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Background: Active Support is a staff practice that aims to increase engagement of people with intellectual disabilities. This study seeks to: (1) identify the outcomes of staff using Active Support and how these are measured; (2) identify how the views of people with intellectual disabilities have been included in Active Support research. Method: A scoping review was conducted of peer‐reviewed articles about Active Support published between 2009 and 2023. Results: Sixteen articles were identified. Outcomes included engagement, the quality of staff support, choice and challenging behaviour. Structured observations were the most frequently used measurement method. Only two studies explored people with intellectual disabilities' perspectives about Active Support. Conclusions: Consistent use of similar measures is a strength of Active Support research. Including perspectives of people with intellectual disabilities may provide insight into dimensions of support not been measured and assist in further developing these measures and Active Support practice. [ABSTRACT FROM AUTHOR]

Deep eutectic solvents (DESs) have garnered attention in Li‐ion battery (LIB) recycling due to their declared eco‐friendly attributes and adjustable metal dissolution selectivity, offering a promising avenue for recycling processes. However, DESs currently lack competitiveness compared to mineral acids, commonly used in industrial‐scale LIB recycling. Current research primarily focuses on optimizing DES formulation and experimental conditions to maximize metal dissolution yields in standalone leaching experiments. While achieving yields comparable to traditional leaching systems is important, extensive DES reuse is vital for overall recycling feasibility. To achieve this, evaluating the metal dissolution mechanism can assist in estimating DES consumption rates and assessing process makeup stream costs. The selection of appropriate metal recovery and DES regeneration strategies is essential to enable subsequent reuse over multiple cycles. Finally, decomposition of DES components should be avoided throughout the designed recycling process, as by‐products can impact leaching efficiency and compromise the safety and environmental friendliness of DES. In this review, these aspects are emphasized with the aim of directing research efforts away from simply pursuing the maximization of metal dissolution efficiency, towards a broader view focusing on the application of DES beyond the laboratory scale. [ABSTRACT FROM AUTHOR]

Digital Humanities has an increasing need for widely applicable and easy-to-use methods across disciplinary boundaries. We believe that the cross-disciplinary methods we have developed for the study of the ancient Near East are useful for the study of other research questions outside the field of "Digital Assyriology". The article presents an overview of automated language processing for lexical-semantic analysis, social network analysis, and content analysis. We draw on the work in our research group, which aims to address how changing empires affect social group identities and lifeways in the first millennium BCE in Mesopotamia. The article places the methods our research team has developed into the larger methodological context of Digital Humanities (DH). The article presents an overview of the tools our research group has found useful in our study of ancient social groups. Sections 1 and 2 give the necessary background for the reader to understand the particular challenges related to the study of ancient Mesopotamia and how we have overcome them. The concrete case studies presented in Sections 3 and 4, however, are kept as general as possible, to facilitate similar approaches in adjacent fields of study. Our methodology and approaches are well documented and openly available, and in our view can be used on similar text materials, by other groups interested in DH approaches. [ABSTRACT FROM AUTHOR]

Purpose: Return-to-work coordinators (RTWCs) give people on sick leave individualized support and coordinate between different stakeholders, including physicians. The aim of this study was to explore physicians' experience of RTWCs and investigate factors that influence how much physicians collaborate with RTWCs, or refer patients to them, in primary, orthopaedic, and psychiatric care clinics. Materials and methods: Of the 1229 physicians responding to a questionnaire, 629 physicians who had access to a RTWC in their clinic answered to questions about collaborating with RTWCs. Results: Among physicians who had access to a RTWC, 29.0% collaborated with a RTWC at least once a week. Physicians with a more favourable experience of RTWCs reported more frequent collaboration (adjusted OR 2.92, 95% CI 2.06–4.15). Physicians also collaborated more often with RTWCs if they reported to often deal with problematic sick-leave cases, patients with multiple diagnoses affecting work ability, and conflicts with patients over sickness certification. Conclusions: Physicians who had more problematic sick-leave cases to handle and a favourable experience of RTWCs, also reported collaborating more often with RTWCs. The results indicate that RTWCs' facilitation of contacts with RTW stakeholders and improvements in the sickness certification process may be of importance for physicians. IMPLICATIONS FOR REHABILITATION: This study of physicians' experience of collaborating with return-to-work coordinators (RTWCs) observes that physicians reported more collaboration with or referrals to coordinators if they had a favourable experience of coordinators. The results indicate that physicians report more collaboration with or referrals to RTWCs if they had more problematic sick-leave cases to handle in the clinic. These findings imply that it might be possible to increase the collaboration between physicians and RTWCs in clinical settings by managing factors of importance. [ABSTRACT FROM AUTHOR]

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The nickel metal hydride (NiMH) battery technology has been designed for use in electric vehicles, solar-powered applications and power tools. These batteries contain the critical and strategic raw materials cobalt, nickel and several rare earth elements (REE). When designing a battery recycling process, there are several choices to be made regarding end-products and process chemicals. The aim of this study is to investigate and compare the environmental and economic sustainability of different recycling options for NiMH batteries by taking projected market developments into consideration and by applying life cycle assessment and life cycle costing methods. The comparative study is limited to recovery of the REEs. Two hydrometallurgical processes for recovery of the REEs from the anode material are compared with extraction of REEs from primary sources in China. The processes compared are a high-temperature sulfation roasting process and a process based on hydrochloric acid leaching followed by precipitation of REE oxalates. By comparing the different recycling approaches, the hydrochloric acid process performs best. However, the use of oxalic acid has a large impact on the overall sustainability footprint. For the sulfation roasting process, the energy, sodium hydroxide and sulphuric acid consumption contribute most to the total environmental footprint. This article is part of the discussion meeting issue 'Sustainable metals: science and systems'. [ABSTRACT FROM AUTHOR]

Background: Our population‐based study has previously shown that being born in winter or spring was associated with adult‐onset asthma. The aim was to study if season of birth (SOB) is associated with airway allergy and related diseases: NSAID exacerbated respiratory disease (N‐ERD), asthma, allergic rhinitis (AR), nonallergic rhinitis (NAR), chronic rhinosinusitis with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) in Finland. Methods: A randomly sampled retrospective registry‐based follow‐up data (n = 74,868) of patients visiting Hospital District of Helsinki and Uusimaa (HUS) in Finland was used. The birth date, sex, visit date and comorbidities were collected from electronic health record data during visits from 2005 to 2019. Results: The mean (SD, range) age of the sample was 34.53 (25.47, 0–102) years, with 48.7 % being men. We divided the whole population in four groups based on the season they were born (SOB‐groups). When observing these four SOB‐groups, the proportion of those having asthma was 43.1%, 42.1%, 41.1%, 42.7%, in winter, spring, summer, and autumn SOB‐groups, respectively. The proportion of those having AR was 12.6%, 12.0%, 10.7%, 12.1%, respectively. When having summer as a reference, being born in any other time of year was significantly associated with AR and, being born in autumn or winter was associated with asthma. No significant association was observed in CRS or N‐ERD or NAR groups in adjusted models. Conclusions: The study suggests that early life immunological events may have a role a role in pathogenesis of asthma and AR. As no association was observed between SOB and CRSsNP, CRSwNP, N‐ERD or NAR, further studies on this are warranted. [ABSTRACT FROM AUTHOR]

