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Small unmanned aerial systems (sUASs) are becoming very popular as affordable and reliable observation platforms. The Lower Atmospheric Process Studies at Elevation – a Remotely-piloted Aircraft Team Experiment (LAPSE-RATE), conducted in the San Luis Valley (SLV) of Colorado (USA) between 14 and 20 July 2018, gathered together numerous sUASs, remote-sensing equipment, and ground-based instrumentation. Flight teams from the Finnish Meteorological Institute (FMI) and the Kansas State University (KSU) co-operated during LAPSE-RATE to measure and investigate the properties of aerosol particles and gases at the surface and in the lower atmosphere. During LAPSE-RATE the deployed instrumentation operated reliably, resulting in an observational dataset described below in detail. Our observations included aerosol particle number concentrations and size distributions, concentrations of CO2 and water vapor, and meteorological parameters. All datasets have been uploaded to the Zenodo LAPSE-RATE community archive (https://zenodo.org/communities/lapse-rate/, last access: 21 August 2020). The dataset DOIs for FMI airborne measurements and surface measurements are available here: https://doi.org/10.5281/zenodo.3993996, Brus et al. (2020a), and those for KSU airborne measurements and surface measurements are available here: https://doi.org/10.5281/zenodo.3736772, Brus et al. (2020b).

Unmanned aerial systems (UASs) are increasingly being used as observation platforms for atmospheric applications. The Lower Atmospheric Process Studies at Elevation – a Remotely-piloted Aircraft Team Experiment (LAPSE-RATE) in Alamosa, Colorado, USA, on 14–20 July 2018 investigated and validated different UASs, measurement sensors and setup configurations. Flight teams from the Finnish Meteorological Institute (FMI) and Kansas State University (KSU) participated in LAPSE-RATE to measure and investigate properties of aerosol particles and gases in the lower atmosphere. During the experiment, the performance of different UAS configurations were investigated and confirmed to operate reliably, resulting in a scientifically sound observational dataset. As an example, concentration of aerosols – including two new particle formation events, CO2 and water vapor, and meteorological parameters in the atmospheric vertical profile were measured during the short experiment. Such observations characterizing atmospheric phenomena of this specific environment would have not been possible in any other way and, thus, demonstrate the power of UASs as new, promising tools in atmospheric and environmental research.

IntroductionPrevious studies reported that the coronavirus disease (COVID-19) pandemic has negatively affected the mental health of employees in the hospitality industry internationally, however, its effect in Sweden has not been studied. Unlike several other countries, Sweden never enforced a lockdown. Restaurants, bars, and hotels could remain open and host a limited number of guests but had to abide by certain restrictions.MethodsA cross-sectional survey was distributed among hospitality industry employees containing questions regarding the perceived effects of the pandemic on the respondents’ working and life situations and their physical and psychological health. The sample consisted of 699 individuals, with a response rate of 47.9%.ResultsAlthough several respondents had been laid off or furloughed, the majority of the sample remained at the same employer. However, more than half of the respondents reported that their economic situation had deteriorated. Compared to before the pandemic, 38.1% experienced elevated levels of stress, 48.3% experienced elevated levels of worry, and 31.4% reported worsened mood. A deteriorating personal economy and difficulty in following COVID-19-related restrictions at work were associated with the worsening of these three mental health aspects. While the fear of becoming infected with COVID-19 was related to higher levels of stress, the fear of infecting others was related to higher levels of worry.ConclusionAlthough Sweden imposed less strict measures than most other countries, the personal economy and mental health of hospitality workers were negatively affected by the COVID-19 pandemic.

A full-thickness biopsy of the bowel wall is required to evaluate the enteric nervous system. A patient with aggravating gastrointestinal symptoms underwent a laparoscopic full-thickness biopsy of the ileum and, 1 year later, an endoscopic full-thickness biopsy of the sigmoid colon. Both samples showed enteric neuropathy characterized by vacuolated and enlarged neurons. The length of the myenteric plexus was greater in the endoscopic (23 mm) compared to the laparoscopic (11 mm) biopsy, with fewer tissue artefacts in the laparoscopic approach. Clinical deterioration was paralleled by enteric neuropathy with an increase in the percentage of vacuolated and enlarged enteric neurons from 24 to 35%.

The hygroscopicity of mineral aerosol samples has been examined by three independent methods: diffuse reflectance infrared Fourier transform spectroscopy, thermogravimetric analysis and differential mobility analysis. All three methods allow an evaluation of the water coverage of two samples, CaCO3 and Arizona Test dust, as a function of relative humidity. For the first time, a correlation between absolute gravimetric measurements and the other two (indirect) methods has been established. Water uptake isotherms were reliably determined for both solids which at 298 K and 80% relative humidity exhibited similar coverages of ~4 monolayers. However, the behaviour at low relative humidity was markedly different in the two cases, with Arizona Test Dust showing a substantially higher affinity for water in the contact layer. This is understandable in terms of the chemical composition of these two materials. The mobility analysis results are in good accord with field observations and with our own spectroscopic and gravimetric measurements. These findings are of value for an understanding of atmospheric chemical processes.

BACKGROUND: Microscopic colitis (MC) is a disease manifested by diarrhoea and is divided into collagenous and lymphocytic colitis. The aetiology is unknown, but auto-immunity is suggested. Auto-antibodies have been only rarely examined in this entity. The aim of the study was to examine the prevalence of auto-antibodies, and to examine associations between the presence of antibodies and clinical findings. METHODS AND FINDINGS: Women with MC verified by biopsy and younger than 73 years, at any Department of Gastroenterology, in the district of Skåne, between 2002 and 2010 were invited to participate in this study. The patients were asked to complete both a questionnaire describing their medical history and the Gastrointestinal Symptom Rating Scale (GSRS). Blood samples were collected. Anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), and antibodies against glutamic acid decarboxylase (anti-GAD), islet antigens-like insulin 2 (anti-IA2), thyroid peroxidase (anti-TPO), and thyrotropin receptor (TRAK) were analysed. Of 240 women identified, 133 were finally included in the study, median age 63 (59-67) years. Apart from the MC diagnosis, 52% also suffered from irritable bowel syndrome, 31% from hypertension and 31% from allergy. The prevalence of ANA (14%), ASCA IgG (13%), and anti-TPO antibodies (14%) for these patients was slightly higher than for the general population, and were found together with other concomitant diseases. Patients had more of all gastrointestinal symptoms compared with norm values, irrespective of antibody expression. CONCLUSIONS: Women with MC have a slightly increased prevalence of some auto-antibodies. These antibodies are not associated with symptoms, but are expressed in patients with concomitant diseases, obscuring the pathophysiology and clinical picture of MC.

Background and aims. Microscopic colitis (MC), predominantly affecting women, is associated with thyroid disorders, although purely defined of which type, or compared with controls. Its association with subclinical thyroid disorders, and related increased risk of cardiovascular diseases, has never been examined. The aim was to examine the prevalence of autoantibodies and subclinical and clinical thyroid dysfunction in female patients with MC compared with controls. Methods. Women younger than 73 years old with biopsy-verified MC from the Department of Gastroenterology in Skane, during 2002-2010, were invited. Out of 240 identified, 133 were finally included. A questionnaire about medical history was completed and blood samples were collected. Serum was analyzed for free thyroxin and triiodothyronine, thyroid-stimulating hormone and antithyroid peroxidase (anti-TPO) antibodies. A population-based group of 737 women served as controls. Result. The prevalence of thyroid disorders in patients was higher compared to controls [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.78-4.99], but the prevalence of subclinical disorders was not different (OR= 1.18, 95% CI = 0.48-2.85). Anti-TPO antibodies were present in 10.6% of MC patients and 18.6% of controls. Twenty-five MC patients had hypothyroidism: 15 with Hashimotos hypothyroidism, 6 with completed treatment of thyrotoxicosis and 4 with completed surgery after nontoxic goiter. Conclusion. Thyroid disorders, autoimmune hypothyroidism being most frequent, are more prevalent in patients with MC than in controls, whereas the prevalence of subclinical thyroid disorders in MC patients does not differ significantly from controls. [ABSTRACT FROM AUTHOR]

