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PURPOSE: The effect of climate-driven events, such as wildfires, on health care delivery and cancer care is a growing concern. Patients with cancer undergoing radiation therapy are particularly vulnerable to treatment interruptions, which have a direct effect on survival. We report the results of a study characterizing the effect of wildfires on radiation oncology clinics and their patients. METHODS AND MATERIALS: A survey of California radiation oncologists was used to evaluate emergency preparedness and the effect of wildfires on the delivery of radiation therapy services between 2017 and 2022. Descriptive statistics and Pearsons χ2 tests were performed to investigate potential relationships between provider characteristics, practice settings, and perceptions of the effect of wildfire events. California Department of Forestry and Fire Protection data were employed to map the geographic distribution of wildfires to clinic locations. RESULTS: Response rate was 12.3% (51/415 radiation oncologists), representing 25% of clinics (43/176) in 41% (24/58) of California counties. Sixty-one percent (31/51) of respondents reported being affected by a wildfire, 2 of which are rural clinics (100%, 2/2) and 29 are (59%, 29/49) metropolitan practices. Of these, 18% (9/51) reported a clinic closure, and 29% (15/51) reported staffing shortages. Respondents reported effects on patients, including having to evacuate (55%, 28/51), cancel/reschedule treatments (53%, 27/51), and experiencing physical, mental, or financial hardship due to wildfires (45%, 23/51). Respondents described effects on clinical operations, including being forced to transfer patients (24%, 12/51), transportation interruptions (37%, 19/51), regional/community evacuations (35%, 18/51), and physical/mental health effects (27%, 14/51) on clinic personnel. Less than half of the respondents (47%, 24/51) reported their workplace had a wildfire emergency preparedness plan. Additionally, geographic analysis revealed that 100% (176/176) of clinics were located within 25 miles of a wildfire. CONCLUSIONS: This study highlights the effects of wildfires on radiation oncology clinics and patients and underscores the need for emergency preparedness planning to minimize the consequences of such disasters.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

This article presents a series of recommendations for the publication of archaeological data, to improve their usability. These 12 recommendations were formulated by archaeological data experts who mined thousands of publications for different data types (including funerary practices, accelerator mass spectrometry dating, stable isotopes, zooarchaeology, archaeobotany and pathologies) during the initial construction of the Big Interdisciplinary Archaeological Database (BIAD). We also include data harmonisation vocabularies utilised for the integration of data from different recording systems. The case studies we cite to illustrate the recommendations are grounded in examples from the published literature and are presented in a problem/solution format. Though practically oriented towards the facilitation of efficient databasing, these recommendations – which we refer to as the BIAD Standards – are broadly applicable by those who want to extract scientific data from archaeological information, those who work with a specific region or theoretical focus and journal editors and manuscript authors. We anticipate that the use of the BIAD Standards will increase the usability, visibility, interoperability and longevity of published data and also increase the citations of those publications from which data were mined. The Standards will also help frame a unified foundation to support the continued integration of the natural sciences with archaeological research in the future.

Students experience the research-teaching nexus differently as they progress through their first three years of undergraduate study depending on the discipline. The question is if students, within the same discipline, experience the nexus differently depending on the profile of the institution where they study. The present study explored students' experiences of the research-teaching nexus (RT-nexus) during their undergraduate studies at one research-intensive and one teaching-intensive university. A survey (n = 340) was distributed among business students at two Swedish universities. One finding is that students from both universities reported on a progression in how they experience the nexus, and in learning outcomes. Students also rated what teachers do and what they themselves do higher, than what their peers do. The main gap between students from the two universities was that students from the research-intensive university generally perceived a stronger connection between teaching and research than did students from the teaching-intensive university. They also to a higher extent found that a close connection between research and teaching in their education would be important to them in their future work life, whereas students from the teaching-intensive university were more unsure.

ABSTRACT Introduction The aim of this prospective cohort study was to investigate the associations between changes in cardiorespiratory fitness (CRF) and the risk of colorectal and prostate cancer in men. Methods Data from men who completed a health assessment both in military conscription in youth and an occupational health profile assessment (HPA) later in life were used. CRF was assessed as estimated V̇O2max, using a cycle ergometer fitness test at both time points. We linked the assessment data to national register data on colorectal and prostate cancer incidence, and hazard ratios and confidence intervals were estimated using Cox proportional hazard regression. Results 139,764 men with a mean age of 18 (SD 0.6) at conscription and 43 (SD 8.9) at HPA were included. The average time between the two assessments was 25.9 (SD 9.0) years and mean follow‐up time following HPA test was 10.0 (SD 5.6) years for prostate and colorectal cancer. Annual percentage change in relative and absolute V̇O2max from conscription to HPA was inversely associated with the risk of colorectal cancer incidence, hazard ratio of 0.83 (95% CI [0.72–0.94]) and 0.88 (95% CI [0.79–0.99]), respectively. These associations were driven by data from individuals in the lowest and moderate level fitness tertials at conscription. Change in CRF was not associated with prostate cancer incidence risk. Conclusions Changes in, not only level of, CRF from youth to adulthood are related to colorectal cancer incidence risk and therefore, improving CRF should be considered as an important colorectal cancer risk reduction strategy.

