Efficacy and Safety of Low-Dose, Rapidly Infused Bamlanivimab and Etesevimab: Phase 3 BLAZE-1 Trial for Mild-to-Moderate COVID-19.

INTRODUCTION: The monoclonal antibody therapies bamlanivimab (BAM) + etesevimab (ETE) received emergency use authorization (EUA) from the US Food and Drug Administration (February 9, 2021) for treatment of mild-to-moderate COVID-19. The EUA of BAM + ETE was revoked (December 14, 2023) due to the high prevalence of BAM + ETE-resistant variants of SARS-CoV-2. Efficacy and safety of 700/1400 mg and 2800/2800 mg BAM + ETE are well established and published; however, efficacy and safety of 350/700 mg BAM + ETE have not been disclosed to date. METHODS: This portion of phase 3, BLAZE-1 trial (J2X-MC-PYAB) enrolled patients (between June 17, 2020 and April 9, 2021) with mild-to-moderate COVID-19 within 3 days of laboratory diagnosis of SARS-CoV-2 infection. In total, 354 patients with at least one risk factor for severe COVID-19 were enrolled, randomized (2:3), and infused with placebo (N = 141) or 350/700 mg BAM + ETE (N = 213), over ~ 8 min. Primary endpoint was to assess proportion of patients with persistently high SARS-CoV-2 viral load (PHVL) (log viral load > 5.27) 7 days after infusion. RESULTS: Patients were aged (mean) 53 years, 49.7% female, and 82.7% White. Seven days after drug infusion, 10.8% (95% confidence interval: 6.6, 15.0; p < 0.001) of BAM + ETE-treated patients and 34.8% (26.9, 42.6) of placebo-treated patients had PHVL, and the viral load change from baseline (least square mean [standard error]) was - 3.50 (0.15; p < 0.001) in BAM + ETE-treated patients versus - 2.51 (0.19) in placebo-treated patients. The majority of treatment-emergent adverse events were considered mild or moderate in severity (BAM + ETE: 6.6%; placebo: 14.2%). No deaths were reported. CONCLUSIONS: Consistent with previous studies, patients treated with BAM + ETE (350/700 mg) had a significantly lower proportion of PHVL and greater reduction in viral load compared with placebo. The overall safety profile is consistent with higher doses of BAM + ETE. Infusions of over ~ 8 min did not result in meaningful increase in incidence of TEAEs compared to higher doses of BAM + ETE administered over 30-60 min. TRIAL REGISTRATION: Clinical trial.gov identifier, NCT04427501.

[Success Factors for the Labour Market Integration of People with Psychosocial Disabilities - A Qualitative Survey in Austrian Companies]. / Gelingensfaktoren für die Arbeitsmarktintegration von Menschen mit psychischer Beeinträchtigung ­ eine qualitative Befragung von Betrieben in Österreich.

OBJECTIVE: The study examines conditions to promote employment and workplace integration of people with psychosocial disabilities. METHOD: 26 guided interviews were conducted with Austrian companies. 15 of these companies employed people with mental disabilities at the time of the interview. The remaining 11 companies did not employ anyone who had a declared mental illness. RESULTS: Companies that employ people with mental disabilities refer to an idealistic, social or socio-political motive for employment and have manifold supportive measures in place. Companies that do not employ people with mental disabilities express insecurities and ambivalent expectations regarding employment of people with mental disabilities. CONCLUSION: Results show that it is imperative to inform companies of the possibilities and conditions of workplace integration of people with psychosocial disabilities.

Ecotoxicity of Caffeine as a Bio-Protective Component of Flax-Fiber-Reinforced Epoxy-Composite Building Material.

Caffeine is a verified bio-protective substance in the fight against the biodegradation of cellulose materials, but its ecotoxicity in this context has not yet been studied. For this reason, the ecotoxicity of flax-fiber-reinforced epoxy composite with or without caffeine was tested in the present study. Prepared samples of the composite material were tested on freshwater green algal species (Hematococcus pluvialis), yeasts (Saccharomyces cerevisae), and crustacean species (Daphnia magna). Aqueous eluates were prepared from the studied material (with caffeine addition (12%) and without caffeine and pure flax fibers), which were subjected to chemical analysis for the residues of caffeine or metals. The results indicate the presence of caffeine up to 0.001 mg/L. The eluate of the studied material was fully toxic for daphnids and partially for algae and yeasts, but the presence of caffeine did not increase its toxicity statistically significantly, in all cases. The final negative biological effects were probably caused by the mix of heavy metal residues and organic substances based on epoxy resins released directly from the tested composite material.

Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial.

INTRODUCTION: Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. METHODS: In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. RESULTS: The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. CONCLUSION: WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. TRIAL REGISTRATION NUMBER: NCT04427501.

Long-term fungal inoculation of Ficus sycomorus and Tectona grandis woods with Aspergillus flavus and Penicillium chrysogenum.