Mitochondrial 26-hydroxylation of exogenous cholesterol, endogenous cholesterol, and 5β-cholestane-3α,7α,12α-triol was studied. 26-Hydroxylation of endogenous cholesterol was measured by mass fragmentography. NADPH and isocitrate stimulated 26-hydroxylation of endogenous as well as exogenous cholesterol. 26-Hydroxylation of endogenous cholesterol was linear with time for 15 min, whereas that of exogenous cholesterol was linear with time for at least 40 min. This finding indicates that the fractions of exogenous and endogenous cholesterol that were 26-hydroxylated did not equilibrate. Mg2+ stimulated isocitrate- and NADPH-dependent 26-hydroxylation of exogenous cholesterol but inhibited in the case of endogenous cholesterol. Ca2+ stimulated NADPH-dependent and inhibited isocitrate-dependent 26-hydroxylation of both exogenous and endogenous cholesterol. It is suggested that the differing effect of Mg2+ on the 26-hydroxylation of exogenous and endogenous cholesterol is related to transfer of the steroid to the enzyme. Isocitrate- and NADPH-dependent 26-hydroxylation of exogenous 5β-cholestane-3α,7α,12α-triol differed from that of exogenous cholesterol in response to Mg2+ and Ca2+. 26-Hydroxylation of 5β-cholestane-3α,7α,12α-triol was stimulated by Mg2+ in low concentrations but inhibited by Mg2+ and Ca2+ in high concentrations. Mg2+ had the same influence on the 26-hydroxylation of three dioxygenated C27-steroids known to be intermediates in bile acid biosynthesis. The results are not only compatible with heterogeneity of the mitochondrial 26-hydroxylase system but also with differences in the transport of cholesterol and 5β-cholestane-3α,7α,12α-triol to the enzyme. The finding of a differing effect of Mg2+ on 26-hydroxylation of exogenous and endogenous cholesterol seems to favor differences in transport rather than heterogeneity of the 26-hydroxylase as an explanation of the results.

The effect of biliary obstruction on side chain hydroxylations in the biosynthesis and metabolism of bile acids was studied in the rat. For comparison, several other hydroxylation reactions in bile acid biosynthesis and metabolism were assayed. Biliary obstruction inhibited microsomal 26-hydroxylation of 5β-cholestane-3α,7α-diol and microsomal 25- and 26-hydroxylation of 5β-cholestane-3α,7α-12α-triol. Microsomal 7α-hydroxylation of cholesterol and 6β-hydroxylation of lithocholic acid acid increased significantly, whereas the increase in microsomal 12α-hydroxylation of 5β-cholestane-3α,7α-diol was less. Mitochondrial 26-hydroxylation of cholesterol, 5-cholestene-3β,7α-diol, and 7α-hydroxy-4-cholesten-3-one was stimulated, whereas 26-hydroxylation of 5β-cholestane-3α,7α-diol was not affected and that of 5β-cholestane-3α,7α,12α-triol was markedly inhibited. The results indicate that mitochondrial 26-hydroxylation, particularly of substrates that primarily are precursors of chenodeoxycholic acid, plays a more important role in bile acid biosynthesis under conditions of biliary obstruction than under normal conditions.

The present study was designed to obtain more definitive information in man on the metabolic pathways to chenodeoxycholic acid and to cholic acid via a pathway not involving an initial 7 alpha-hydroxylation of cholesterol. Four bile fistula patients were administered consecutively two or more of the following 3H-labeled bile acid intermediates: 7 alpha-hydroxycholesterol, 7 alpha-hydroxy-4-cholesten-3-one, 5 beta-cholestane 3 alpha,7 alpha,26-triol, 26-hydroxycholesterol,7 alpha,26-dihydroxy-4-cholesten-3-one, and 5-cholestene-3 beta,12 alpha-diol. Both 7 alpha-hydroxy[7 beta-3H]cholesterol and 7 alpha-hydroxy-4-[6 beta-3H]cholesten-3-one were efficiently converted to bile acids and preferred chenodeoxycholic acid over cholic acid. The specific activity time curves indicated that a portion of cholic acid synthesis did not pass through 7 alpha-hydroxycholesterol. [3H]26-Hydroxycholesterol and [3H]-5-cholestene 3 beta,12 alpha-diol, two potential intermediates of this bypass pathway to cholic acid, were poorly converted to primary bile acids (10 to 27%). The [3H]26-hydroxycholesterol preferred chenodeoxycholic over cholic acid by about 4 to 1. The [3H]5-cholestene 3 beta,12 alpha-diol formed cholic acid in low yield (10 to 20%). It is concluded that pathways to primary acids from cholesterol through 26-hydroxycholesterol and 5-cholestene 3 beta,12 alpha-diol are probably of minor quantitative significance. A selective pathway to chenodeoxycholic acid via 26-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one was also investigated. The 5 beta-cholestane 3 alpha,7 alpha,26-triol was converted in about equal amounts to cholic and chenodeoxycholic acids. The 7 alpha-hydroxy-4-cholesten-3-one was also efficiently converted to both bile acids but preferred chemodeoxycholic acid. The most efficient precursor of chenodeoxycholic acid was 7 alpha,26-dihydroxy-4-cholesten-3-one, which was efficiently converted to primary bile acids; chenodeoxycholic acid was preferred over cholic acid by approximately 7 to 1. These findings suggest the presence of a major pathway to chenodeoxycholic acid via the 26-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one and intermediate formation of 7 alpha,26-dihydroxy-4-cholesten-3-one.

The metabolism of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid was studied in the bile fistula rats and in preparations from rat liver homogenates. In the bile fistula rats, the main products were chenodeoxycholic acid, alpha-muricholic acid, and beta-muricholic acid. Only small amounts of cholic acid were formed. Incubations of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid with microsomes and NADPH yielded as the main product 3 alpha, 6 beta, 7 alpha-trihydroxy-5 beta-cholestanoic acid. The formation of small amounts of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid was shown. The major product in incubations of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid with microsomes and the 100,000 g supernatant fluid fortified with ATP was identified as 3 alpha, 7 alpha, 24 xi-trihydroxy-5 beta-cholestanoic acid. This compound was converted into chenodeoxycholic acid and its metabolites in the bile fistula rat.

Several hydroxylase activities in bile acid biosynthesis were assayed in subcellular fractions of human fetal liver. The livers were obtained at legal abortions performed between gestational weeks 14 and 24. Microsomal 12 alpha-hydroxylase and mitochondrial 12 alpha- and 26-hydroxylase activities were detected from week 14. The microsomal fraction also had capacity for 25-hydroxylation, whereas 7 alpha- and 26-hydroxylase activities were hardly detectable. The variation of the hydroxylase activities between different experiments can be explained by inactivation during the abortion or workup procedure. The results are discussed with respect to earlier studies of bile acid biosynthesis during development and adult life.

Background: The aim was to compare bias and precision for 177 Lu-SPECT activity-concentration estimation using a dual-headed Anger SPECT system and a ring-configured CZT SPECT system. This was investigated for imaging at 208 keV and 113 keV, respectively., Methods: Phantom experiments were performed on a GE Discovery 670 system with 5/8'' NaI(Tl) crystal (dual-headed Anger system) and a GE StarGuide (ring-configured CZT system). Six spheres (1.2 mL to 113 mL) in a NEMA PET body phantom were filled with 99m Tc and 177 Lu, separately. Mean relative errors and coefficients of variation (CV) in estimated sphere activity concentration were studied over six timeframes of 10 min each for the two systems. For 177 Lu, similar acquisitions were also performed for an anthropomorphic phantom with two spheres (10 mL and 25 mL) in a liver with non-radioactive background and a sphere-to-background ratio of 15:1. Tomographic reconstruction was performed using OS-EM with 10 subsets with compensation for attenuation, scatter, and distance-dependent spatial resolution. For the Anger system, up to 40 iterations were used and for the ring-configured CZT system up to 30 iterations were used., Results: The two systems showed similar mean relative errors and CVs for 177 Lu when using an energy window around 208 keV, while the ring-configured system demonstrated a lower bias for a similar CV compared to the Anger system for 99m Tc and for 177 Lu when using an energy window around 113 keV. However, total activity in the phantom tended to be overestimated in both systems for these cases., Conclusions: The ring-configured CZT system is a viable alternative to the dual-headed Anger system equipped with medium-energy collimators for 177 Lu-SPECT and shows a potential advantage for activity-concentration estimation when operated at 113 keV. However, further consideration of the preservation of total activity is warranted., (© 2024. The Author(s).)

The genomic signature of an organism captures the characteristics of repeated oligonucleotide patterns in its genome 1 , such as oligomer frequencies, GC content, and differences in codon usage. Viruses, however, are obligate intracellular parasites that are dependent on their host cells for replication, and information about genomic signatures in viruses has hitherto been sparse.Here, we investigate the presence and specificity of genomic signatures in 2,768 eukaryotic viral species from 105 viral families, aiming to illuminate dependencies and selective pressures in viral genome evolution. We demonstrate that most viruses have highly specific genomic signatures that often also differ significantly between species within the same family. The species-specificity is most prominent among dsDNA viruses and viruses with large genomes. We also reveal consistent dissimilarities between viral genomic signatures and those of their host cells, although some viruses present slight similarities, which may be explained by genetic adaptation to their native hosts. Our results suggest that significant evolutionary selection pressures act upon viral genomes to shape and preserve their genomic signatures, which may have implications for the field of synthetic biology in the construction of live attenuated vaccines and viral vectors., (© 2024. The Author(s).)