Authenticity in schools has been highlighted as important for improving students' engagement and learning, and to prepare them for future job markets, especially in science and technology. This study investigates students' perceived authenticity of a developed innovation project when implemented in an upper secondary technology education program. Three cohorts of students (n = 199) attended a first-year technology course at a Swedish upper secondary school in 2016, 2017 and 2018, respectively. In addition, eleven students from the 2016 cohort were interviewed two years later to obtain their views on how the innovation project in the first-year course influenced their performance in a subsequent advanced technology course taken in 2017–2018. Groups of students participated in the first phase of an innovation project in the first-year course, a five-week module, cooperatively designing solutions to real-world problems. A Likert scale questionnaire measured the degree of perceived authenticity in line with Herrington, Reeves and Oliver's (2010) key elements. Focus group interviews were conducted after the second phase – a 20-week follow-up module in the subsequent advanced course – about how authentic they perceived the first and second phases to be. A questionnaire measured the degree of perceived authenticity of the students for the first phase, for each of the three years. Coaching and scaffolding received the highest ratings across all three years, whereas Reflection was perceived as having the lowest authenticity. In a qualitative component of the study students found both phases positive, and five new themes of students' perception of their experiences were revealed. The similarities in perceived authenticity between the three cohorts suggest consistency in students' perceptions of authenticity. However, they did not feel that the project gave them the opportunity to reflect on their learning. According to interviews conducted two years later, they perceived their experiences of the innovation project as having induced creativity, commitment, ownership, motivation, and real-world connection, although at times it was also a challenge to think for themselves and to collaborate with others. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) in human milk may have important functions in lactation and infant health. This longitudinal pilot cohort study investigated the total nitrite and nitrate (NOx) concentration in human milk and maternal saliva during the first 60 days postpartum. Additionally, we explored the association between selected breastfeeding variables and milk and saliva NOx concentration. Human milk and maternal saliva samples were collected on days 2, 5, 14, 30, and 60 postpartum and analyzed for NOx concentration. Breastfeeding data were collected through self-assessed questions. Data analyses were performed using mixed models. The concentration of NOx in milk was significantly higher during the first 30 days compared to day 60, and there was a positive association between milk and saliva NOx concentrations throughout the entire study period. In absolute numbers, partially breastfeeding mothers had a lower concentration of NOx in milk on day 2 compared to exclusively breastfeeding mothers (8 vs. 15.1 μM, respectively). Partially breastfeeding mothers reported a later start of secretory activation and fewer mothers in this group started breastfeeding within the first hour after birth. Due to the small numbers, these differences could not be statistically evaluated. Further research is warranted to elucidate the role of NO in lactation success and breastfeeding outcomes. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic led to vast changes in working life and conditions in which we work. These changes may affect people with multiple sclerosis (PwMS) differently. We aimed to describe the working situation of PwMS during the COVID-19 pandemic and the pandemic's impact on their working lives. Methods: All individuals aged 20–50 listed in the Swedish Multiple Sclerosis Registry were invited to participate in an online survey in 2021. Closed and open-ended responses linked to individual-level register data were used in this exploratory mixed-methods study. Differences in the proportions reporting specific impacts were assessed with chi-square tests by sex, MS severity, education, and profession. The open-ended answers were analysed through content analysis. Results: Over 8500 PwMS were invited (52% response rate). We included the 3887 respondents who answered questions about the impact of the pandemic on working life. Most (93.7%) reported being in paid work. An impact of the ongoing pandemic to one's daily occupation was reported by 26.2%, with different characteristics observed across the impacts. Four categories of type of answers were identified from the open-ended answers: Direct impact on one's occupation, Disclosing or concealing MS in the workplace, Worry and uncertainty, and Broader impact to life situation. Conclusions: PwMS navigated the pandemic by interrupting as well as continuing their working lives. Many PwMS reported that the pandemic did not affect their work situation. However, the reported impacts differed among the participants and a sense of uncertainty and worry was often underlying their statements. Lessons from the pandemic may support future work participation. [ABSTRACT FROM AUTHOR]

The presence of periodontal pathogens is associated with an increased prevalence of rheumatoid arthritis (RA). The systemic antibody response to epitopes of these bacteria is often used as a proxy to study correlations between bacteria and RA. The primary aim of the present study is to examine the correlation between the presence of Aggregatibacter actinomycetemcomitans (Aa) in the oral cavity and serum antibodies against the leukotoxin (LtxA) produced by this bacterium. The salivary presence of Aa was analyzed with quantitative PCR and serum LtxA ab in a cell culture-based neutralization assay. The analyses were performed on samples from a well-characterized RA cohort (n = 189) and a reference population of blood donors (n = 101). Salivary Aa was present in 15% of the RA patients and 6% of the blood donors. LtxA ab were detected in 19% of RA-sera and in 16% of sera from blood donors. The correlation between salivary Aa and serum LtxA ab was surprisingly low (rho = 0.55 [95% CI: 0.40, 0.68]). The presence of salivary Aa showed no significant association with any of the RA-associated parameters documented in the cohort. A limitation of the present study is the relatively low number of individuals with detectable concentrations of Aa in saliva. Moreover, in the comparison of detectable Aa prevalence between RA patients and blood donors, we assumed that the two groups were equivalent in other Aa prognostic factors. These limitations must be taken into consideration when the result from the study is interpreted. We conclude that a systemic immune response to Aa LtxA does not fully reflect the prevalence of Aa in saliva. In addition, the association between RA-associated parameters and the presence of Aa was negligible in the present RA cohort. [ABSTRACT FROM AUTHOR]

The early stages of the molecular self‐assembly pathway leading to crystal nucleation have a significant influence on the properties and purity of organic materials. This mini review collates the work on organic mesoscale clusters and discusses their importance in nucleation processes, with a particular focus on their critical properties and susceptibility to sample treatment parameters. This is accomplished by a review of detection methods, including dynamic light scattering, nanoparticle tracking analysis, small angle X‐ray scattering, and transmission electron microscopy. Considering the challenges associated with crystallisation of flexible and large‐molecule active pharmaceutical ingredients, the dynamic nature of mesoscale clusters has the potential to expand the discovery of novel crystal forms. By collating literature on mesoscale clusters for organic molecules, a more comprehensive understanding of their role in nucleation will evolve and can guide further research efforts. [ABSTRACT FROM AUTHOR]