In the current study, two molds, Aspergillus flavus (ACC# LC325160) and Penicillium chrysogenum (ACC# LC325162) were inoculated into two types of wood to be examined using scanning electron microscopy-energy dispersive X-ray (SEM-EDX) and computerized tomography (CT) scanning. Ficus sycomorus, a non-durable wood, and Tectona grandis, a durable wood, were the two wood blocks chosen, and they were inoculated with the two molds and incubated for 36 months at an ambient temperature of 27 ± 2 °C and 70 ± 5% relative humidity (RH). The surface and a 5-mm depth of inoculated wood blocks were histologically evaluated using SEM and CT images. The results showed that A. flavus and P. chrysogenum grew enormously on and inside of F. sycomorus wood blocks, but T. grandis wood displayed resistance to mold growth. The atomic percentages of C declined from 61.69% (control) to 59.33% in F. sycomorus wood samples inoculated with A. flavus while O increased from 37.81 to 39.59%. P. chrysogenum caused the C and O atomic percentages in F. sycomorus wood to drop to 58.43%, and 26.34%, respectively. C with atomic percentages in Teak wood's C content fell from 70.85 to 54.16%, and 40.89%, after being inoculated with A. flavus and P. chrysogenum. The O atomic percentage rose from 28.78 to 45.19% and 52.43%, when inoculated with A. flavus and P. chrysogenum, respectively. Depending on how durable each wood was, The examined fungi were able to attack the two distinct types of wood in various deterioration patterns. T. grandis wood overtaken by the two molds under study appears to be a useful material for a variety of uses.

Ecotoxicity and Biodegradation of Sustainable Environment-Friendly Bone-Glue-Based Adhesive Suitable for Insulation Materials.

Bone glue with sodium lignosulfonate is a protein-based adhesive. Their combination leads to strong binding necessary for the achievement of adhesive properties. However, biodegradation and ecotoxicity of materials composed of bone glue and sodium lignosulfonate has never been studied before. In this paper, the biodegradation potential of the mixture of bone glue, lignosulfonate and rape straw modified by water or NaOH on an agar test with aerial molds and in acute aquatic tests with mustard, yeasts, algae and crustaceans was analyzed. Epoxy resin as an ecologically unfriendly binder was used as a negative control and pure rape straw as a background. The results indicated that all samples were covered by molds, but the samples containing straw treated by NaOH showed lower biodegradability. The ecotoxicological effects varied among the applied model organisms. Artemia salina was not able to survive and S. alba could not prolong roots in the eluates of all samples (100% inhibition). Freshwater algae (D. subspicatus) were not significantly affected by the samples (max. 12% inhibition, max. 16% stimulation). The biomass of yeasts (S. cerevisae) was strongly stimulated in the presence of eluates in a comparison to control (max. 38% stimulation).

Environmental Consequences of Rubber Crumb Application: Soil and Water Pollution.

End-of-life tires are utilized for various purposes, including sports pitches and playground surfaces. However, several substances used at the manufacture of tires can be a source of concerns related to human health or environment's adverse effects. In this context, it is necessary to map whether this approach has the desired effect in a broader relation. While the negative effects on human health were investigated thoroughly and legislation is currently being revisited, the impact on aquatic or soil organisms has not been sufficiently studied. The present study deals with the exposure of freshwater and soil organisms to rubber crumb using the analysis of heavy metal and polycyclic aromatic hydrocarbon concentrations. The obtained results refer to substantial concerns related to freshwater contamination specifically, since the increased concentrations of zinc (7 mg·L-1) and polycyclic aromatic hydrocarbons (58 mg·kg-1) inhibit the growth of freshwater organisms, Desmodesmus subspicatus, and Lemna minor in particular. The performed test with soil organisms points to substantial concerns associated with the mortality of earthworms as well. The acquired knowledge can be perceived as a roadmap to a consistent approach in the implementation of the circular economy, which brings with it a number of so far insufficiently described problems.

Effects of Secondary Porosity on Microstructure and Mechanical Properties of SAP-Containing Lime-Based Plasters.

Despite the many benefits associated with the utilization of superabsorbent polymers (SAPs), several drawbacks have been reported. In particular, the effect of SAPs on microstructure, together with its consequences for mechanical properties, is not fully understood yet for some composite materials. This study analyzes the role of SAPs in the formation of the microstructure of lime composites, taking into account their chemical composition. The obtained experimental results show that the particle size and cross-linking density of used SAPs are crucial parameters affecting both the microstructure and mechanical performance of the analyzed composites. Coarser SAPs with low cross-linking density in the dosage of 0.5 and 1 wt.% are found as the most suitable solution, leading even to a slight improvement of mechanical parameters. The secondary porosity formed by swelled hydrogels is identified as a very significant factor since hydrogel-filled voids do not contribute to the strength parameters. The formation of the affected zone around SAP cores depends on the chemical composition of SAPs considerably as the higher cross-linking density influences the desorption rate. Based on achieved results, utilization of SAPs in building materials should be studied at a more detailed level with particular importance on the definition of SAP-related voids and affected zone around SAP particles.

[Motives for the use of psychosocial aftercare services]. / Motive für die Inanspruchnahme von psychosozialen Unterstützungsleistungen.