The term 'RNA-seq' refers to a collection of assays based on sequencing experiments that involve quantifying RNA species from bulk tissue, single cells or single nuclei. The kallisto, bustools and kb-python programs are free, open-source software tools for performing this analysis that together can produce gene expression quantification from raw sequencing reads. The quantifications can be individualized for multiple cells, multiple samples or both. Additionally, these tools allow gene expression values to be classified as originating from nascent RNA species or mature RNA species, making this workflow amenable to both cell-based and nucleus-based assays. This protocol describes in detail how to use kallisto and bustools in conjunction with a wrapper, kb-python, to preprocess RNA-seq data. Execution of this protocol requires basic familiarity with a command line environment. With this protocol, quantification of a moderately sized RNA-seq dataset can be completed within minutes., (© 2024. Springer Nature Limited.)

Background: The aim was to investigate the noise and bias properties of quantitative 177 Lu-SPECT with respect to the number of projection angles, and the number of subsets and iterations in the OS-EM reconstruction, for different total acquisition times., Methods: Experimental SPECT acquisition of six spheres in a NEMA body phantom filled with 177 Lu was performed, using medium-energy collimators and 120 projections with 180 s per projection. Bootstrapping was applied to generate data sets representing acquisitions with 20 to 120 projections for 10 min, 20 min, and 40 min, with 32 noise realizations per setting. Monte Carlo simulations were performed of 177 Lu-DOTA-TATE in an anthropomorphic computer phantom with three tumours (2.8 mL to 40.0 mL). Projections representing 24 h and 168 h post administration were simulated, each with 32 noise realizations. Images were reconstructed using OS-EM with compensation for attenuation, scatter, and distance-dependent resolution. The number of subsets and iterations were varied within a constrained range of the product number of iterations × number of projections ≤ 2400 . Volumes-of-interest were defined following the physical size of the spheres and tumours, the mean activity-concentrations estimated, and the absolute mean relative error and coefficient of variation (CV) over noise realizations calculated. Pareto fronts were established by analysis of CV versus mean relative error., Results: Points at the Pareto fronts with low CV and high mean error resulted from using a low number of subsets, whilst points at the Pareto fronts associated with high CV but low mean error resulted from reconstructions with a high number of subsets. The number of projection angles had limited impact., Conclusions: For accurate estimation of the 177 Lu activity-concentration from SPECT images, the number of projection angles has limited importance, whilst the total acquisition time and the number of subsets and iterations are parameters of importance., (© 2024. The Author(s).)

Purpose: Gender differences have been found in the outcomes of vocational rehabilitation (VR) and in Supported Employment (SE), therefore, the purpose of this study was to explore employment specialists' (ES) social representations of gender in relation to work and VR and how these social representations influence the ES's work in the VR process according to SE., Methods: The qualitative method of focus group discussions was employed. Ten focus groups were held with 39 ESs from four categories of SE organizations in Sweden. Topic analysis was applied to the transcribed material from the focus groups., Results: Five themes with different social representations about gender and disability in relation to VR and working life formed in the analysis: (1) differences in personal and health factors among VR-participants, (2) gender norms in society influencing VR, (3) energy-intensive environmental issues influencing VR, (4) gender-specific interactions in VR, and (5) gendered paths in the welfare system., Conclusion: Social representations of higher strains on women with disabilities compared to men with disabilities both in private and working life, which reflect the lived experiences of the ESs, is a possible explanation for gender differences in VR and working life for persons with disabilities.IMPLICATIONS FOR REHABILITATIONGender differences in the outcomes of vocational rehabilitation (VR) interventions have been noticed worldwide. In this study, pervasive social representations about gender and disability in relation to VR were found, but also unconsciousness about gender among VR professionals. Therefore, awareness of gender is necessary in VR.Individualized and person-centered approaches to VR like Supported Employment, although considered best practice, might hide structures like gender, which could lead to reproducing discriminating processes and therefore not achieving gender equality in VR. Therefore, knowledge of discrimination is important in VR.Gender-sensitivity in vocational rehabilitation models with a person-centered and individualized approach is needed and there might also be a need to systematically tailor vocational rehabilitation models to reach gender equality in the outcomes of the interventions. Therefore, gender equality indicators are needed for VR models, to evaluate model effectiveness from a gender perspective.

Peptide receptor radionuclide therapy presents the possibility of tracing and quantifying the uptake of the drug in the body and performing dosimetry, potentially allowing individualization of treatment schemes. However, the details of how neuroendocrine tumors (NETs) respond to different absorbed doses are insufficiently known. Here, we investigated the relationship between tumor-absorbed dose and tumor response in a cohort of patients with NETs treated with [ 177 Lu]Lu-DOTATATE. Methods: This was a retrospective study based on 69 tumors in 32 patients treated within a clinical trial. Dosimetry was performed at each cycle of [ 177 Lu]Lu-DOTATATE, rendering 366 individual absorbed dose assessments. Hybrid planar-SPECT/CT imaging using [ 177 Lu]Lu-DOTATATE was used, including quantitative SPECT reconstruction, voxel-based absorbed dose rate calculation, semiautomatic image segmentation, and partial-volume correction. Changes in tumor volume were used to determine tumor response. The volume for each tumor was manually delineated on consecutive CT scans, giving a total of 712 individual tumor volume assessments. Tumors were stratified according to grade. The relationship between absorbed dose and response was investigated using mixed-effects models and logistic regression. Tumors smaller than 4 cm 3 were excluded. Results: In grade 2 NETs, a clear relationship between absorbed dose and volume reduction was observed. Our observations suggest a 90% probability of partial tumor response for an accumulated tumor-absorbed dose of at least 135 Gy. Conclusion: Our findings are in accordance with previous observations regarding the relationship between tumor shrinkage and absorbed dose. Moreover, our data suggest an absorbed dose threshold for partial response in grade 2 NETs. These observations provide valuable insights for the design of dosimetry-guided peptide receptor radionuclide therapy schemes., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Although the importance of quantitative SPECT has increased tremendously due to newly developed therapeutic radiopharmaceuticals, there are still no accreditation programs to harmonize SPECT imaging. Work is currently underway to develop an accreditation for quantitative 177 Lu SPECT/CT. The aim of this study is to verify whether the positioning of the spheres within the phantom has an influence on the recovery and thus needs to be considered in SPECT harmonization. In addition, the effects of these recovery coefficients on a potential partial volume correction as well as absorbed-dose estimates are investigated., Methods: Using a low-dose CT of a SPECT/CT acquisition, a computerized version of the NEMA body phantom was created using a semi-automatic threshold-based method. Based on the mass-density map, the detector orbit, and the sphere centers, realistic SPECT acquisitions of all possible 720 sphere configurations of both the PET and the SPECT versions of the NEMA Body Phantom were generated using Monte Carlo simulations. SPECT reconstructions with different numbers of updates were performed without (CASToR) and with resolution modeling (STIR). Recovery coefficients were calculated for all permutations, reconstruction methods, and phantoms, and their dependence on the sphere positioning was investigated. Finally, the simulation-based findings were validated using SPECT/CT acquisitions of six different sphere configurations., Results: Our analysis shows that sphere positioning has a significant impact on the recovery for both of the reconstruction methods and the phantom type. Although resolution modeling resulted in significantly higher recovery, the relative variation in recovery within the 720 permutations was even larger. When examining the extreme values of the recovery, reconstructions without resolution modeling were influenced primarily by the sphere position, while with resolution modeling the volume of the two adjacent spheres had a larger influence. The SPECT measurements confirmed these observations, and the recovery curves showed good overall agreement with the simulated data., Conclusion: Our study shows that sphere positioning has a significant impact on the recovery obtained in NEMA sphere phantom measurements and should therefore be considered in a future SPECT accreditation. Furthermore, the single-measurement method normally performed for PVC should be reconsidered to account for the position dependency., (© 2024. The Author(s).)