The early stages of the molecular self‐assembly pathway leading to crystal nucleation have a significant influence on the properties and purity of organic materials. This mini review collates the work on organic mesoscale clusters and discusses their importance in nucleation processes, with a particular focus on their critical properties and susceptibility to sample treatment parameters. This is accomplished by a review of detection methods, including dynamic light scattering, nanoparticle tracking analysis, small angle X‐ray scattering, and transmission electron microscopy. Considering the challenges associated with crystallisation of flexible and large‐molecule active pharmaceutical ingredients, the dynamic nature of mesoscale clusters has the potential to expand the discovery of novel crystal forms. By collating literature on mesoscale clusters for organic molecules, a more comprehensive understanding of their role in nucleation will evolve and can guide further research efforts. [ABSTRACT FROM AUTHOR]

Anthelmintic resistance in equine parasite Parascaris univalens, compromises ivermectin (IVM) effectiveness and necessitates an in-depth understanding of its resistance mechanisms. Most research, primarily focused on holistic gene expression analyses, may overlook vital tissue-specific responses and often limit the scope of novel genes. This study leveraged gene co-expression network analysis to elucidate tissue-specific transcriptional responses and to identify core genes implicated in the IVM response in P. univalens. Adult worms (n = 28) were exposed to 10−11 M and 10−9 M IVM in vitro for 24 hours. RNA-sequencing examined transcriptional changes in the anterior end and intestine. Differential expression analysis revealed pronounced tissue differences, with the intestine exhibiting substantially more IVM-induced transcriptional activity. Gene co-expression network analysis identified seven modules significantly associated with the response to IVM. Within these, 219 core genes were detected, largely expressed in the intestinal tissue and spanning diverse biological processes with unspecific patterns. After 10−11 M IVM, intestinal tissue core genes showed transcriptional suppression, cell cycle inhibition, and ribosomal alterations. Interestingly, genes PgR028_g047 (sorb-1), PgB01_g200 (gmap-1) and PgR046_g017 (col-37 & col-102) switched from downregulation at 10−11 M to upregulation at 10−9 M IVM. The 10−9 M concentration induced expression of cuticle and membrane integrity core genes in the intestinal tissue. No clear core gene patterns were visible in the anterior end after 10−11 M IVM. However, after 10−9 M IVM, the anterior end mostly displayed downregulation, indicating disrupted transcriptional regulation. One interesting finding was the non-modular calcium-signaling gene, PgR047_g066 (gegf-1), which uniquely connected 71 genes across four modules. These genes were enriched for transmembrane signaling activity, suggesting that PgR047_g066 (gegf-1) could have a key signaling role. By unveiling tissue-specific expression patterns and highlighting biological processes through unbiased core gene detection, this study reveals intricate IVM responses in P. univalens. These findings suggest alternative drug uptake of IVM and can guide functional validations to further IVM resistance mechanism understanding. [ABSTRACT FROM AUTHOR]

Making service provisioning significantly more sustainable is crucial if humankind wants to make a serious effort to operate within the boundaries of what the planet can support. The purpose of this paper is to develop a systemic understanding of sustainability in service provision and shed light on the mechanisms that drive unsustainability and hinder service providers in their efforts to be more sustainable. To contextualize our study, we focus on a significant sustainability problem: food waste stemming from food retail at the retailer-consumer interface. We make two theoretical contributions to the service research on sustainability. First, we offer a systemic conceptualization of sustainability in service as a dynamic ability of a focal system (e.g., a service firm) to sustain the system(s) that contains it. Second, we explicate the mechanisms—stocks and flows, feedback and mindsets—that contribute to (un)sustainable service provision as a systemic behavior, and which can thus be used as intervention points when designing sustainability initiatives. Our work also has significant practical implications for food retailers and policymakers working towards reaching UN's Sustainable Development Goal 12.3, as we specify the feedback loops that drive food waste and hinder efforts to reduce it at the retailer-consumer interface. [ABSTRACT FROM AUTHOR]

In Sweden, allergy immunotherapy (AIT) is available as either subcutaneous immunotherapy (SCIT) injections or sublingual immunotherapy (SLIT) tablets and is used to treat moderate-severe allergic rhinitis (AR). This study sought to determine treatment-related CO2 emissions and travel times in Swedish patients receiving either SCIT or SLIT-tablets. A list of specialized Swedish AR clinics that administer AIT was determined, and respective co-ordinates retrieved. Swedish municipality population data were obtained from a national database. The mean distance from each Swedish municipality to the nearest AR clinic was calculated, adjusted using a detour index, and weighted by estimated patient population size. Transport modality data were obtained from a Swedish urban transport study and CO2 emissions were obtained from Government sources. The mean number of annual SLIT-tablets and SCIT doses required were calculated based on product labels and clinical expert input. The annual number of healthcare professional interactions were layered into the model to estimate changes in mean patient travel time, distance, and travel-related CO2 emissions associated with using SCIT versus SLIT-tablets. Mean annual travel-related CO2 emissions were 410 tonnes (to two significant figures [s.f.]; standard deviation [SD] 90) with SLIT-tablets, versus 1700 tonnes (SD 380) for SCIT, resulting in mean annual savings of approximately 1300 tonnes (SD 290) of CO2 if all AIT patients were to receive SLIT-tablets instead of SCIT, over 380 times greater than 2021 average Swedish CO2 emissions per capita. Approximate mean annual travel times for patients taking SLIT-tablets were 66,500 h (three s.f.; SD 14,400), and 278,000 h (SD 60,200) for SCIT, resulting in mean annual savings of 211,000 h (SD 45,800) if all AIT patients were to receive SLIT-tablets instead of SCIT. Compared with SCIT injections, SLIT-tablets led to substantial reductions in treatment-related CO2 emissions and travel times for Swedish patients. [ABSTRACT FROM AUTHOR]

Introduction: Overweight/obesity and strenuous working conditions are associated with work disability, but their joint contributions to sickness absence (SA) are unknown. We aimed to examine their joint contributions to SA periods of 1–7 and ≥8 days. Methods: Self-reported data on body mass index and working conditions, including perceived physically and mentally strenuous work and hours per day spent in heavy physical work, were linked to the employer's SA register for the City of Helsinki, Finland, employees (n = 4,323, women 78%) who were 19–39 years old at baseline. We calculated rate ratios (RRs) and 95% confidence intervals (CIs) for SA periods using negative binomial regression models among participants with healthy weight and overweight/obesity, with and without exposure to strenuous working conditions. The mean follow-up time was 2.1 years. Results: Participants with overweight/obesity and exposure to physically strenuous working conditions had the highest age- and gender-adjusted RRs for SA periods of both 1–7 and ≥8 days (physically strenuous work: RR: 1.38, CI: 1.25–1.52, and RR: 1.87, CI: 1.60–2.18, respectively; ≥3 h per day spent in physical work: RR: 1.40, CI: 1.26–1.55 and 2.04, CI: 1.73–2.40, respectively). The interaction between overweight/obesity and physically strenuous working conditions was additive for SA periods of 1–7 days and weakly synergistic for SA periods of ≥8 days. For mentally strenuous work, participants with overweight/obesity and exposure to mentally strenuous work had the highest age-adjusted RRs for SA periods of ≥8 days, and the interaction was additive. Conclusion: The joint contributions of overweight/obesity and exposure to strenuous working conditions to SA should be considered when aiming to reduce employees' SA. Employers might benefit from providing employees adequate support for weight management and adherence to healthy lifestyles while improving employees' working conditions. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a common disease in dogs, and daily dental home care in the form of tooth brushing is essential for prevention and treatment. Despite this, many studies reveal low adherence to tooth brushing advice. This study aimed to assess compliance with dental home care among dogs with periodontitis and understand the factors influencing brushing routines. A questionnaire survey was emailed to 63 dog owners whose dogs had been diagnosed with periodontitis, received dental cleaning at the University Animal Hospital, Swedish University of Agricultural Sciences and were given tooth brushing instructions. The survey was supplemented by telephone interviews, resulting in a 57% response rate. Results: The study presents dog owners' routines, experiences, attitudes, and motivation regarding tooth brushing. Approximately 42% brushed their dogs' teeth daily while others did so less frequently or not at all. Reported challenges, such as uncooperative dogs and difficulty establishing a routine, may explain infrequent brushing. Conclusions: While the study suggests that owners of dogs with periodontitis tend to follow dental care recommendations better than the general dog owner population, it also reveals that preventive care is inadequate for more than half of the dogs. Given the high prevalence of periodontitis, there's a need for resources to address infrequent tooth brushing. Understanding dog owners' needs can help establish daily brushing as a routine, improving canine oral health and overall well-being. [ABSTRACT FROM AUTHOR]

