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Summary: Urban air undergoes transformations as it is actively circulated throughout buildings via ventilation systems. However, the influence of air exchange between outdoor and indoor atmospheres on urban air pollution is not well understood. Here, we quantify how buildings behave as a dynamic source and sink for urban air pollutants via high-resolution online mass spectrometry measurements. During our field campaign in a high-performance office building, we observed that the building continually released volatile organic compounds (VOCs) into the urban air and removed outdoor ozone and fine particulate matter. VOC emissions from people, their activities, and surface reservoirs result in significant VOC discharge from the building to the outdoors. Per unit area, building emissions of VOCs are comparable to traffic, industrial, and biogenic emissions. The building source-sink behavior changed dynamically with occupancy and ventilation conditions. Our results demonstrate that buildings can directly influence urban air quality due to substantial outdoor-indoor air exchange. Science for society: Buildings account for a significant fraction of the land area in cities and actively exchange air with their proximate outdoor environments via mechanical ventilation systems. However, the direct impact of buildings on urban air pollution remains poorly characterized. Due to reductions in traffic-associated emissions of volatile organic compounds (VOCs), volatile chemical products, which are widely used inside buildings, have become a major VOC source in urban areas. Indoor-generated VOCs are likely to be an important contributor to the VOC burden of the urban atmosphere, and ventilation systems provide a pathway for VOCs to be released outdoors. Here, we show how modern buildings act as significant emission sources of VOCs for the outdoor environment. Our results demonstrate that future air quality monitoring efforts in cities need to account for direct VOC discharge from buildings in order to capture emerging sources of environmental pollution that can impact the climate and human health.

Abstract Background Parameters of body composition have prognostic potential in patients with oncologic diseases. The aim of the present study was to analyse the prognostic potential of radiomics‐based parameters of the skeletal musculature and adipose tissues in patients with advanced hepatocellular carcinoma (HCC). Methods Radiomics features were extracted from a cohort of 297 HCC patients as post hoc sub‐study of the SORAMIC randomized controlled trial. Patients were treated with selective internal radiation therapy (SIRT) in combination with sorafenib or with sorafenib alone yielding two groups: (1) sorafenib monotherapy (n = 147) and (2) sorafenib and SIRT (n = 150). The main outcome was 1‐year survival. Segmentation of muscle tissue and adipose tissue was used to retrieve 881 features. Correlation analysis and feature cleansing yielded 292 features for each patient group and each tissue type. We combined 9 feature selection methods with 10 feature set compositions to build 90 feature sets. We used 11 classifiers to build 990 models. We subdivided the patient groups into a train and validation cohort and a test cohort, that is, one third of the patient groups. Results We used the train and validation set to identify the best feature selection and classification model and applied it to the test set for each patient group. Classification yields for patients who underwent sorafenib monotherapy an accuracy of 75.51% and area under the curve (AUC) of 0.7576 (95% confidence interval [CI]: 0.6376–0.8776). For patients who underwent treatment with SIRT and sorafenib, results are accuracy = 78.00% and AUC = 0.8032 (95% CI: 0.6930–0.9134). Conclusions Parameters of radiomics‐based analysis of the skeletal musculature and adipose tissue predict 1‐year survival in patients with advanced HCC. The prognostic value of radiomics‐based parameters was higher in patients who were treated with SIRT and sorafenib.

Richard Radnovich,1 Jill Heinz,1 Chris Ambrose,2 Elizabeth Stannard,2 Dmitri Lissin2 1Injury Care Research, Boise, ID, USA; 2Global Research and Development, Scilex Pharmaceuticals Inc, Palo Alto, CA, USACorrespondence: Dmitri LissinScilex Pharmaceuticals Inc, 960 San Antonio Road, Palo Alto, CA, 94306, USA, Tel +1 650-430-3238Email dlissin@scilexpharma.comPurpose: SP-102 is a novel epidural steroid injection (ESI) formulation of 10 mg dexamethasone sodium phosphate in a viscous gel solution. Repeat dosing of ESIs is possible if required for pain relief, but with consideration of hypothalamic–pituitary–adrenal (HPA) axis suppression from prolonged systemic exposure. This phase I/II study investigated the effect of initial and repeat SP-102 injections on HPA suppression and analgesia.Methods: Subjects with lumbosacral radiculopathy received an initial epidural SP-102 injection (T1) on day 1, followed by a repeat injection (T2) on ≥ 28 days later. To determine HPA suppression, area under the effect curve over 28 days and maximum change from baseline were calculated for cortisol, glucose levels, and white blood cell (WBC) count. Equivalent effect on HPA suppression of T1 relative to T2 was determined if the 90% CIs for ratios of these measures were within 80%– 125%. The effect of repeat injections on leg and back pain was also assessed.Results: Based on the responder analysis, all subjects had achieved a cortisol response by day 3 after initial injection and by day 2 after repeat injection. The repeat injection had similar effects on glucose levels and WBC count to the initial injection. Pain scores decreased after each injection and remained low for the 28-day follow-up, with some evidence of improved analgesic effect of the second dose compared with the first. There were no serious adverse events or discontinuations due to adverse events.Conclusion: The lack of cumulative effect and rapid resolution of HPA suppression following repeated SP-102 dosing suggests that consideration of HPA pharmacodynamics is not clinically relevant when making decisions regarding repeat dosing. SP-102 ESIs provided prolonged pain relief, with preliminary evidence of greater efficacy after repeat injection. A phase III trial is ongoing.Clinical Trial Identifier: ClinicalTrials.gov: NCT03613662.Keywords: epidural steroid injections, lubosacral radicuar pain, sciatica, neuropathic pain