Purpose: The aim of the current study was to explore the construct validity and internal consistency reliability of the International Classification of Functioning, Disability and Health (ICF)-based original English version of the Hearing and Functioning in Everyday Life Questionnaire (HFEQ) and to revise the HFEQ based on the results., Method: This study used a cross-sectional survey design. The data were collected using an online survey. Adults with self-reported hearing disability ( n = 513) from the United States were included. The ICF components of body functions, activity and participation, and environmental factors were tested as the underlying structure of the HFEQ using confirmatory factor analysis and then adjusted by triangulation with previous content validation., Results: The results of the current study confirmed the ICF components of body functions, activity and participation, and environmental factors as underlying constructs of the HFEQ. However, after triangulation with previous content validation, fine adjustments were made. The revised version of the HFEQ includes two removed items and a fine-tuned factor structure., Conclusion: The results confirm that the structure of the HFEQ aligns with the ICF, and the overall results indicate that HFEQ has acceptable construct validity and internal consistency.

With the development of new radiopharmaceutical therapies, quantitative SPECT/CT has progressively emerged as a crucial tool for dosimetry. One major obstacle of SPECT is its poor resolution, which results in blurring of the activity distribution. Especially for small objects, this so-called partial-volume effect limits the accuracy of activity quantification. Numerous methods for partial-volume correction (PVC) have been proposed, but most methods have the disadvantage of assuming a spatially invariant resolution of the imaging system, which does not hold for SPECT. Furthermore, most methods require a segmentation based on anatomic information. Methods: We introduce DL-PVC, a methodology for PVC of 177 Lu SPECT/CT imaging using deep learning (DL). Training was based on a dataset of 10,000 random activity distributions placed in extended cardiac-torso body phantoms. Realistic SPECT acquisitions were created using the SIMIND Monte Carlo simulation program. SPECT reconstructions without and with resolution modeling were performed using the CASToR and STIR reconstruction software, respectively. The pairs of ground-truth activity distributions and simulated SPECT images were used for training various U-Nets. Quantitative analysis of the performance of these U-Nets was based on metrics such as the structural similarity index measure or normalized root-mean-square error, but also on volume activity accuracy, a new metric that describes the fraction of voxels in which the determined activity concentration deviates from the true activity concentration by less than a certain margin. On the basis of this analysis, the optimal parameters for normalization, input size, and network architecture were identified. Results: Our simulation-based analysis revealed that DL-PVC (0.95/7.8%/35.8% for structural similarity index measure/normalized root-mean-square error/volume activity accuracy) outperforms SPECT without PVC (0.89/10.4%/12.1%) and after iterative Yang PVC (0.94/8.6%/15.1%). Additionally, we validated DL-PVC on 177 Lu SPECT/CT measurements of 3-dimensionally printed phantoms of different geometries. Although DL-PVC showed activity recovery similar to that of the iterative Yang method, no segmentation was required. In addition, DL-PVC was able to correct other image artifacts such as Gibbs ringing, making it clearly superior at the voxel level. Conclusion: In this work, we demonstrate the added value of DL-PVC for quantitative 177 Lu SPECT/CT. Our analysis validates the functionality of DL-PVC and paves the way for future deployment on clinical image data., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Aim: We aimed to evaluate the occurrence of, and risk factors for precocious and early puberty in a retrospective cohort study of girls with shunted infantile hydrocephalus., Methods: The study population comprised 82 girls with infantile hydrocephalus, born between 1980 and 2002, and treated with a ventriculoperitoneal shunt. Data were available for 39 girls with myelomeningocele and 34 without. Medical records were analysed regarding clinical data and timing of puberty. Precocious and early puberty was defined as the appearance of pubertal signs before 8 years and 0 months and 8 years and 9 months, respectively., Results: Median age at last admission was 15.8 years (range 10.0-18.0). In total, 15 girls (21%) had precocious puberty, and another 21 (29%) had early puberty. Three or more shunt revisions had been performed in 26/36 girls with early or precocious puberty and in 3/37 girls without (p = 0.01). The number of shunt revisions correlated negatively with age at the start of puberty in the girls with myelomeningocele (Spearman's correlation coefficient = -0.512, p = 0.001)., Conclusion: Girls with shunted infantile hydrocephalus have a high risk of precocious or early puberty. Repeated shunt revisions seemed to be associated with early puberty., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Purpose: The aim was to investigate the use of multiple small VOIs for kidney dosimetry in [ 177 Lu]Lu-DOTA-TATE therapy., Method: The study was based on patient and simulated SPECT images in anthropomorphic geometries. Images were reconstructed using two reconstruction programs (local LundaDose and commercial Hermia) using OS-EM with and without resolution recovery (RR). Five small VOIs were placed to determine the average activity concentration (AC) in each kidney. The study consisted of three steps: (i) determination of the number of iterations for AC convergence based on simulated images; (ii) determination of recovery-coefficients (RCs) for 2 mL VOIs using a separate set of simulated images; (iii) assessment of operator variability in AC estimates for simulated and patient images. Five operators placed the VOIs, using for guidance: a) SPECT/CT with RR, b) SPECT/CT without RR, and c) CT only. For simulated images, time-integrated ACs (TIACs) were evaluated. For patient images, estimated ACs were compared with results of a previous method based on whole-kidney VOIs., Results: Eight iterations and ten subsets were sufficient for both programs and reconstruction settings. Mean RCs (mean ± SD) with RR were 1.03 ± 0.02 (LundaDose) and 1.10 ± 0.03 (Hermia), and without RR 0.91 ± 0.03 (LundaDose) and 0.94 ± 0.03 (Hermia). Most stable and accurate estimates of the AC were obtained using five 2-mL VOIs guided by SPECT/CT with RR, applying them to images without RR, and including an explicit RC for recovery correction., Conclusion: The small VOI method based on five 2-mL VOIs was found efficient and sufficiently accurate for kidney dosimetry in [ 177 Lu]Lu-DOTA-TATE therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Single-cell technologies have been widely used in biological studies and generated a plethora of single-cell data to be interpreted. Due to the inclusion of the priori metabolic network knowledge as well as gene-protein-reaction associations, genome-scale metabolic models (GEMs) have been a powerful tool to integrate and thereby interpret various omics data mostly from bulk samples. Here, we first review two common ways to leverage bulk omics data with GEMs and then discuss advances on integrative analysis of single-cell omics data with GEMs. We end by presenting our views on current challenges and perspectives in this field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Genome-scale metabolic models (GEMs) are computational representations that enable mathematical exploration of metabolic behaviors within cellular and environmental constraints. Despite their wide usage in biotechnology, biomedicine and fundamental studies, there are many phenotypes that GEMs are unable to correctly predict. GECKO is a method to improve the predictive power of a GEM by incorporating enzymatic constraints using kinetic and omics data. GECKO has enabled reconstruction of enzyme-constrained metabolic models (ecModels) for diverse organisms, which show better predictive performance than conventional GEMs. In this protocol, we describe how to use the latest version GECKO 3.0; the procedure has five stages: (1) expansion from a starting metabolic model to an ecModel structure, (2) integration of enzyme turnover numbers into the ecModel structure, (3) model tuning, (4) integration of proteomics data into the ecModel and (5) simulation and analysis of ecModels. GECKO 3.0 incorporates deep learning-predicted enzyme kinetics, paving the way for improved metabolic models for virtually any organism and cell line in the absence of experimental data. The time of running the whole protocol is organism dependent, e.g., ~5 h for yeast., (© 2024. Springer Nature Limited.)