Inhomogeneous lignin from a canola (rapeseed) straw was isolated and valorized as regularly shaped spherical microparticles for drug delivery formulations. Lignin with a purity of 83% and broad molecular weight distribution (Ð > 5.0) was extracted by alkali pulping and acetylated to increase spheronization ability. Lignins with high degrees of acetylation (0.76 and 0.89) were successfully assembled into microparticles with uniform sizes (approximately 2 μm) and smooth spherical surfaces via solvent–antisolvent precipitation. Hydrophobic coumarin 153 and positively charged ciprofloxacin were used as model drugs to assess the encapsulation and release performance of lignin microparticles. Highly acetylated lignin microparticles displayed encapsulation efficiencies of 89.6% for coumarin 153% and 90.6% for ciprofloxacin. Scanning electron microscope images showed that coumarin 153 was encapsulated in the hydrophobic core, while ciprofloxacin was adsorbed on the less hydrophobic shell. The synthesis of lignin microcarriers not only provides a facile approach to utilizing waste canola straw lignin for drug delivery matrices but also has the potential to serve as an alternative lignin powder feedstock for bio-based materials. [ABSTRACT FROM AUTHOR]

Purpose: Second primary cancers (SPCs) after nasopharyngeal cancer (NPC) are rare, but have an impact on the follow-up of this patient population. The aim of this study is to systematically review the literature to determine the prevalence and most typical sites of SPCs after NPC. Methods: We searched the databases of PubMed, Web of Science, and Scopus for articles on SPCs after NPC. The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed. Results: This review includes data on 89 168 patients with NPC from 21 articles. The mean occurrence for SPCs was 6.6% and varied from 4.9% in endemic areas to 8.7% in non-endemic areas. The most frequent locations of SPCs were oral cavity, pharynx, nose and paranasal sinuses, esophagus and lung. Conclusion: There is an increased risk for a SPC after NPC management, especially in non-endemic areas. However, their mean rate is lower than after other head and neck carcinomas. [ABSTRACT FROM AUTHOR]

In 2016–2017, a large Swedish hospital introduced a mobile team of asylum social workers to work with asylum-seeking and undocumented patients. Based on interviews with the asylum social workers and the theoretical concepts of jurisdiction and professional discretion, this study explores how they experienced their work and developed their specialist competence and strategies for health social work with migrants. The findings show that they not only relieved staff and supported patients and relatives but also systemised the knowledge about health social work with migrants and created a professional specialty with a socially, rather than medically, defined group of patients. [ABSTRACT FROM AUTHOR]

Mitochondrial metabolism is entirely dependent on the biosynthesis of the [4Fe-4S] clusters, which are part of the subunits of the respiratory chain. The mitochondrial late ISC pathway mediates the formation of these clusters from simpler [2Fe-2S] molecules and transfers them to client proteins. Here, we characterized the late ISC pathway in one of the simplest mitochondria, mitosomes, of the anaerobic protist Giardia intestinalis that lost the respiratory chain and other hallmarks of mitochondria. In addition to IscA2, Nfu1 and Grx5 we identified a novel BolA1 homologue in G. intestinalis mitosomes. It specifically interacts with Grx5 and according to the high-affinity pulldown also with other core mitosomal components. Using CRISPR/Cas9 we were able to establish full bolA1 knock out, the first cell line lacking a mitosomal protein. Despite the ISC pathway being the only metabolic role of the mitosome no significant changes in the mitosome biology could be observed as neither the number of the mitosomes or their capability to form [2Fe-2S] clusters in vitro was affected. We failed to identify natural client proteins that would require the [2Fe-2S] or [4Fe-4S] cluster within the mitosomes, with the exception of [2Fe-2S] ferredoxin, which is itself part of the ISC pathway. The overall uptake of iron into the cellular proteins remained unchanged as also observed for the grx5 knock out cell line. The pull-downs of all late ISC components were used to build the interactome of the pathway showing specific position of IscA2 due to its interaction with the outer mitosomal membrane proteins. Finally, the comparative analysis across Metamonada species suggested that the adaptation of the late ISC pathway identified in G. intestinalis occurred early in the evolution this of supergroup of eukaryotes. Author summary: Anaerobic parasitic protists, such as Giardia intestinalis, have dramatically reduced their mitochondrial metabolism. Large mitochondrial networks known from aerobic eukaryotes have evolved into minimalist vesicles that are still enclosed by a double membrane but have lost the mitochondrial genome, respiratory chain, and most mitochondrial enzymes. However, these small mitochondria still contain the so-called ISC pathway, which synthesizes iron-sulfur clusters, essential cofactors for the function of respiratory chain complexes, and other mitochondrial enzymes. In this work, we have begun to characterize the ISC pathway in G. intestinalis to understand whether and why iron-sulfur clusters are formed in these small mitochondrial organelles known as mitosomes. We found that while the 'early' part of the ISC pathway responsible for the formation of the simplest [2Fe-2S] clusters is functional in mitosomes, the function of the 'late' components involved in [4Fe-4S] cluster formation remains unclear due to unknown substrates that require these clusters. Identifying the role of the "late" ISC pathway is crucial to understanding why mitosomes remain present in anaerobic eukaryotes at all. [ABSTRACT FROM AUTHOR]

Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019. Material and Methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position. Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each). Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice. [ABSTRACT FROM AUTHOR]