Background: COVID-19 has caused a worldwide pandemic, making the early detection of the virus crucial. We present an approach for the determination of COVID-19 infection based on breath analysis. Methods: A high sensitivity mass spectrometer was combined with artificial intelligence and used to develop a method for the identification of COVID-19 in human breath within seconds. A set of 1137 positive and negative subjects from different age groups, collected in two periods from two hospitals in the USA, from 26 August, 2020 until 15 September, 2020 and from 11 September, 2020 until 11 November, 2020, was used for the method development. The subjects exhaled in a Tedlar bag, and the exhaled breath samples were subsequently analyzed using a Proton Transfer Reaction Time-of-Flight Mass Spectrometer (PTR-ToF-MS). The produced mass spectra were introduced to a series of machine learning models. 70% of the data was used for these sub-models’ training and 30% was used for testing. Findings: A set of 340 samples, 95 positives and 245 negatives, was used for the testing. The combined models successfully predicted 77 out of the 95 samples as positives and 199 out of the 245 samples as negatives. The overall accuracy of the model was 81.2%. Since over 50% of the total positive samples belonged to the age group of over 55 years old, the performance of the model in this category was also separately evaluated on 339 subjects (170 negative and 169 positive). The model correctly identified 166 out of the 170 negatives and 164 out of the 169 positives. The model accuracy in this case was 97.3%. Interpretation: The results showed that this method for the identification of COVID-19 infection is a promising tool, which can give fast and accurate results.

Abstract Background Expert psychiatrists conducting work disability evaluations often disagree on work capacity (WC) when assessing the same patient. More structured and standardised evaluations focusing on function could improve agreement. The RELY studies aimed to establish the inter-rater reproducibility (reliability and agreement) of ‘functional evaluations’ in patients with mental disorders applying for disability benefits and to compare the effect of limited versus intensive expert training on reproducibility. Methods We performed two multi-centre reproducibility studies on standardised functional WC evaluation (RELY 1 and 2). Trained psychiatrists interviewed 30 and 40 patients respectively and determined WC using the Instrument for Functional Assessment in Psychiatry (IFAP). Three psychiatrists per patient estimated WC from videotaped evaluations. We analysed reliability (intraclass correlation coefficients [ICC]) and agreement (‘standard error of measurement’ [SEM] and proportions of comparisons within prespecified limits) between expert evaluations of WC. Our primary outcome was WC in alternative work (WCalternative.work), 100–0%. Secondary outcomes were WC in last job (WClast.job), 100–0%; patients’ perceived fairness of the evaluation, 10–0, higher is better; usefulness to psychiatrists. Results Inter-rater reliability for WCalternative.work was fair in RELY 1 (ICC 0.43; 95%CI 0.22–0.60) and RELY 2 (ICC 0.44; 0.25–0.59). Agreement was low in both studies, the ‘standard error of measurement’ for WCalternative.work was 24.6 percentage points (20.9–28.4) and 19.4 (16.9–22.0) respectively. Using a ‘maximum acceptable difference’ of 25 percentage points WCalternative.work between two experts, 61.6% of comparisons in RELY 1, and 73.6% of comparisons in RELY 2 fell within these limits. Post-hoc secondary analysis for RELY 2 versus RELY 1 showed a significant change in SEMalternative.work (− 5.2 percentage points WCalternative.work [95%CI − 9.7 to − 0.6]), and in the proportions on the differences ≤ 25 percentage points WCalternative.work between two experts (p = 0.008). Patients perceived the functional evaluation as fair (RELY 1: mean 8.0; RELY 2: 9.4), psychiatrists as useful. Conclusions Evidence from non-randomised studies suggests that intensive training in functional evaluation may increase agreement on WC between experts, but fell short to reach stakeholders’ expectations. It did not alter reliability. Isolated efforts in training psychiatrists may not suffice to reach the expected level of agreement. A societal discussion about achievable goals and readiness to consider procedural changes in WC evaluations may deserve considerations.

Kevin

Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970s and 80s. However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies.

The article presents the German case of creating and managing theso called integrated health care systems. It is supposed to solve theproblem of fragmentation and lack of cooperation, which is costlyand causes difficulties to patients. The case shows that holisticthinking is better, but it requires dramatic changes in attitudes andbehavior of medical professionals and managers in both hospitalsand the government.