Physiologically based pharmacokinetic (PBPK) models offer the ability to simulate and predict the biodistribution of radiopharmaceuticals and have the potential to enable individualised treatment planning in molecular radiotherapy. The objective of this study was to develop and implement a whole-body compartmental PBPK model for peptide receptor radionuclide therapy (PRRT) with [ 177 Lu]Lu-DOTA-TATE in SimBiology to allow for more complex analyses. The correctness of the model implementation was ensured by comparing its outputs, such as the time-integrated activity (TIA), with those of a PBPK model implemented in SAAM II software., Methods: A combined PBPK model for [ 68 Ga]Ga-DOTA-TATE and [ 177 Lu]Lu-DOTA-TATE was developed and implemented in both SAAM II and SimBiology. A retrospective analysis of 12 patients with metastatic neuroendocrine tumours (NETs) was conducted. First, time-activity curves (TACs) and TIAs from the two software were calculated and compared for identical parameter values. Second, pharmacokinetic parameters were fitted to activity concentrations, analysed and compared., Results: The PBPK model implemented in SimBiology produced TIA results comparable to those generated by the model implemented in SAAM II, with a relative deviation of less than 0.5% when using the same input parameters. The relative deviation of the fitted TIAs was less than 5% when model parameter values were fitted to the measured activity concentrations., Conclusion: The proposed PBPK model implemented in SimBiology can be used for dosimetry in radioligand therapy and TIA prediction. Its outputs are similar to those generated by the PBPK model implemented in SAAM II, confirming the correctness of the model implementation in SimBiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease. This cross-sectional study included 165 children (91 males, median age 6.9 yr range 0.2-17.7 yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen. Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes -45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure. In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: The prevalence of teenage pregnancy in Colombia is higher than the worldwide average. The identification of socio-geographical disparities might help to prioritize public health interventions., Aim: To describe variation in the probability of teenage maternity across geopolitical departments and socio-geographical intersectional strata in Colombia., Methods: A cross-sectional study based on live birth certificates in Colombia. Teenage maternity was defined as a woman giving birth aged 19 or younger. Multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was applied using multilevel Poisson and logistic regression. Two different approaches were used: (1) intersectional: using strata defined by the combination of health insurance, region, area of residency, and ethnicity as the second level (2) geographical: using geopolitical departments as the second level. Null, partial, and full models were obtained. General contextual effect (GCE) based on the variance partition coefficient (VPC) was considered as the measure of disparity. Proportional change in variance (PCV) was used to identify the contribution of each variable to the between-strata variation and to identify whether this variation, if any, was due to additive or interaction effects. Residuals were used to identify strata with potential higher-order interactions., Results: The prevalence of teenage mothers in Colombia was 18.30% (95% CI 18.20-18.40). The highest prevalence was observed in Vichada, 25.65% (95% CI: 23.71-27.78), and in the stratum containing mothers with Subsidized/Unaffiliated healthcare insurance, Mestizo, Rural area in the Caribbean region, 29.08% (95% CI 28.55-29.61). The VPC from the null model was 1.70% and 9.16% using the geographical and socio-geographical intersectional approaches, respectively. The higher PCV for the intersectional model was attributed to health insurance. Positive and negative interactions of effects were observed., Conclusion: Disparities were observed between intersectional socio-geographical strata but not between geo-political departments. Our results indicate that if resources for prevention are limited, using an intersectional socio-geographical approach would be more effective than focusing on geopolitical departments especially when focusing resources on those groups which show the highest prevalence. MAIHDA could potentially be applied to many other health outcomes where resource decisions must be made., (© 2024. The Author(s).)

The energy metabolism of the brain is poorly understood partly due to the complex morphology of neurons and fluctuations in ATP demand over time. To investigate this, we used metabolic models that estimate enzyme usage per pathway, enzyme utilization over time, and enzyme transportation to evaluate how these parameters and processes affect ATP costs for enzyme synthesis and transportation. Our models show that the total enzyme maintenance energy expenditure of the human body depends on how glycolysis and mitochondrial respiration are distributed both across and within cell types in the brain. We suggest that brain metabolism is optimized to minimize the ATP maintenance cost by distributing the different ATP generation pathways in an advantageous way across cell types and potentially also across synapses within the same cell. Our models support this hypothesis by predicting export of lactate from both neurons and astrocytes during peak ATP demand, reproducing results from experimental measurements reported in the literature. Furthermore, our models provide potential explanation for parts of the astrocyte-neuron lactate shuttle theory, which is recapitulated under some conditions in the brain, while contradicting other aspects of the theory. We conclude that enzyme usage per pathway, enzyme utilization over time, and enzyme transportation are important factors for defining the optimal distribution of ATP production pathways, opening a broad avenue to explore in brain metabolism., Competing Interests: Competing interests statement:The authors declare no competing interest.

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation, but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in vivo . Genome-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell types. Here, we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion model. In addition, we developed an approach to efficiently apply enzyme usage constraints in a comprehensive metabolic model of human cells. The combined modeling reproduced severe hypoxic conditions and the Warburg effect, and we found that limitations in enzymatic capacity contribute to cancer cells' preferential use of glutamine as a substrate to the citric acid cycle. Furthermore, we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites useful for the cancer cells. We identified over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated fibroblasts, but when limiting to metabolites previously identified to participate in such collaboration, no growth advantage was observed. Our work highlights the importance of enzymatic capacity limitations for cell behaviors and exemplifies the utility of enzyme-constrained models for accurate prediction of metabolism in cells and tumor microenvironments., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: A 3D printing grid-based method was developed to construct anthropomorphic phantoms with non-uniform activity distributions, to be used for evaluation of quantitative SPECT images. The aims were to characterize the grid-based method and to evaluate its capability to provide realistically shaped phantoms with non-uniform activity distributions., Methods: Characterization of the grid structures was performed by printing grid-filled spheres. Evaluation was performed by micro-CT imaging to investigate the printing accuracy and by studying the modulation contrast ([Formula: see text]) in SPECT images for 177 Lu and 99m Tc as a function of the grid fillable-volume fraction (FVF) determined from weighing. The grid-based technique was applied for the construction of two kidney phantoms and two thyroid phantoms, designed using templates from the XCAT digital phantoms. The kidneys were constructed with a hollow outer container shaped as cortex, an inner grid-based structure representing medulla and a solid section representing pelvis. The thyroids consisted of two lobes printed as grid-based structures, with void hot spots within the lobes. The phantoms were filled with solutions of 177 Lu (kidneys) or 99m Tc (thyroids) and imaged with SPECT. For verification, Monte Carlo simulations of SPECT imaging were performed for activity distributions corresponding to those of the printed phantoms. Measured and simulated SPECT images were compared qualitatively and quantitatively., Results: Micro-CT images showed that printing inaccuracies were mainly uniform across the grid. The relationships between the FVF from weighing and [Formula: see text] were found to be linear (r = 0.9995 and r = 0.9993 for 177 Lu and 99m Tc, respectively). The FVF-deviations from the design were up to 15% for thyroids and 4% for kidneys, mainly related to possibilities of cleaning after printing. Measured and simulated SPECT images of kidneys and thyroids exhibited similar activity distributions and quantitative comparisons agreed well, thus verifying the grid-based method., Conclusions: We find the grid-based technique useful for the provision of 3D printed, realistically shaped, phantoms with non-uniform activity distributions, which can be used for evaluation of different quantitative methods in SPECT imaging., (© 2024. The Author(s).)

Background: Persons with hearing loss (HL) are a vulnerable group in working life. Studies have shown that they are more likely than the general population to be in part-time work, to be unemployed, receive disability pension, and to be on sick leave. Many workers with HL also experience unhealthy work conditions, such as jobs where they experience high demands combined with low control as well as safety concerns and social isolation. There is a lack of studies that focus on factors that promote a healthy, sustainable work situation for the target group., Objective: To investigate health factors that contribute to a sustainable work situation for employees with HL., Methods: The current study was a comparative, observational study with a cross-sectional design including a clinical population of adults with HL. Comparisons were made between workers with HL "in work" and workers with HL on "HL-related sick leave"., Results: Seven health factors were identified. Those "in work" experienced a healthier work environment as well as lower levels of mental strain, hearing-related work characteristics and content, cognitively demanding work content, hearing-related symptoms, energy-demanding activities, and bodily aches and pain than those on "HL-related sick leave"., Conclusion: The results demonstrate a clear pattern regarding health factors for a sustainable working life. The type of job was not related to whether an individual was on sick leave or working. Rather, the work climate and the content of the work mattered.

