has implications for our understanding of the timing, location and nature of the sources responsible for reionization of the Universe after the Big Bang. Galaxies had their most significant impact on the Universe when they assembled their first generations of stars. Energetic photons emitted by young, massive stars in primeval galaxies ionized the intergalactic medium surrounding their host galaxies, cleared sightlines along which the light of the young galaxies could escape, and fundamentally altered the physical state of the intergalactic gas in the Universe continuously until the present day 1 , 2 . Observations of the cosmic microwave background 3 , and of galaxies and quasars at the highest redshifts 4 , suggest that the Universe was reionized through a complex process that was completed about a billion years after the Big Bang, by redshift z  ≈ 6. Detecting ionizing Lyman-α photons from increasingly distant galaxies places important constraints on the timing, location and nature of the sources responsible for reionization. Here we report the detection of Lyα photons emitted less than 600 million years after the Big Bang. UDFy-38135539 (ref. 5 ) is at a redshift of z = 8.5549 ± 0.0002, which is greater than those of the previously known most distant objects, at z = 8.2 (refs 6 and 7 ) and z = 6.96 (ref. 8 ). We find that this single source is unlikely to provide enough photons to ionize the volume necessary for the emission line to escape, requiring a significant contribution from other, probably fainter galaxies nearby 9 .

Background Specialized evidence-based treatments have been developed and evaluated for borderline personality disorder (BPD), including Dialectical Behavior Therapy (DBT) and Schema Therapy (ST). Individual differences in treatment response to both ST and DBT have been observed across studies, but the factors driving these differences are largely unknown. Understanding which treatment works best for whom and why remain central issues in psychotherapy research. The aim of the present study is to improve treatment response of DBT and ST for BPD patients by a) identifying patient characteristics that predict (differential) treatment response (i.e., treatment selection) and b) understanding how both treatments lead to change (i.e., mechanisms of change). Moreover, the clinical effectiveness and cost-effectiveness of DBT and ST will be evaluated. Methods The BOOTS trial is a multicenter randomized clinical trial conducted in a routine clinical setting in several outpatient clinics in the Netherlands. We aim to recruit 200 participants, to be randomized to DBT or ST. Patients receive a combined program of individual and group sessions for a maximum duration of 25 months. Data are collected at baseline until three-year follow-up. Candidate predictors of (differential) treatment response have been selected based on the literature, a patient representative of the Borderline Foundation of the Netherlands, and semi-structured interviews among 18 expert clinicians. In addition, BPD-treatment-specific (ST: beliefs and schema modes; DBT: emotion regulation and skills use), BPD-treatment-generic (therapeutic environment characterized by genuineness, safety, and equality), and non-specific (attachment and therapeutic alliance) mechanisms of change are assessed. The primary outcome measure is change in BPD manifestations. Secondary outcome measures include functioning, additional self-reported symptoms, and well-being. Discussion The current study contributes to the optimization of treatments for BPD patients by extending our knowledge on “Which treatment – DBT or ST – works the best for which BPD patient, and why?”, which is likely to yield important benefits for both BPD patients (e.g., prevention of overtreatment and potential harm of treatments) and society (e.g., increased economic productivity of patients and efficient use of treatments). Trial registration Netherlands Trial Register, NL7699 , registered 25/04/2019 - retrospectively registered.

This study determined the gluten content of foods and meals consumed by coeliac disease (CD) patients who adhere to a gluten-free diet, and to estimate the total daily intake of gluten of these patients. CD patients fulfilling defined inclusion criteria were preselected and approached for participation in the study. Duplicate portions (DP) of foods and mixed dishes were collected from the CD patients for evaluating complete daily food intake during two individual days. Also, for these days, written food records were completed by the participants. From each DP, a laboratory sample was prepared and analysed for its gluten concentration and total daily gluten intake was calculated. Each individual’s total daily intakes of energy and macronutrients were calculated using the Dutch food composition database. In total, twenty-seven CD patients participated, seven males and twenty females, aged between 21 and 64 years. In thirty-two (6 %) of 499 food samples collected in total, more than 3 mg/kg gluten was present. In four of these thirty-two samples, the gluten concentration was above the European legal limit of 20 mg/kg and three of the four samples had a gluten-free label. The maximal gluten intake was 3·3 mg gluten/d. The gluten tolerance for sensitive CD patients (>0·75 mg/d) was exceeded on at least six out of fifty-four study days. To also protect these sensitive CD patients, legal thresholds should be re-evaluated and the detection limit of analytical methods for gluten analysis lowered.