Summary: Norway rats are known to liberate trapped conspecifics, which implies an empathic response to the deplorable situation of the captive. If this is an altruistic behavior reflecting an evolved decision rule, the requisite fitness enhancement to the actor may result either from close relatedness or the expectation of future returns. Neither potential effects of relatedness nor of reciprocal returns have yet been examined. Our two-stage experiment revealed that wild-type Norway rats preferably collaborated with partners that had previously freed them from a trap and subsequently cooperated with each other, indicating that expected future benefits may underlie the deliverance of trapped companions. Relatedness had no effect on their cooperative propensity. These results show that rats recruit partners to coordinate cooperation by direct reciprocity but not kin discrimination, suggesting that the evolutionary mechanism responsible for the altruistic liberation behavior of Norway rats may be reciprocal altruism rather than kin selection.

Pharmacies are currently unable to stock proper oral dosage forms for pediatric populations. This leads to manipulation of medications or the need to compound specialized medications, which can be a time-consuming process. Using Semisolid Extrusion (SSE) additive manufacturing (AM), specialized medications can be produced in an expedited process from off-the shelf medication in a hospital or outpatient pharmacy setting. In this study, tablets with a desired dose of 5 mg of metoprolol tartrate derived from commercial Seloken™ 50 mg tablets were 3D printed in a hospital setting. Validation testing was done on five batches, highlighting tablets with a high uniformity in mass and dimension, drug content, acceptable microbial assays, and prolonged release during in-vitro analysis. The average drug content found for the tablets was within ±6% of 5 mg for all batches produced. Comparisons were done between the SSE tablets and capsules produced in an external compounding facility, highlighting several positive aspects of SSE-produced tablets beyond simply shortening the production timeline. The SSE tablets printed in this study are characterized by their smaller size, enhanced prolonged release properties, and more uniform drug content across the tested samples. Additionally, interviews with pharmaceutical professionals were conducted to determine the positive aspects of SSE and further improvements to bring this technique as seamlessly as possible into the pharmacy. This study underscores the feasibility of employing SSE in the production of specialized medications within a hospital environment. Furthermore, it highlights the methodological advantages SSE offers over existing production standards, demonstrating its potential to improve pharmaceutical manufacturing in healthcare settings.

Impaired rennet coagulation properties in milk could lead to prolonged processing times and production losses. Heritability for milk coagulation has previously been estimated to be 0.28 to 0.45, indicating that genetic selection can be used to manipulate this trait. The CN proteins are expressed by the genes CSN1S1, CSN2, CSN1S2, and CSN3 and are located on bovine chromosome 6. To better understand the effect of genetic variation in the CN genes on milk coagulation, blood and milk samples from 30 Swedish Red Dairy Cattle (RDC) with divergent coagulation properties were investigated. DNA from the 30 cows was sequenced for the CN genes to determine the theoretical AA sequence and to look for genetic variation in the untranslated regions. The aim is to confirm the protein genetic variants previously reported, while searching for additional genetic variation in the CN genes of 30 RDC. We observed genetic variation in 116 SNPs in the known CN genes where 10% of the SNPs are exon variants and the remaining 90% are intron variants. A total of 2.5% of the SNPs are found in the 5′- or 3′-untranslated region (UTR) regions of the exons; 2% are synonymous variants and 6% are missense variants that concurred with the known protein variants for CSN1S1, CSN2, and CSN3. Furthermore, 6% of the SNPs are splice polypyrimidine tract intron variants. The 2 genetic variants in the 5′- and 3′-UTR in CSN1S1 and CSN3 are found with protein variants CSN1S1C and CSN3B. Because both UTR variants are associated with gain and loss of micro RNA and transcription factors, this could explain differences in expression of the genetic protein variants. Preliminary chi-squared analysis and comparison with previous GWAS studies showed potential connections between the identified SNPs and coagulation properties of milk. By advancing the knowledge of the connection between the DNA sequence and the functional properties of the CN proteins, we hope to learn more about the cheese coagulation properties of milk from RDC.