Introduction: The activity meter is used to determine the activity of delivered radiopharmaceuticals, administered activity to patients and reference activity when gamma-cameras are calibrated prior to imaged-based dosimetry. The aim is to describe a procedure for cross-calibration of activity meters at different clinical sites, and report on 177 Lu activity results when using factory-set calibration factors compared to when calibration is performed with traceability to a primary standard., Methods: Thirty activity meters placed at seven hospitals in Norway and Sweden from four manufacturers: Capintec, Commecer, NuviaTech and Veenstra were included. A stock solution with 177 Lu was prepared at the local sites and measured in each activity meter with factory settings. The solution was shipped to the reference site at Lund University for measurements in a secondary standard activity meter. Deviations between local and reference activity measurements were determined for three geometries: 25-mL vial, 10-mL syringe and 1-mL syringe., Results: The median of the deviations was 6.4 % for the 25 mL vial, 5.9 % for the 10 mL syringe and 6.8 % for the 1 mL syringe. The median of the deviations for the 25 mL vial, was 1.5 % for activity meters from Capintec, 7.0 % for Comecer, 11.0 % for NuviaTech and 2.4 % for Veenstra. The majority of the deviations were positive and the maximum deviation was 14.5 %., Conclusion: The activity of 177 Lu measured in an activity meter with factory-set dial settings may yield deviations up to 14.5%, compared to activities measured with traceability to a primary standard. This would imply an undertreatment of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Molecular radiotherapy is rapidly expanding, and new radiotherapeutics are emerging. The majority of treatments is still performed using empirical fixed activities and not tailored for individual patients. Molecular radiotherapy dosimetry is often seen as a promising candidate that would allow personalisation of treatments as outcome should ultimately depend on the absorbed doses delivered and not the activities administered. The field of molecular radiotherapy dosimetry has made considerable progress towards the feasibility of routine clinical dosimetry with reasonably accurate absorbed-dose estimates for a range of molecular radiotherapy dosimetry applications. A range of challenges remain with respect to the accurate quantification, assessment of time-integrated activity and absorbed dose estimation. In this review, we summarise a range of technological and methodological advancements, mainly focussed on beta-emitting molecular radiotherapeutics, that aim to improve molecular radiotherapy dosimetry to achieve accurate, reproducible, and streamlined dosimetry. We describe how these new technologies can potentially improve the often time-consuming considered process of dosimetry and provide suggestions as to what further developments might be required., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Objectives: Self-assessment instruments are commonly used in audiological rehabilitation. However, several studies highlight the lack of multidimensionality in existing outcome measures, with the consequence that they only partially capture aspects of functioning in everyday life for people living with hearing loss. This study aimed to develop and investigate the content validity of a self-assessment instrument based on the validated Brief International Classification of Functioning, Disability, and Health Core Set for Hearing Loss., Design: The design was a two-part instrument development study. The first part focused on the item-generation process of the instrument, named the Hearing and Functioning in Everyday Life Questionnaire (HFEQ) during an experts' workshop. The second part focused on international content validation of the instrument using group interviews. Strategic sampling was used and 30 adults with hearing loss from India, South Africa, and the United States participated in the group interviews., Results: The expert's workshop resulted in the first version of the HFEQ containing 30 items. The results from group interviews show that the content of the HFEQ was considered to be valid concerning its relevance, comprehensiveness, and comprehensibility. A majority (73%) of the HFEQ items were perceived by the participants as relevant and easy to comprehend. For the remaining 27% of the items, the content was perceived to be relevant in all countries, but some terms and expressions were reported to require rewording or clearer examples. These modifications will be made in the next step of the development process., Conclusion: Content validation of the HFEQ demonstrates promising results, with participants perceiving the content as relevant and comprehensible. Further psychometric validation is required to investigate other psychometric properties, such as construct validity and reliability. The HFEQ has the potential to become a valuable new instrument for assessing everyday functioning in people with hearing loss in audiological rehabilitation and in research., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dosimetry in radionuclide therapy often requires the calculation of average absorbed doses within and between spatial regions, for example, for voxel-based dosimetry methods, for paired organs, or across multiple tumors. Formation of such averages can be made in different ways, starting from different definitions., Purpose: The aim of this study is to formally specify different averaging strategies for absorbed doses, and to compare their results when applied to absorbed dose distributions that are non-uniform within and between regions., Methods: For averaging within regions, two definitions of the average absorbed dose are considered: the simple average over the region (the region average) and the average when weighting by the mass density (density-weighted region average). The latter is shown to follow from the definition of mean absorbed dose according to the ICRU, and to be consistent with the MIRD formalism. For averaging between different spatial regions, three definitions follow: the volume-weighted, the mass-weighted, and the unweighted average. With respect to characterizing non-uniformity, the different average definitions lead to the use of dose-volume histograms (DVHs) (region average), dose-mass histograms (DMHs) (density-weighted region average), and unweighted histograms (unweighted average). Average absorbed doses are calculated for three worked examples, starting from the different definitions. The first, schematic, example concerns the calculation of the average absorbed dose between two regions with different volumes or mass densities. The second, stylized, example concerns voxel-based dosimetry, for which the average absorbed-dose rate within a region is calculated. The geometries studied include three 177 Lu-filled voxelized spheres, where the sphere masses are held constant while the material compositions, densities, and volumes are varied. For comparison, the mean absorbed-dose rates obtained using unit-density sphere S-values are also included. The third example concerns SPECT/CT-based tumor dosimetry for five patients undergoing therapy with 177 Lu-PSMA and six patients undergoing therapy with 177 Lu-DOTA-TATE, for which the average absorbed-dose rates across multiple tumors are calculated. For the second and third examples, analyses also include representations by histograms., Results: Example 1 shows that the average absorbed doses, calculated using different definitions, can differ considerably if the masses and absorbed doses for two regions are markedly different. From example 2 it is seen that the density-weighted region average is stable under different activity and density distributions and is also in line with results using S-values. In contrast, the region average varies as function of the activity distribution. In example 3, the absorbed dose rates for individual tumors differ by (1.1 ± 4.3)% and (-0.1 ± 0.4)% with maximum deviations of +34.4% and -1.4% for 177 Lu-PSMA and 177 Lu-DOTA-TATE, respectively, when calculated as region averages or density-weighted region averages, with largest deviations obtained when the density is non-uniform. The average absorbed doses calculated across all tumors are similar when comparing mass-weighted and volume-weighted averages but these differ substantially from unweighted averages., Conclusion: Different strategies for averaging of absorbed doses within and between regions can lead to substantially different absorbed-dose estimates. At reporting of radionuclide therapy dosimetry, it is important to specify the averaging strategy applied., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

One example of a PET exam that suffers from noise problems is [ 68 Ga]Ga-DOTA-TOC, where patients are generally administered between 100 and 200 MBq [ 68 Ga]Ga-DOTA-TOC, irrespective of size. However, a fixed activity can result in low signal-to-noise ratios (SNRs) in larger patients. This study aimed to evaluate the impact on image quality with respect to injected activity and patient habitus through Monte Carlo (MC) simulation. Eight anthropomorphic computer phantoms with body mass indices (BMIs) between 19 kg/m 2 and 38 kg/m 2 and tumours distributed in the liver were simulated using the MC software Gate v8.2 with an activity distribution defined according to [ 68 Ga]Ga-DOTA-TOC standardised uptake values. Three activity-administration protocols were simulated: (i) with a fixed activity of 100 MBq, (ii) with the activity scaled by 2 MBq/kg, and (iii) with the activity scaled by a body size-dependent power-function based on the SNR obtained with (ii). BMI, weight, body surface area, and abdominal circumference were evaluated body size parameters. Images were reconstructed with the CASToR software and evaluated for background SNR and lesion contrast-to-noise ratio (CNR). Large SNR variabilities were obtained with protocols (i) and (ii), while (iii) generated good consistency. Several tumours failed to reach a CNR of 5 for large phantoms with protocol (i), but the CNR was generally improved by (ii) and (iii). An activity scaled by patient habitus generate better image quality consistency, which increases the likelihood that patients receive a similar standard of care., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Research has indicated that the effectiveness of intervention programs is affected by how well these programs are implemented, but key gaps remain in our understanding of the factors that promote or inhibit implementation. This study examined how demographic characteristics and perceived work environment among early childhood educators were associated with implementation outcomes of the Increased Health and Wellbeing in Preschools (DAGIS) intervention, which was conducted as a cluster randomized trial., Methods: Participants included 101 educators from 32 intervention preschool classrooms. Data were analyzed at the classroom level, as the DAGIS intervention was delivered in preschool classrooms consisting of several educators instead of individual implementers. Linear regression was used to estimate the associations of educators' demographic characteristics and perceived work environment with different aspects of implementation (i.e., dose delivered; dose received - exposure; dose received - satisfaction; and perceived quality, as well as a total sum score based on these four dimensions). Municipality was controlled in the adjusted models., Results: Findings indicated that having a higher proportion of educators with a Bachelor's or Master's degree in education within the classroom was associated with higher dose received - exposure and higher total degree of implementation, and the significance of the models was unaffected by adjustment for municipality. Moreover, having a higher proportion of educators younger than 35 years within the classroom was associated with higher dose received - exposure. However, the association was non-significant when adjusted for municipality. No other educator factor (i.e., work experience in years and perceived support from coworkers, group work, and innovative climate) predicted implementation outcomes., Conclusions: Higher educational attainment and younger age among educators at the classroom level were associated with higher scores for some of the implementation outcomes. Educators' work experience in years at the current preschool and in early childhood education, support from coworkers, group work, and innovative climate were not significantly associated with any implementation outcomes. Future research should explore ways to improve educators' implementation of interventions aimed at promoting children's health behaviors., (© 2023. The Author(s).)