The World Health Organization has adopted a resolution on sepsis and urged member states to develop national processes to improve sepsis care. In Sweden, sepsis was selected as one of the ten first diagnoses to be addressed, when the Swedish government in 2019 allocated funds for patient-centred clinical pathways in healthcare. A national multidisciplinary working group, including a patient representative, was appointed to develop the patient-centred clinical pathway for sepsis. The working group mapped challenges and needs surrounding sepsis care and included a survey sent to all emergency departments (ED) in Sweden, and then designed a patient-centred clinical pathway for sepsis. The working group decided to focus on the following four areas: (1) sepsis alert for early detection and management optimisation for the most severely ill sepsis patients in the ED; (2) accurate sepsis diagnosis coding; (3) structured information to patients at discharge after sepsis care and (4) structured telephone follow-up after sepsis care. A health-economic analysis indicated that the implementation of the clinical pathway for sepsis will most likely not drive costs. An important aspect of the clinical pathway is implementing continuous monitoring of performance and process indicators. A national working group is currently building up such a system for monitoring, focusing on extraction of this information from the electronic health records systems. A national patient-centred clinical pathway for sepsis has been developed and is currently being implemented in Swedish healthcare. We believe that the clinical pathway and the accompanying monitoring will provide a more efficient and equal sepsis care and improved possibilities to monitor and further develop sepsis care in Sweden. [ABSTRACT FROM AUTHOR]

Objective To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [ P  = 2.0 × 10−4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [ P  = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [ P  = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [ P  = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients. [ABSTRACT FROM AUTHOR]

The return-to-work (RTW) process for people with multimorbidity and psychosocial difficulties can be complicated. This study explores the organisational prerequisites for coordinating these patients' RTW processes from the perspective of coordinators in different clinical areas in Sweden. Six focus group interviews were conducted with 24 coordinators working in primary healthcare (PHC), psychiatric and orthopaedic clinics. The data were analysed thematically, inspired by organisation theory. Coordinators described varying approaches to people with multimorbidity and psychosocial difficulties, with more hesitancy among PHC coordinators, who were perceived by other coordinators as hindering patient flows between clinical areas. Most organisational barriers to RTW were identified in the healthcare sector. These were long waiting times, physicians drawing up inadequate RTW plans, coordinators being involved late in the sickness absence process, and lack of rehabilitation programmes for people with multimorbidity. The barriers in relation to organisations such as Social Insurance Agency and Employment Services were caused by regulations and differing perspectives, priorities, and procedures. Our findings indicate what is needed to improve the RTW process for patients with complex circumstances: better working conditions, steering, and guidelines; shorter waiting times; and a willingness among coordinators from different clinical areas to collaborate around patients. RTW coordinators need sufficient physical and psychosocial working conditions as well as clear leadership. In order to avoid inequalities in access to RTW support, better systems are needed to identify patients who would benefit from rehabilitation and RTW coordination. There is a need for multilevel collaboration between clinical areas so that patients with multiple healthcare contacts and prolonged sickness absence can obtain support during the RTW process. [ABSTRACT FROM AUTHOR]

This study aimed to describe the incidence and prevalence of gout, describe the use of allopurinol among prevalent gout cases, and determine persistence with allopurinol and degree of compliance with treat-to-target recommendations before and after the publication of Swedish national guidelines in 2016. Prospectively registered data on gout diagnoses and allopurinol prescriptions were used to calculate incidence and prevalence, and the proportion of prevalent patients on allopurinol. Gout patients starting allopurinol during 2013–2015 versus 2016–2018 were compared regarding persistence and compliance with treat-to-target principles. The incidence of gout was 221–247 per 100 000 person-years during 2014–2019, prevalence in 2018 was 2.45%. Among prevalent cases, the proportion on allopurinol ranged from 21% to 25%. Allopurinol persistence was better for individuals starting therapy during 2016–2018 compared with 2013–2015 (45% vs 39%, p = 0.031), as were several outcomes related to treat-to-target principles, e.g. measuring baseline serum urate (SU) (84% vs 77%, p < 0.001), follow-up SU (50% vs 36%, p < 0.001), and the proportion of patients reaching an SU level < 360 µmol/L (45% vs 30%, p < 0.001). Incidence and prevalence were slightly higher than in previous Swedish reports. Allopurinol use among prevalent gout patients did not increase during 2014–2019. Only a minor improvement in persistence was seen, and a moderate increase in compliance with guidelines, suggesting a need for improved management and extended patient involvement to increase and optimize the use of urate lowering therapy. [ABSTRACT FROM AUTHOR]

Purpose: In recent decades, many countries have implemented return-to-work coordinators to combat high rates of sickness absence and insufficient collaboration in the return-to-work process. The coordinators should improve communication and collaboration between stakeholders in the return-to-work process for people on sickness absence. How they perform their daily work remains unexplored, and we know little about to what extent they collaborate and perform other work tasks to support people on sickness absence. This study examines which work models return-to-work coordinators use in primary healthcare, psychiatry and orthopaedics in Sweden. Methods: A questionnaire was sent to all 82 coordinators in one region (89% response rate) with questions about the selection of patients, individual patient support, healthcare collaboration, and external collaboration. Random forest classification analysis was used to identify the models. Results: Three work models were identified. In model A, coordinators were more likely to select certain groups of patients, spend more time in telephone than in face-to-face meetings, and collaborate fairly much. In Model B there was less patient selection and much collaboration and face-to-face meetings. Model C involved little patient selection, much telephone contact and very little collaboration. Model A was more common in primary healthcare, model C in orthopaedics, while model B was distributed equally between primary healthcare and psychiatry. Conclusion: The work models correspond differently to the coordinator's assignments of supporting patients and collaborating with healthcare and other stakeholders. The differences lie in how much they actively select patients, how much they collaborate, and with whom. Their different distribution across clinical contexts indicates that organisational demands influence how work models evolve in practice. [ABSTRACT FROM AUTHOR]

During the ongoing Covid-19 pandemic, many patients cancelled their scheduled hearing aid renewal. We offered to send them new hearing aids programmed according to the audiometric data on file. In this study we compared remote hearing aid renewal to a conventional renewal with a recent audiogram based on scores from the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire. We also examined the need for a physical visit for hearing aid adjustment in the remote group and analysed the accuracy of the pre-existing audiogram correction method using data from the control group. Retrospective chart review. 51 patients who underwent remote hearing aid renewal and 22 control patients who received office-based hearing aid renewal. IOI-HA scores were lower in the remote fitted group, but comparison with data from a Swedish nationwide database had no clinically significant differences. A follow-up physical appointment was required in only 20% of the remote group. The intraclass correlation coefficient (ICC) between the pure tone averages of the corrected former audiogram and measured audiogram was high. Remote hearing aid renewal using existing audiometric data is feasible, and most physical visits can be avoided. [ABSTRACT FROM AUTHOR]

We consider a slightly modified local finite-volume approximation of the Laplacian operator originally proposed by Chandrashekar (Int J Adv Eng Sci Appl Math 8(3):174–193, 2016, ). The goal is to prove consistency and convergence of the approximation on unstructured grids. Consequently, we propose a semi-discrete scheme for the heat equation augmented with Dirichlet, Neumann and Robin boundary conditions. By deriving a priori estimates for the numerical solution, we prove that it converges weakly, and subsequently strongly, to a weak solution of the original problem. A numerical simulation demonstrates that the scheme converges with a second-order rate. [ABSTRACT FROM AUTHOR]