The article in the British Journal of Haematology discusses the treatment of refractory severe idiopathic immune thrombocytopenia (ITP) with daratumumab, an anti-CD38 antibody. The study reports on a case series of seven patients who received daratumumab treatment, with four patients achieving sustained complete remission. The findings suggest that daratumumab may be a valid treatment option for refractory ITP patients, leading to durable responses in some cases. Additional data from prospective clinical trials are needed to further evaluate the efficacy of daratumumab in treating ITP. [Extracted from the article]

This paper presents a comparative analysis of the blind test outcomes of two independent methods for the identification of tropical wood species in pulp and paper products. Both, the established anatomical and the relatively new chemotaxonomic method support the European Deforestation Regulation 2023/1115 (EUDR), which aims to ensure that only legally harvested timber that has not contributed to deforestation is traded in the EU. The blind test involved 570 decisions on 15 test sheets of 37 self-manufactured mixed tropical hardwood pulps and an industrial beech pulp, used as a matrix. Both detection techniques demonstrated robust performance with over 80 % hit rates. The results show that the synergies and combination of the strengths of both methods can be utilized and lead to even better combined performance. In order to establish the chemotaxonomic identification method as a complement to the conventional anatomy-based method, statistical analyses were performed to assess its intermediate precision between three different GC-MS systems. In most cases, the method gave consistent results independent of the instrument used. [ABSTRACT FROM AUTHOR]

Interdisciplinary approaches are needed to reconstruct the behaviour of glaciers beyond the beginning of systematic measurements. For example, historical documents have been used to reconstruct former glacier extents successfully at different sites, including in the well-documented Mont Blanc area that became popular since the mid-18th century among artists, scientists, and travellers. Jean-Antoine Linck from Geneva is probably the artist to whom we owe the greatest number of unique glacier views. Linck’s special preference were the ice regions, which he discovered and drew with alpinistic daring and naturalistic correctness, preferably by gouache, although many pencil sketches are preserved. Linck subtly used the etching technique to create easily reproducible plates in large format, which are then hand-coloured with gouache and watercolour. This technique allowed him to create numerous reproductions of the same view, while still giving them a unique and original aspect, views that are remarkable for their serenity and silence, while offering luminous atmospheres. These illustrations introduced the realistic representation of the high mountains into the iconography of Genevese painting and thus led to a new kind of landscape painting with a permanent character. From a perspective of glacier history and although many of his artworks are not exactly dated by the author, the work of Jean-Antoine Linck is indispensable since it represents the whole development, specifically of the Mer de Glace and the Glacier des Bossons, but also other glaciers during the period from the end of the 18th century until the 19th century glacier maximum around 1820. Linck’s work has the same importance for the Mont Blanc area as that of Caspar Wolf and Samuel Birmann for the central Swiss Alps or Thomas Ender for the Austrian Alps in terms of glacier iconography. Therefore, Linck was both an artist and a glacier historian.

Des approches interdisciplinaires sont nécessaires pour reconstruire les fluctuations des glaciers au xixe siècle, au-delà du début des mesures systématiques. Par exemple, des documents historiques ont été appliqués pour reconstituer d’anciennes étendues des glaciers sur différents sites, notamment dans la région du Mont-Blanc, qui sont très bien documentés et devenus populaires parmi les artistes, les scientifiques et les voyageurs depuis le milieu du xviiie siècle. Le Genevois Jean-Antoine Linck est probablement l’artiste à qui l’on doit le plus de vues glaciaires exceptionnelles. La préférence particulière de Linck était les régions des glaciers, qu’il a découvertes et dessinées avec une audace d’alpiniste et une exactitude de naturaliste, principalement à la gouache, bien que de nombreux croquis au crayon aient été conservés. Linck a subtilement utilisé la technique de la gravure pour créer des planches de grand format facilement reproductibles, qui ont été ensuite coloriées à la gouache et à l’aquarelle. Cette technique lui a permis de créer de nombreuses reproductions d’une même vue, tout en leur donnant un aspect unique et original. Elles sont remarquables de sérénité et de silence, tout en offrant des ambiances lumineuses. Ces illustrations introduisent la représentation réaliste de la haute montagne dans l’iconographie de la peinture genevoise et conduisent ainsi à une nouvelle forme de peinture de paysage à caractère permanent. D’un point de vue de l’histoire des glaciers, et bien que nombre de ses œuvres ne soient pas exactement datées par l’auteur, l’ouvrage de Jean-Antoine Linck est indispensable. Il représente l’ensemble de l’évolution de la mer de Glace et du glacier des Bossons, mais également d’autres glaciers, pendant la période allant de la fin du xviiie siècle jusqu’au maximum glaciaire du xixe siècle vers 1820. L’œuvre de Linck accorde au territoire du Mont-Blanc la même importance, en termes d’iconographie des glaciers, que celle de Caspar Wolf et Samuel Birmann pour les Alpes centrales suisses, ou de Thomas Ender pour les Alpes autrichiennes. Linck était donc à la fois artiste et historien des glaciers.reconstitutions glaciaires, iconographie, Jean-Antoine Linck, région du Mont-Blanc, Petit âge glaciaire