Objective. The aim was to theoretically and experimentally investigate recovery in SPECT images with objects of different shapes. Furthermore, the accuracy of volume estimation by thresholding was studied for those shapes. Approach. Nine spheres, nine oblate spheroids, and nine prolate spheroids phantom inserts were used, of which the six smaller spheres were part of the NEMA IEC body phantom and the rest of the inserts were 3D-printed. The inserts were filled with 99m Tc and 177 Lu. When filled with 99m Tc, SPECT images were acquired in a Siemens Symbia Intevo Bold gamma camera and when filled with 177 Lu in a General Electric NM/CT 870 DR gamma camera. The signal rate per activity (SRPA) was determined for all inserts and represented as a function of the volume-to-surface ratio and of the volume-equivalent radius using VOIs defined according to the sphere dimensions and VOIs defined using thresholding. Experimental values were compared with theoretical curves obtained analytically (spheres) or numerically (spheroids), starting from the convolution of a source distribution with a point-spread function. Validation of the activity estimation strategy was performed using four 3D-printed ellipsoids. Lastly, the threshold values necessary to determine the volume of each insert were obtained. Main results. Results showed that SRPA values for the oblate spheroids diverted from the other inserts, when SRPA were represented as a function of the volume-equivalent radius. However, SRPA values for all inserts followed a similar behaviour when represented as a function of the volume-to-surface ratio. Results for ellipsoids were in agreement with those results. For the three types of inserts the volume could be accurately estimated using a threshold method for volumes larger than 25 ml. Significance. Determination of SRPA independently of lesion or organ shape should decrease uncertainties in estimated activities and thereby, in the long term, be beneficial to patient care., (© 2023 Institute of Physics and Engineering in Medicine.)

Background: The COVID-19 pandemic has had implications for adolescents' interpersonal relationships, communication patterns, education, recreational activities and well-being. An understanding of the impact of the pandemic on their mental health is crucial in measures to promote the post-pandemic recovery. Using a person-centered approach, the current study aimed to identify mental health profiles in two cross-sectional samples of Finnish adolescents before and after the peak of the pandemic, and to examine how socio-demographic and psychosocial factors, academic expectations, health literacy, and self-rated health are associated with the emerging profiles., Methods and Findings: Survey data from the Health Behaviour in School-aged Children (HBSC) study conducted in Finland in 2018 (N = 3498, age M = 13.44) and 2022 (N = 3838, age M = 13.21) were analyzed. A four-profile model using cluster analysis was selected for both samples. In Sample 1, the identified profiles were (1) "Good mental health", (2) "Mixed psychosocial health", (3) "Somatically challenged", and (4) "Poor mental health". In Sample 2, the identified profiles were (1) "Good mental health", (2) "Mixed psychosomatic health", (3) "Poor mental health and low loneliness", and (4) "Poor mental health and high loneliness". The results of the mixed effect multinomial logistic regression analysis showed that in both samples, being a girl and reporting lower maternal monitoring; lower family, peer, and teacher support; higher intensity of online communication; a less positive home atmosphere and school climate; and poor self-rated health were most strongly linked to belonging to a poorer mental health profile. In addition, in Sample 2, low subjective health literacy was a key factor associated with poorer mental health profiles, and teacher support was more important than before COVID., Conclusions: The current study stresses the importance of identifying those vulnerable to developing poor mental health. To maximize post-pandemic recovery, the role of schools, especially teacher support and health literacy, along with the factors that remained important over time should be taken into account in public health and health promotion interventions., (© 2023. The Author(s).)

Single-cell RNA sequencing combined with genome-scale metabolic models (GEMs) has the potential to unravel the differences in metabolism across both cell types and cell states but requires new computational methods. Here, we present a method for generating cell-type-specific genome-scale models from clusters of single-cell RNA-Seq profiles. Specifically, we developed a method to estimate the minimum number of cells required to pool to obtain stable models, a bootstrapping strategy for estimating statistical inference, and a faster version of the task-driven integrative network inference for tissues algorithm for generating context-specific GEMs. In addition, we evaluated the effect of different RNA-Seq normalization methods on model topology and differences in models generated from single-cell and bulk RNA-Seq data. We applied our methods on data from mouse cortex neurons and cells from the tumor microenvironment of lung cancer and in both cases found that almost every cell subtype had a unique metabolic profile. In addition, our approach was able to detect cancer-associated metabolic differences between cancer cells and healthy cells, showcasing its utility. We also contextualized models from 202 single-cell clusters across 19 human organs using data from Human Protein Atlas and made these available in the web portal Metabolic Atlas, thereby providing a valuable resource to the scientific community. With the ever-increasing availability of single-cell RNA-Seq datasets and continuously improved GEMs, their combination holds promise to become an important approach in the study of human metabolism.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are formed by metabolism from the flame retardants polybrominated diphenyl ethers (PBDEs). In the aquatic environment, they are also produced naturally. OH-PBDEs are known for their potential to disrupt energy metabolism, the endocrine system, and the nervous system. This is the first study focusing on the effects of OH-PBDEs at the metabolite level in vivo. The aim of the current study was to investigate the metabolic effects of exposure to OH-PBDEs using metabolomics, and to identify potential biomarker(s) for energy disruption of OH-PBDEs. Zebrafish (Danio rerio) embryos were exposed to two different concentrations of 6-OH-BDE47 and 6-OH-BDE85 and a mixture of these two compounds. In total, 342 metabolites were annotated and 79 metabolites were affected in at least one exposure. Several affected metabolites, e.g. succinic acid, glutamic acid, glutamine, tyrosine, tryptophan, adenine, and several fatty acids, could be connected to known toxic mechanisms of OH-PBDEs. Several phospholipids were strongly up-regulated with up to a six-fold increase after exposure to 6-OH-BDE47, a scarcely described effect of OH-PBDEs. Based on the observed metabolic effects, a possible connection between disruption of the energy metabolism, neurotoxicity and potential immunotoxicity of OH-PBDEs was suggested. Single compound exposures to 6-OH-BDE47 and 6-OH-BDE85 showed little overlap in the affected metabolites. This shows that compounds of similar chemical structure can induce different metabolic effects, possibly relating to their different toxic mechanisms. There were inter-concentration differences in the metabolic profiles, indicating that the metabolic effects were concentration dependent. After exposure to the mixture of 6-OH-BDE47 and 6-OH-BDE85, a new metabolic profile distinct from the profiles obtained from the single compounds was observed. Succinic acid was up-regulated at the highest, but still environmentally relevant, concentration of 6-OH-BDE47, 6-OH-BDE85, and the mixture. Therefore, succinic acid is suggested as a potential biomarker for energy disruption of OH-PBDEs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Supported Employment (SE) has shown better results in the employment rate for persons with disabilities than other methods within vocational rehabilitation, but how SE affects the employment rate for subgroups in the interventions needs further attention., Objective: To examine previous research regarding the influence of intersecting statuses on the employment rate in SE for people with psychiatric, neuropsychiatric, or intellectual disabilities according to type of diagnosis, sex, race/ethnicity, age, level of education and previous work history., Methods: A systematic literature search was conducted in nine databases including peer-reviewed articles from 2000 to April 2021. Articles presenting the employment rate in SE interventions according to the intersecting statuses listed in the objective were included., Results: The searches identified 3777 unique records, of which 53 articles were included in data extraction. In most of the included articles, intersecting statuses did not affect the employment rate for people in the SE interventions with psychiatric disabilities. Few studies have examined neuropsychiatric and intellectual disabilities. A majority of the studies subjected to full-text analysis were excluded due to a lack of reporting of the effects of intersecting statuses on the employment rate. The studies that reported on the effects of intersecting statuses on the employment rate often had small samples and lacked statistical power., Conclusions: Intersecting statuses do not appear to affect the employment rate for people receiving SE interventions, but systematic reviews with pooled samples need to be undertaken because of the low reporting rate and underpowered sample sizes in existing studies.