BACKGROUND: There are hardly any studies regarding the specific motives for the use of psychosocial aftercare services. The present study aims to fill this gap by investigating the motives for the use of certain psychosocial aftercare services for people with mental health problems. In particular, the services Ability-Oriented Activity, Mobile Care and Help, Psychosocial Counseling Center and Housing are considered. METHODS: Data from a client satisfaction surveys which had been conducted on an annual basis over a period of 5 years (2013-2017) were analyzed. Clients were surveyed regarding the importance of 5 motives for service use (getting support with problems; being able to talk to someone about problems; feeling understood; having a space of safety; feeling like they are doing something for their health) using a 5-point response scale. RESULTS AND CONCLUSIONS: The analyses of the data show that across all services, the motive "feeling understood" is of great importance for the use of psychosocial services. Apart from this motive, it is primarily safety that motivate the use of services of ability-oriented activity and housing. In the case of Mobile Care and Assistance and the Psychosocial Counseling Center, it is predominantly instrumental aspects, such as getting support with problems. In general, it can be seen that the motivational strength, i.e. how important these reasons are for using the service, is highest for the services provided by Mobile Care and Assistance and the Psychosocial Counseling Center.

X-ray computed tomography (CT) and ESEM-EDS investigations of unusual subfossilized juniper cones.

Recent investigations of a Greco-Roman site at Sais have provided well-preserved archaeobotanical remains within a pile of metal fragments. The remains are compared with comparable modern taxa. The morphology and anatomy are studied using Light microscope (LM), Environmental scanning electron microscope (ESEM) and X-ray computed tomography (CT). To investigate the preservation mode, Energy dispersive spectroscopy (EDS) analysis and elemental mapping are conducted. Results revealed that the archaeobotanical remains are exhibiting close affinity with modern juniper cones. Although, the studied archaeobotanical remains are buried for more than 2 millenniums, they underwent early stages of silicification and copper mineralization. These results are discussed in relation to other excavated objects in the find and to our knowledge and understanding of daily life in the Greco-Roman period.

The Effects of Iron Rust on the Ageing of Woods and Their Derived Pulp Paper.

The accelerated ageing of wood in terms of heating or iron rusting has a potential effect on the physio-mechanical, chemical and biological properties of wood. The effects of accelerated ageing on the mechanical, physical and fungal activity properties of some wood materials (Schinus terebinthifolius, Erythrina humeana, Tectona grandis, Pinus rigida and Juglans nigra) were studied after several cycles of heating and iron rusting. The fungal activity was assayed against the growth of Aspergillus terreus, Aspergillus niger, Fusarium culmorum and Stemphylium solani. In addition, the mechanical and optical properties of paper sheets produced from those wood pulps by means of Kraft cooking were evaluated. The mechanical and chemical properties of the studied wood species were affected significantly (p < 0.05) by the accelerated ageing, compared to control woods. With Fourier transform infrared (FTIR) spectroscopy, we detected an increase in the intensity of the spectra of the functional groups of cellulose in the heated samples, which indicates an increase in cellulose content and decrease in lignin content, compared to other chemical compounds. For pulp properties, woods treated by heating showed a decrease in the pulp yield. The highest significant values of tensile strength were observed in pulp paper produced from untreated, heated and iron-rusted P. rigida wood and they were 69.66, 65.66 and 68.33 N·m/g, respectively; we calculated the tear resistance from pulp paper of untreated P. rigida (8.68 mN·m2/g) and T. grandis (7.83 mN·m2/g) and rusted P. rigida (7.56 mN·m2/g) wood; we obtained the values of the burst strength of the pulp paper of untreated woods of P. rigida (8.19 kPa·m2/g) and T. grandis (7.49 kPa·m2/g), as well as the fold number of the pulp paper of untreated, heated and rusted woods from P. rigida, with values of 195.66, 186.33 and 185.66, respectively. After 14 days from the incubation, no fungal inhibition zones were observed. Accelerated ageing (heated or iron-rusted) produced significant effects on the mechanical and chemical properties of the studied wood species and affected the properties of the produced pulp paper.

Microstructure Formation of Cement Mortars Modified by Superabsorbent Polymers.

The utilization of superabsorbent polymers (SAPs) in cement-based materials has been found to be a promising means of mitigating the autogenous propagation of shrinkage and cracks. On the other hand, the undesired effects of SAPs' application on functional properties, including mechanical strength, microstructure formation, and the evolution of hydration heat are not properly understood, given the variety in SAPs' characteristics. To contribute to the present state-of-the-art, cement mortars, modified with two grades of SAPs by dosages of 0.3%, 0.6%, and 0.9%, were designed and studied with emphasis on the relationship between the materials' porosities and mechanical strengths. The obtained results are interpreted by scanning electron microscopy analysis and hydration heat evolution to elucidate the major changes and their driving factors. Besides the benefits associated with the mitigation of autogenous shrinkage, the achieved results point to an adverse effect of supplementation with SAP on mechanical strength at an early age, and an even more pronounced increase at a later age. The employed scanning electron microscopy images, together with mercury-intrusion porosimetry data, depict distortion in the material porosity as a result of the filling of formed voids and the closing of open ends by swelled hydrogels. Only the minor benefit of a greater cross-linking density was obtained by the formation of dense structures and the gains in mechanical strength therefrom.