In this work, direct investigation of mesoscale clusters in solution using dynamic light scattering is combined with an indirect method based on the study of primary crystal nucleation and its dependence on the conditions of solution preparation and pre-treatment. In a novel approach we have studied how the nucleation induction time of a pharmaceutical cocrystal, a 1 : 1 saccharin–carbamazepine cocrystal, depends on different preparation and pre-treatment conditions, in particular whether solutions are prepared by dissolving the cocrystal solids or the two coformers separately. Nucleation is clearly affected by some pre-treatment conditions, with longer induction times obtained for a high pre-treatment temperature and when solutions are microfiltered after dissolution. The strongest effect was observed when comparing different starting materials, with solutions prepared using cocrystals leading to much shorter induction times than solutions based on the separate coformers. DLS shows that both types of solutions contain mesoscale clusters of the order of 100–300 nm in size, but that there are clear differences in the amount of scattering indicating a higher cluster concentration in the solutions based on cocrystal solids. The results suggest the possibility that mesoscale clusters can have a structural dimension, associated with slow kinetics, which can directly affect nucleation. [ABSTRACT FROM AUTHOR]

Background: Periodontitis and oral pathogenic bacteria can contribute to the development of rheumatoid arthritis (RA). A connection between serum antibodies to Porphyromonas gingivalis (P. gingivalis) and RA has been established, but data on saliva antibodies to P. gingivalis in RA are lacking. We evaluated antibodies to P. gingivalis in serum and saliva in two Swedish RA studies as well as their association with RA, periodontitis, antibodies to citrullinated proteins (ACPA), and RA disease activity. Methods: The SARA (secretory antibodies in RA) study includes 196 patients with RA and 101 healthy controls. The Karlskrona RA study includes 132 patients with RA ≥ 61 years of age, who underwent dental examination. Serum Immunoglobulin G (IgG) and Immunoglobulin A (IgA) antibodies and saliva IgA antibodies to the P. gingivalis-specific Arg-specific gingipain B (RgpB) were measured in patients with RA and controls. Results: The level of saliva IgA anti-RgpB antibodies was significantly higher among patients with RA than among healthy controls in multivariate analysis adjusted for age, gender, smoking, and IgG ACPA (p = 0.022). Saliva IgA anti-RgpB antibodies were associated with RA disease activity in multivariate analysis (p = 0.036). Anti-RgpB antibodies were not associated with periodontitis or serum IgG ACPA. Conclusion: Patients with RA had higher levels of saliva IgA anti-RgpB antibodies than healthy controls. Saliva IgA anti-RgpB antibodies may be associated with RAdisease activity but were not associated with periodontitis or serum IgG ACPA. Our results indicate a local production of IgA anti-RgpB in the salivary glands that is not accompanied by systemic antibody production. [ABSTRACT FROM AUTHOR]

The aim of this study is to provide further validation for the weakly well-posed modified compressible Navier-Stokes system proposed in Svärd (Phys A 506:350–375, 2018) when applied to ideal gases. We do so by considering sound attenuation, both theoretically and numerically for argon and oxygen, and make comparisons with experimental values in the literature. Furthermore, we compute shock profiles for argon and nitrogen, and compare them with experiments in the literature. Our numerical simulations have revealed problems when using experimental attenuation data, as presented in the available literature, for validation and determination of diffusion coefficients. However, comparisons with the shock data, suggest that the modified system may benefit from an additional heat diffusive term. In view of these and previously published validation tests, the model proposed in Svärd (Phys A 506:350–375, 2018) is equally accurate as the standard compressible system. However, with more complete experimental information for the attenuation case at hand, it might be possible to further improve the accuracy by more precise determination of the diffusion coefficients. We propose a tentative adjustment of the model that may be tested/validated, if more detailed experimental information becomes available. [ABSTRACT FROM AUTHOR]

Parasitic nematodes pose a significant threat to human and animal health, as well as cause economic losses in the agricultural sector. The use of anthelmintic drugs, such as Ivermectin (IVM), to control these parasites has led to widespread drug resistance. Identifying genetic markers of resistance in parasitic nematodes can be challenging, but the free-living nematode Caenorhabditis elegans provides a suitable model. In this study, we aimed to analyze the transcriptomes of adult C. elegans worms of the N2 strain exposed to the anthelmintic drug Ivermectin (IVM), and compare them to those of the resistant strain DA1316 and the recently identified Abamectin Quantitative Trait Loci (QTL) on chromosome V. We exposed pools of 300 adult N2 worms to IVM (10−7 and 10−8 M) for 4 hours at 20°C, extracted total RNA and sequenced it on the Illumina NovaSeq6000 platform. Differentially expressed genes (DEGs) were determined using an in-house pipeline. The DEGs were compared to genes from a previous microarray study on IVM-resistant C. elegans and Abamectin-QTL. Our results revealed 615 DEGs (183 up-regulated and 432 down-regulated genes) from diverse gene families in the N2 C. elegans strain. Of these DEGs, 31 overlapped with genes from IVM-exposed adult worms of the DA1316 strain. We identified 19 genes, including the folate transporter (folt-2) and the transmembrane transporter (T22F3.11), which exhibited an opposite expression in N2 and the DA1316 strain and were deemed potential candidates. Additionally, we compiled a list of potential candidates for further research including T-type calcium channel (cca-1), potassium chloride cotransporter (kcc-2), as well as other genes such as glutamate-gated channel (glc-1) that mapped to the Abamectin-QTL. [ABSTRACT FROM AUTHOR]

Giardia intestinalis is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause the diarrhoeal disease giardiasis in humans and animals, but at least half of the infections are asymptomatic. However, the molecular underpinnings of these different outcomes of the infection are still poorly defined. Here, we studied the early transcriptional response to G. intestinalis trophozoites, the disease-causing life-cycle stage, in human enteroid-derived, 2-dimensional intestinal epithelial cell (IEC) monolayers. Trophozoites preconditioned in media that maximise parasite fitness triggered only neglectable inflammatory transcription in the IECs during the first hours of co-incubation. By sharp contrast, "non-fit" or lysed trophozoites induced a vigorous IEC transcriptional response, including high up-regulation of many inflammatory cytokines and chemokines. Furthermore, "fit" trophozoites could even suppress the stimulatory effect of lysed trophozoites in mixed infections, suggesting active G. intestinalis suppression of the IEC response. By dual-species RNA-sequencing, we defined the IEC and G. intestinalis gene expression programs associated with these differential outcomes of the infection. Taken together, our results inform on how G. intestinalis infection can lead to such highly variable effects on the host, and pinpoints trophozoite fitness as a key determinant of the IEC response to this common parasite. Author summary: Diarrhoeal infectious diseases are still a major problem worldwide, each year killing nearly 800,000 children. These infections are caused by a variety of pathogenic bacteria, viruses, fungi and protozoa. The protozoan parasite Giardia intestinalis is the most common eukaryotic intestinal pathogen found in humans. In contrast to most bacteria and viruses that cause diarrhoea, Giardia parasites elicit a highly variable clinical picture and often do not cause pronounced inflammation in the intestine of infected patients. Here we show, by using human intestinal epithelial cells derived from adult intestinal stem cells, that "fit" Giardia parasites can actively suppress epithelial inflammatory signalling, while their "non-fit" counterparts instead induce inflammatory responses. These two faces of the parasite are associated with specific gene expression programs and may explain the earlier observed high variability in outcome of a Giardia infection, and its modulatory effect on infection by other intestinal pathogens. [ABSTRACT FROM AUTHOR]

The AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite. [ABSTRACT FROM AUTHOR]

The aim of this article is to discuss several groups of sources which are of special interest regarding the question of Mesopotamian identities after 539 bce, towards the end of the use of cuneiform writing. In this late period, several languages and scripts were in use in Mesopotamia; therefore, groups of Akkadian, Aramaic, Greek, and Sumerian texts are discussed. The scripts used are Aramaic letters, cuneiform, and the Greek alphabet. A scholar who is interested in late Mesopotamian identities needs to take all these documents into account. This article aims at giving a brief overview on available textual material and where to find it. The topics of these texts vary from administrative documents to highly literary texts. The authors discuss Aramaic inscriptions, legal and administrative cuneiform texts, the astronomical diaries, the Seleucid Uruk scholarly texts, the late Babylonian priestly literature, Emesal cult-songs from the Hellenistic period, the Graeco-Babyloniaca (clay tablets containing cuneiform and Greek), and finally Greek inscriptions from Mesopotamia. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the author discusses articles within the issue on topics including sources regarding the question of Mesopotamian identities at the end of the cuneiform era, role of the knowledge of the dead languages of Latin and Sumerian for scribal and scholarly identities, and identity and ethnicity perspectives on the book of Ezekiel in the Hebrew Bible.

We consider an alternative Navier–Stokes model for compressible viscous ideal gases, originally proposed in [M. Svärd, A new Eulerian model for viscous and heat conducting compressible flows, Physica A 506 (2018) 350–375.] We derive a priori estimates that are sufficiently strong to support a weak entropy solution of the system. Guided by these estimates, we propose a finite-volume scheme, derive the analogous estimates and demonstrate grid convergence towards a weak entropy solution. Furthermore, this existence proof is valid for "large" initial data and no a priori assumptions on the solution are needed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate whether generalized joint hypermobility (GJH) influences postoperative results, including return to sport, patientreported outcomes, functional performance (hop tests), muscular strength, and the occurrence of ACL re-injury, in patients 1 year after anterior cruciate ligament (ACL) reconstruction. Methods: Data was extracted from a regional rehabilitation-specific registry containing information on patients with ACL injury. Patients between the ages of 16–50 years previously undergoing ACL reconstruction with available 1 year follow-up data were eligible for inclusion. Generalized joint hypermobility was assessed using the Beighton score (BS). Patients were examined one year postoperatively in terms of return to sport, patient-reported outcome, hop tests, muscular strength and the occurrence of reinjury. For purpose of analysis, patients were allocated into two groups, depending on the existence of GJH. The KOOS subscale of sports and recreation was considered the primary outcome. Analyses were performed both dichotomously and by using adjusted logistic regression, to consider potential confounders. Results: A total of 356 patients (41% males) were included, of which 76 (24% male) were categorized as having GJH. Patients with GJH had an inferior limb symmetry index preoperatively in terms of knee extension (mean 81.6 [SD 16.4] vs. 91.4 [SD 15.9], p = 0.02) and flexion strength (mean 91.9 vs. 99.1, p = 0.047) compared to patients without GJH. There was no difference between the groups in terms of the primary outcome, nor in any of the other postoperative outcomes. Nine patients (11.8%) in the group with GJH suffered ACL re-injury, compared with 13 patients (4.6%) in the control group (n.s.). Conclusion: One year after ACL reconstruction the existence of GJH did not affect postoperative patient satisfaction, strength or functional outcome. No conclusive statements can be made regarding the influence of GJH on the risk of ACL re-injury in this particular study. Level of evidence: Level II. [ABSTRACT FROM AUTHOR]

Spironucleus salmonicida is a diplomonad causing systemic infection in salmon. The first S. salmonicida genome assembly was published 2014 and has been a valuable reference genome in protist research. However, the genome assembly is fragmented without assignment of the sequences to chromosomes. In our previous Giardia genome study, we have shown how a fragmented genome assembly can be improved with long-read sequencing technology complemented with optical maps. Combining Pacbio long-read sequencing technology and optical maps, we are presenting here this new S. salmonicida genome assembly in nine near-complete chromosomes with only three internal gaps at long repeats. This new genome assembly is not only more complete sequence-wise but also more complete at annotation level, providing more details into gene families, gene organizations and chromosomal structure. This near-complete reference genome will aid comparative genomics at chromosomal level, and serve as a valuable resource for the diplomonad community and protist research. Measurement(s) genomic_DNA • sequence_assembly • sequence feature annotation Technology Type(s) SMRT Sequencing • sequence assembly process • sequence annotation Sample Characteristic - Organism Spironucleus salmonicida [ABSTRACT FROM AUTHOR]

Background: Giardia lamblia, a parasitic protist of the Metamonada supergroup, has evolved one of the most diverged endocytic compartment systems investigated so far. Peripheral endocytic compartments, currently known as peripheral vesicles or vacuoles (PVs), perform bulk uptake of fluid phase material which is then digested and sorted either to the cell cytosol or back to the extracellular space. Results: Here, we present a quantitative morphological characterization of these organelles using volumetric electron microscopy and super-resolution microscopy (SRM). We defined a morphological classification for the heterogenous population of PVs and performed a comparative analysis of PVs and endosome-like organelles in representatives of phylogenetically related taxa, Spironucleus spp. and Tritrichomonas foetus. To investigate the as-yet insufficiently understood connection between PVs and clathrin assemblies in G. lamblia, we further performed an in-depth search for two key elements of the endocytic machinery, clathrin heavy chain (CHC) and clathrin light chain (CLC), across different lineages in Metamonada. Our data point to the loss of a bona fide CLC in the last Fornicata common ancestor (LFCA) with the emergence of a protein analogous to CLC (GlACLC) in the Giardia genus. Finally, the location of clathrin in the various compartments was quantified. Conclusions: Taken together, this provides the first comprehensive nanometric view of Giardia's endocytic system architecture and sheds light on the evolution of GlACLC analogues in the Fornicata supergroup and, specific to Giardia, as a possible adaptation to the formation and maintenance of stable clathrin assemblies at PVs. [ABSTRACT FROM AUTHOR]

It is becoming evident that primary nucleation of crystals of organic molecules from solution is often anything but 'classical' in its complexity. It is also becoming increasingly clear that mesoscopic clusters of molecules are at least partly involved in the phenomenon. On-going advances are rapidly enabling these clusters to be investigated with ever more accuracy. However, despite numerous recent studies, fundamental knowledge of the properties, thermodynamics and kinetics of these clusters, and of their role in nucleation, is still limited. [ABSTRACT FROM AUTHOR]

Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P  = 6.3 × 10−61, odds ratio (OR) 0.10; rs9277341, P  = 1.5 × 10−44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P  = 2.7 × 10−10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P  = 5.4 × 10−25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P  = 7.9 × 10−7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types. [ABSTRACT FROM AUTHOR]

Electric powertrains in terms of battery electric vehicles (BEV) are considered to be very interesting for heavy truck transportations. The challenge is the need for very large onboard energy and batteries. Long-term fuel cells (FCs) are considered an interesting support system for heavy-duty BEV, but in the short term, a range extender (REX) is also interesting. A heavy-duty BEV with 970 kWh batteries installed can handle 27% of all possible missions for the Scania fleet considering daily recharging. The back-up range extender (BUREX) can expand this figure to 55% utilized 20 days per year. If a customer has a few very energy-demanding use cases each year and does not want to pay for all the batteries needed, the BUREX may be an especially good option. The BUREX reduces life-cycle CO2 emissions, irrespective of the generation mix of the grid supplying the electricity used in vehicle manufacturing and battery charging. The BUREX reuse of the existing electric components of the BEV powertrain enables the installation of a 10% larger battery pack while being 80% less costly. The BUREX also adds redundancy to the BEV concept while recharging infrastructure improves, especially in rural places. These results indicate that the BUREX concept is a powerful short-term solution that could enable greater use of HD FC and BEV trucks while charging infrastructure and FC technologies gradually become more mature. [ABSTRACT FROM AUTHOR]

Background: The nematode Parascaris univalens is one of the most prevalent parasitic pathogens infecting horses but anthelmintic resistance undermines treatment approaches. The molecular mechanisms underlying drug activity and resistance remain poorly understood in this parasite since experimental in vitro models are lacking. The aim of this study was to evaluate the use of Caenorhabditis elegans as a model for P. univalens drug metabolism/resistance studies by a comparative gene expression approach after in vitro exposure to the anthelmintic drug ivermectin (IVM). Methods: Twelve adult P. univalens worms in groups of three were exposed to ivermectin (IVM, 10–13 M, 10–11 M, 10–9 M) or left unexposed for 24 h at 37 °C, and total RNA, extracted from the anterior end of the worms, was sequenced using Illumina NovaSeq. Differentially expressed genes (DEGs) involved in metabolism, transportation, or gene expression with annotated Caernorhabditis elegans orthologues were identified as candidate genes to be involved in IVM metabolism/resistance. Similarly, groups of 300 adult C. elegans worms were exposed to IVM (10–9 M, 10–8 M and 10–7 M) or left unexposed for 4 h at 20 °C. Quantitative RT-PCR of RNA extracted from the C. elegans worm pools was used to compare against the expression of selected P. univalens candidate genes after drug treatment. Results: After IVM exposure, 1085 DEGs were found in adult P. univalens worms but the relative gene expression changes were small and large variabilities were found between different worms. Fifteen of the DEGs were chosen for further characterization in C. elegans after comparative bioinformatics analyses. Candidate genes, including the putative drug target lgc-37, responded to IVM in P. univalens, but marginal to no responses were observed in C. elegans despite dose-dependent behavioral effects observed in C. elegans after IVM exposure. Thus, the overlap in IVM-induced gene expression in this small set of genes was minor in adult worms of the two nematode species. Conclusion: This is the first time to our knowledge that a comparative gene expression approach has evaluated C. elegans as a model to understand IVM metabolism/resistance in P. univalens. Genes in P. univalens adults that responded to IVM treatment were identified. However, identifying conserved genes in P. univalens and C. elegans involved in IVM metabolism/resistance by comparing gene expression of candidate genes proved challenging. The approach appears promising but was limited by the number of genes studied (n = 15). Future studies comparing a larger number of genes between the two species may result in identification of additional candidate genes involved in drug metabolism and/or resistance. [ABSTRACT FROM AUTHOR]

Giardia intestinalis is a protozoan parasite causing diarrheal disease, giardiasis, after extracellular infection of humans and other mammals' intestinal epithelial cells (IECs) of the upper small intestine. The parasite has two main life cycle stages: replicative trophozoites and transmissive cysts. Differentiating parasites (encysting cells) and trophozoites have recently been shown to be present in the same regions of the upper small intestine, whereas most mature cysts are found further down in the intestinal system. To learn more about host-parasite interactions during Giardia infections, we used an in vitro model of the parasite's interaction with host IECs (differentiated Caco-2 cells) and Giardia WB trophozoites, early encysting cells (7 h), and cysts. Dual RNA sequencing (Dual RNAseq) was used to identify differentially expressed genes (DEGs) in both Giardia and the IECs, which might relate to establishing infection and disease induction. In the human cells, the largest gene expression changes were found in immune and MAPK signaling, transcriptional regulation, apoptosis, cholesterol metabolism and oxidative stress. The different life cycle stages of Giardia induced a core of similar DEGs but at different levels and there are many life cycle stage-specific DEGs. The metabolic protein PCK1, the transcription factors HES7, HEY1 and JUN, the peptide hormone CCK and the mucins MUC2 and MUC5A are up-regulated in the IECs by trophozoites but not cysts. Cysts specifically induce the chemokines CCL4L2, CCL5 and CXCL5, the signaling protein TRKA and the anti-bacterial protein WFDC12. The parasite, in turn, up-regulated a large number of hypothetical genes, high cysteine membrane proteins (HCMPs) and oxidative stress response genes. Early encysting cells have unique DEGs compared to trophozoites (e.g. several uniquely up-regulated HCMPs) and interaction of these cells with IECs affected the encystation process. Our data show that different life cycle stages of Giardia induce different gene expression responses in the host cells and that the IECs in turn differentially affect the gene expression in trophozoites and early encysting cells. This life cycle stage-specific host-parasite cross-talk is an important aspect to consider during further studies of Giardia 's molecular pathogenesis. [ABSTRACT FROM AUTHOR]

The recovery of scandium from waste streams of mining and metallurgical operations presents an opportunity to balance supply and demand of this commodity. This study expands on the research focusing on the recovery of scandium as (NH4)3ScF6 from strip liquors by antisolvent crystallization using ethanol as the antisolvent. The effect of process conditions including reducing the rate of supersaturation generation, agitation mechanism, feeding point location with respect to local supersaturation, and seeding are assessed with emphasis on the final crystal size distributions (CSD) and morphology. Reducing the rate of supersaturation generation by reducing the ethanol concentration and by controlling the rate of antisolvent addition had the greatest effect on increasing the crystal sizes, although broader CSDs were obtained. Morphological modifications, without polymorphic transformations, were also observed when one-pot addition of 60 or 70% v/v ethanol was conducted, but not observed when the dilute antisolvents were fed at a controlled low addition rate. [ABSTRACT FROM AUTHOR]