Background: Somatostatin receptor 68 Ga PET imaging is standard for evaluation of a patient's suitability for 177 Lu peptide receptor radionuclide therapy of neuroendocrine tumours (NETs). The 68 Ga PET serves to ensure sufficient somatostatin receptor expression, commonly evaluated qualitatively. The aim of this study is to investigate the quantitative relationships between uptake in 68 Ga PET and absorbed doses in 177 Lu therapy., Method: Eighteen patients underwent [ 68 Ga]Ga-DOTA-TATE PET imaging within 20 weeks prior to their first cycle of [ 177 Lu]Lu-DOTA-TATE. Absorbed doses for therapy were estimated for tumours, kidney, spleen, and normal liver parenchyma using a hybrid SPECT/CT-planar method. Gallium-68 activity concentrations were retrieved from PET images and also used to calculate SUVs and normalized SUVs, using blood and tissue for normalization. The 68 Ga activity concentrations per injected activity, SUVs, and normalized SUVs were compared with 177 Lu activity concentrations 1 d post-injection and 177 Lu absorbed doses. For tumours, for which there was a variable number per patient, both inter- and intra-patient correlations were analysed. Furthermore, the prediction of 177 Lu tumour absorbed doses based on a combination of tumour-specific 68 Ga activity concentrations and group-based estimates of the effective half-lives for grade 1 and 2 NETs was explored., Results: For normal organs, only spleen showed a significant correlation between the 68 Ga activity concentration and 177 Lu absorbed dose (r = 0.6). For tumours, significant, but moderate, correlations were obtained, with respect to both inter-patient (r = 0.7) and intra-patient (r = 0.45) analyses. The correlations to absorbed doses did not improve when using 68 Ga SUVs or normalized SUVs. The relationship between activity uptakes for 68 Ga PET and 177 Lu SPECT was stronger, with correlation coefficients r = 0.8 for both inter- and intra-patient analyses. The 177 Lu absorbed dose to tumour could be predicted from the 68 Ga activity concentrations with a 95% coverage interval of - 65% to 248%., Conclusions: On a group level, a high uptake of [ 68 Ga]Ga-DOTA-TATE is associated with high absorbed doses at 177 Lu-DOTA-TATE therapy, but the relationship has a limited potential with respect to individual absorbed dose planning. Using SUV or SUV normalized to reference tissues do not improve correlations compared with using activity concentration per injected activity., (© 2022. The Author(s).)

To date, the energy-intensive production and high-water content severely limits nanocellulose applications on a large scale off-site. In this study, adding water-soluble polysaccharides (PS) to achieve an integrated process of water-redispersible nanocellulose production was well established. The addition of PS, in particular carboxymethylated-galactoglucomannan (cm-GGM), facilitates fibre fibrillation enabling homogenization at a higher solid content at 1.5 wt% compared with around 0.4 wt% for neat fibre. More importantly, the addition of cm-GGM saved 73 % energy in comparison without PS addition. Good water redispersibility of thus-prepared nanocellulose was validated in viewpoints of size distribution, morphology, viscosity and film properties as compared with neat nanocellulose. The tensile strength and optical transmittance of nanocellulose films increased to 116 MPa and 77 % compared to those without PS addition of 62 MPa and 74 %, respectively. Collectively, this study provides a new avenue for large-volume production of redispersible nanocellulose at a high solid content with less energy-consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Reliable forecast of COVID-19 hospital admissions in near-term horizons can help enable effective resource management which is vital in reducing pressure from healthcare services. The use of mobile network data has come to attention in response to COVID-19 pandemic leveraged on their ability in capturing people social behavior. Crucially, we show that there are latent features in irreversibly anonymized and aggregated mobile network data that carry useful information in relation to the spread of SARS-CoV-2 virus. We describe development of the forecast models using such features for prediction of COVID-19 hospital admissions in near-term horizons (21 days). In a case study, we verified the approach for two hospitals in Sweden, Sahlgrenska University Hospital and Södra Älvsborgs Hospital, working closely with the experts engaged in the hospital resource planning. Importantly, the results of the forecast models were used in year 2021 by logisticians at the hospitals as one of the main inputs for their decisions regarding resource management., (© 2022. The Author(s).)

Background: Digital transformation has influenced all areas of adolescents' lives, including the ways adolescents maintain friendships. Interpersonal communication is one of the most common activities while online. Online communication may provide adolescents with opportunities to expand their social contacts, but these encounters can be risky, especially when the communication is with unknown people on the internet. This study examined the associations between different forms of online communication behavior and well-being., Materials and Methods: Data were collected from Finnish adolescents as part of the Health Behavior in School-Aged Children (HBSC) study in 2018. The participants were 3,140 Finnish adolescents aged 11-15 years. Descriptive analyses were used to examine the frequency of different forms of online communication behaviors. The associations between online communications and individual factors were analyzed using the X 2 test and 95% confidence intervals. Structural equation modeling (SEM) was used to analyze the extent to which adolescents' online communication behavior explained the variance in adolescents' well-being indicators., Results: Overall, 60% of the adolescents reported communicating intensively with close friends, with higher rates of intensive communication reported by girls, higher age groups, and the high health literacy group. 22% of adolescents reported intensive communication with friends they got to know through the internet (online friends), while intensive online communication with unknown people was reported by 13% of adolescents. Overall, around one-fourth of adolescents preferred sharing personal matters online rather than in face-to-face encounters, and 10% of adolescents reported using the internet daily to get to know new people, and to look for like-minded company. The SEM analysis showed that keeping online contact with offline friends was linked to a positive outcome in all the measured well-being indicators; however, intensive communication with people contacted only online (online friends and unknown people) was negatively associated with well-being indicators (lower self-rated health, lower life satisfaction, higher loneliness, and problematic social media use)., Conclusion: Both positive and negative associations were observed between online communication and well-being, depending on the target and content of the communication. The results indicate that online communication has benefits for adolescents who have more offline social life. Overall, one should ensure that the impact of interventions is proportionately greater for adolescents at the bottom end of the health gradient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lyyra, Junttila, Gustafsson, Lahti and Paakkari.)

This study aimed to investigate how maternal birthweight is related to early pregnancy obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Females born term and singleton in Sweden between 1973 and 1995 (N = 305,893) were studied at their first pregnancy. Information regarding their birthweight, early pregnancy body mass index, and pregnancy complications was retrieved from the Swedish Medical Birth Register, as were data on their mothers and offspring. High maternal birthweights (2-3 standard deviation scores (SDS) and >3 SDS) were associated with greater odds of early pregnancy obesity, odds ratio (OR) 1.52 (95% confidence interval (CI) 1.42-1.63) and OR 2.06 (CI 1.71-2.49), respectively. A low maternal birthweight (<2 SDS) was associated with greater odds of GDM (OR 2.49, CI 2.00-3.12). No association was found between high maternal birthweight and GDM. A maternal birthweight 2-3 SDS was associated with offspring birthweight 2-3 SDS (OR 3.83, CI 3.44-4.26), and >3 SDS (OR 3.55, CI 2.54-4.97). Corresponding ORs for a maternal birthweight >3 SDS were 5.38 (CI 4.12-7.01) and 6.98 (CI 3.57-13.65), respectively. In conclusion, a high maternal birthweight was positively associated with early pregnancy obesity and offspring macrosomia. A low, but not a high maternal birthweight, was associated with GDM.

Background: In recent years, a lot of effort has been put in the enhancement of medical imaging using artificial intelligence. However, limited patient data in combination with the unavailability of a ground truth often pose a challenge to a systematic validation of such methodologies. The goal of this work was to investigate a recently proposed method for an artificial intelligence-based generation of synthetic SPECT projections, for acceleration of the image acquisition process based on a large dataset of realistic SPECT simulations., Methods: A database of 10,000 SPECT projection datasets of heterogeneous activity distributions of randomly placed random shapes was simulated for a clinical SPECT/CT system using the SIMIND Monte Carlo program. Synthetic projections at fixed angular increments from a set of input projections at evenly distributed angles were generated by different u-shaped convolutional neural networks (u-nets). These u-nets differed in noise realization used for the training data, number of input projections, projection angle increment, and number of training/validation datasets. Synthetic projections were generated for 500 test projection datasets for each u-net, and a quantitative analysis was performed using statistical hypothesis tests based on structural similarity index measure and normalized root-mean-squared error. Additional simulations with varying detector orbits were performed on a subset of the dataset to study the effect of the detector orbit on the performance of the methodology. For verification of the results, the u-nets were applied to Jaszczak and NEMA physical phantom data obtained on a clinical SPECT/CT system., Results: No statistically significant differences were observed between u-nets trained with different noise realizations. In contrast, a statistically significant deterioration was found for training with a small subset (400 datasets) of the 10,000 simulated projection datasets in comparison with using a large subset (9500 datasets) for training. A good agreement between synthetic (i.e., u-net generated) and simulated projections before adding noise demonstrates a denoising effect. Finally, the physical phantom measurements show that our findings also apply for projections measured on a clinical SPECT/CT system., Conclusion: Our study shows the large potential of u-nets for accelerating SPECT/CT imaging. In addition, our analysis numerically reveals a denoising effect when generating synthetic projections with a u-net. Clinically interesting, the methodology has proven robust against camera orbit deviations in a clinically realistic range. Lastly, we found that a small number of training samples (e.g., ~ 400 datasets) may not be sufficient for reliable generalization of the u-net., (© 2022. The Author(s).)