We describe the production and characterization of human monoclonal antibodies (mAb) specific for the major hepatitis B virus (HBV) S protein. The mAbs, two IgG1κ and one IgG1λ, were secreted by B-cell clones obtained from peripheral blood mononuclear cells (PBMC) of one person convalescent from acute hepatitis B and one vaccinated individual. The former recognized a denaturation-insensitive epitope within the p24 protein whereas the latter recognized a denaturation-sensitive, conformational epitope located within the HBsAg common \"a\" determinant. This mAb, denominated ADRI-2F3, displayed a very high protective titer of over 43,000 IU/mg mAb and showed an extremely potent neutralizing activity in the in vitro model of HBV infection using primary hepatocytes from Tupaia belangeri as target. Recombinant variable heavy and light domain sequences derived from mAb ADRI-2F3 were cloned into eukaryotic expression vectors and showed identical fine specificity and 1 log10 higher titer than the original IgG1λ. It is envisaged that such mAb will be able to efficiently prevent HBV reinfection after liver transplantation for end-stage chronic HBV infection or infection after needle-stick exposure, providing an unlimited source of valuable protective anti-HBs antibody.

Unmanned aerial vehicle laser scanning (ULS) has recently become available for operational mapping and monitoring (e.g. for forestry applications or erosion studies). It combines advantages of terrestrial and airborne laser scanning, but there is still little proof of ULS accuracy. For the detection and monitoring of small-magnitude surfaces changes with multitemporal point clouds, an estimate of the level of detection (LOD) is required. The LOD is a threshold applied on distance measurements to separate real surface change (e.g. due to erosion or deposition by geomorphic processes) from errors. This paper investigates key components of the error budget for two ULS point clouds acquired for erosion monitoring at a grassland site in the Alps. In addition to the registration error and effects of the local surface roughness, we assess the positional uncertainties of each point that result from laser footprint effects, which are a function of the scanning geometry (including range, incidence angle and beam divergence). By removing erroneous points with an increasingly stricter point error criterion, we illustrate that the positional point errors strongly affect the LOD and discuss how this type of error can be mitigated. Moreover, our experimental results with three different surface classes (bare earth and rock, buildings and grassland) show that the level of detection tends to be slightly better for areas with bare earth and rock than for grass-covered areas (due to their roughness). For all these surface types reliable distance measurements are possible with sub-decimetre levels of detection.

With this contribution we assess the potential of unmanned aerial vehicle (UAV) based laser scanning for monitoring shallow erosion in Alpine grassland. A 3D point cloud has been acquired by unmanned aerial vehicle laser scanning (ULS) at a test site in the subalpine/alpine elevation zone of the Dolomites (South Tyrol, Italy). To assess its accuracy, this point cloud is compared with (i) differential global navigation satellite system (GNSS) reference measurements and (ii) a terrestrial laser scanning (TLS) point cloud. The ULS point cloud and an airborne laser scanning (ALS) point cloud are rasterized into digital surface models (DSMs) and, as a proof-of-concept for erosion quantification, we calculate the elevation difference between the ULS DSM from 2018 and the ALS DSM from 2010. For contiguous spatial objects of elevation change, the volumetric difference is calculated and a land cover class (bare earth, grassland, trees), derived from the ULS reflectance and RGB colour, is assigned to each change object. In this test, the accuracy and density of the ALS point cloud is mainly limiting the detection of geomorphological changes. Nevertheless, the plausibility of the results is confirmed by geomorphological interpretation and documentation in the field. A total eroded volume of 672 m3 is estimated for the test site (48 ha). Such volumetric estimates of erosion over multiple years are a key information for improving sustainable soil management. Based on this proof-of-concept and the accuracy analysis, we conclude that repeated ULS campaigns are a well-suited tool for erosion monitoring in Alpine grassland.

Point clouds derived from UAV-borne laser scanning and UAV-borne photogrammetry provide new opportunities for 3D topographic monitoring in geographic research. The airborne acquisition strategy overcomes common challenges of ground-based techniques, such as limited spatial coverage or heterogeneous measurement distribution, and allows flexible repeated acquisitions at high temporal and spatial resolution. While UAV-borne 3D sensing techniques are expected to thereby enhance geographic monitoring, their specific potential for methods and algorithms of 3D change analysis is yet to be investigated. In our study, we assess point clouds originating from UAV-borne photogrammetry using dense image matching (DIM) and UAV-borne laser scanning (ULS) as input for 3D topographic change analysis at an active rock glacier in the Austrian Alps. We analyse surface change by using ULS and DIM point clouds of 2019 and 2021 as input for two state-of-the-art methods for pairwise surface change analysis: (1) The Multiscale Model to Model Cloud Comparison (M3C2) algorithm and (2) a recent M3C2-based approach (CD-PB M3C2) using plane correspondences to reduce the uncertainty of quantified change. We evaluate ULS-based and DIM-based change analysis regarding their performance in (1) achieving high spatial coverage of derived changes, (2) accurately quantifying magnitudes and uncertainty of change, and (3) detecting significant change (change magnitudes > associated uncertainty). As reference we use change quantified between two terrestrial laser scanning (TLS) surveys undertaken simultaneously with the ULS and DIM data acquisitions. Our study shows the improved spatial coverage of M3C2 achieved with point clouds acquired with UAVs (+ 60% of core points used for change analysis). For CD-PB M3C2, ULS and DIM point clouds enabled a spatially more uniform distribution of plane pairs used for change quantification and a slightly higher spatial coverage (+6% – +7% of core points used for change analysis) compared to the TLS reference. Magnitudes of M3C2 change were closer to the TLS reference for ULS-ULS (mean difference: 0.04 m; std. dev.: 0.05 m) compared to ULS-DIM (mean difference: 0.12 m; std. dev.: 0.08 m). Similar results were obtained for CD-PB M3C2 using ULS-ULS (mean difference: 0.02 m; std. dev.: 0.01 m) and ULS-DIM (mean difference: 0.06 m; std. dev.: 0.01 m). Moreover, magnitudes of change were above the associated uncertainty in 82% – 89% (M3C2) and 89% – 90% (CD-PB M3C2) of the area of change analysis. Our findings demonstrate the potential of ULS and DIM point clouds as input for accurate 3D topographic change analysis for the study at hand and can support the design and setup of 3D/4D Earth observation systems for rock glaciers and natural scenes with complex topography, such as landslides or debris covered glaciers.

PurposeThe importance of follow-up (FU) for midterm weight loss (WL) after bariatric surgery is controversial. Compliance to this FU remains challenging. Several risk factors for loss to FU (LtFU) have been mentioned. The aim was therefore to evaluate the association between WL and LtFU 3 to 5 years postoperatively and to identify risk factors for LtFU.Materials and MethodsA single-center cross-sectional study in the Netherlands. Between June and October 2018, patients scheduled for a 3-, 4-, or 5-year FU appointment were included into two groups: compliant (to their scheduled appointment and overall maximally 1 missed appointment) and non-compliant (missed the scheduled appointment and at least 1 overall). Baseline, surgical, and FU characteristics were collected and a questionnaire concerning socio-economic factors.ResultsIn total, 217 patients in the compliant group and 181 in the non-compliant group were included with a median body mass index at baseline of 42.0 and 42.9 respectively. Eighty-eight percent underwent a laparoscopic Roux-en-Y gastric bypass. The median percentage total weight loss for the compliant and non-compliant groups was 30.7% versus 28.9% at 3, 29.3% versus 30.2% at 4, and 29.6% versus 29.9% at 5 years respectively, all p>0.05. Age, persistent comorbidities and vitamin deficiencies, a yearly salary <20,000 euro, no health insurance coverage, and not understanding the importance of FU were risk factors for LtFU.ConclusionThree to 5 years postoperatively, there is no association between LtFU and WL. The compliant group demonstrated more comorbidities and vitamin deficiencies. Younger age, not understanding the importance of FU, and financial challenges were risk factors for LtFU.

New geospatial technologies and ubiquitous sensing allow new insights into people’s spatial practices and experiences of public spaces. These tools offer new data streams for analysis and interpretation of social phenomena. Mobile augmented reality tools such as smartphones and wearables merge the experience of entangled online and offline spaces in citizen’s daily life. This paper demonstrates a concept that combines eye-tracking tools with innovative mapping in order to enhance the interpretability of real outdoor environmental experiences. Through videogrammetry, a participants’ head posture can be reconstructed. Subsequently the fixations measured through eye-tracking are projected onto a 3D point cloud of the surrounding environment. The presented methodological approach is implemented in the interdisciplinary project DigitAS – The Digital, Affects and Space – which investigates the perception of public places as spaces of recreation, security or fear. The project’s Mixed Methods approach combined qualitative, mobile, in-situ and reconstructive methods with eye-tracking in an outdoor setting. Potentials of the geospatial mapping concept for social science research is discussed.