Background: Evidence on how decisions regarding escalation to triple therapy and de- or re-escalation are taken and the rationale on which these decisions are based is currently limited in Germany. Objectives: The TETRIS study aims to elucidate influences on treatment decisions surrounding triple therapy in a real-world practice setting in Germany. Design: TETRIS is an ongoing, multicenter, prospective, observational cohort study recruiting patients with chronic obstructive pulmonary disease (COPD) with or without asthma who have already been treated with triple therapy for 2–48 weeks. Methods: For better representation of the treatment reality in Germany, patients are recruited from general practitioners and pulmonologists. Data are collected in two parts. Part 1 involves cross-sectional phenotyping of patients at enrollment. Part 2 involves a 2-year longitudinal follow-up period to monitor/document all visits by the patients during the 24-month observation period per routine clinical practice. Here, we report the demographic and baseline characteristics of 1213 eligible patients recruited to part 1 of the study. Results: The mean patient age was 66.4 years overall, and 29.3% (356/1213) of patients had no comorbidities. The mean CAT score was 19.4; the number of exacerbations and hospitalizations due to exacerbations in the past 3 years before starting triple therapy was 0.6 and 0.1, respectively. Dual bronchodilation with a long-acting muscarinic antagonist (LAMA) plus a long-acting β-2 agonist (LABA) was the most common therapy for COPD before initiation of triple therapy in 58.3% of patients. Conclusion: In this real-world setting in Germany, patients with COPD have a relatively low reported exacerbation rate but high symptom burden, and over 70% are multimorbid. Triple therapy is initiated in patients who are primarily highly symptomatic despite being on LAMA + LABA. Future prospective studies in patients with multimorbidity are warranted to better understand the treatment landscape across the disease spectrum. Trial registration: https://clinicaltrials.gov/study/NCT04657211

Objectives: To assess inter- and intrarater reliability and agreement for measurements of root lengths using multiplanar reconstruction (MPR) in cone beam computed tomography (CBCT) examinations. Furthermore, to determine whether using MPR from different CBCT machines was a reliable and reproducible method for assessment of root length during orthodontic treatment of adolescents. Materials and methods: A total of 40 CBCT examinations obtained before, during and after orthodontic treatment of 14 adolescents, with fixed appliances from a multicentre randomised controlled trial, were used. All roots from the incisors to the first molars were measured by two independent raters and in accordance with a protocol preceded by a multi-step calibration. Reliability was assessed by intra class correlation (ICC). Agreement was assessed by measurement error according to the Dahlberg formula and Bland–Altman plot. Results: The number of repeated measurements varied from 436 to 474 for the different timepoints. Good to excellent inter- and intrarater reliability for different tooth groups and timepoints were shown. Measurement error for inter- and intrarater agreement varied between 0.41 mm and 0.77 mm. The Bland–Altman plot with 95% limits of agreement varied between +1.43 mm and −2.01 mm for different tooth groups and timepoints. Conclusions: The results of this study indicate that CBCT using MPR from different machines is a reproducible method for measuring root length during different phases of orthodontic treatment. When interpreting root shortening measurements in CBCT using MPR for clinical or research purposes, values below 2 mm should be approached with caution, as they may contain measurement errors.

Introduction Surgical treatment of distal femoral fractures (DFFs) in osteoporotic bone is challenging despite improvements in hardware and surgical techniques. The occurrence and degree of secondary displacement during healing after bridging plate fixation are still unknown. This study aimed to assess the occurrence and degree of secondary displacement in healing DFFs in elderly patients and correlate the secondary displacement to body mass index, bone density, and weight-bearing regimen. Patients and Methods The study involved 32 patients, 65 years or older, with a DFF of AO/OTA types 33 A2-3, B1-2, C1-2, and 32(c) A-C,1-3, including peri-prosthetic fractures with stable implants. Twenty-seven patients had at least 8 weeks of follow-up, and 21 patients had a complete 1-year follow-up. Minimally invasive surgery was performed using a distal anatomical femoral plate as a long bridge-plating construct. Secondary displacement was assessed with computed tomography of the entire femur postoperatively and at 8, 16, and 52 weeks. Femoral length, coronal angulation (varus/valgus), and subsidence as the change in distance between the distal joint surface and a specified locking screw were measured. Results There was a statistically significant mean femoral shortening at 52 weeks of 4.7 mm (SD 3.9, (95% CI 2.9–6.5), P < 0.001) mainly by subsidence of the distal fragment. Most patients experienced limited coronal angulation. There was no correlation between body mass index or bone density and secondary displacement. At the 1-year follow-up, no patient needed revision surgery for non-union or plate breakage. Restricted weight-bearing for 8 weeks did not prevent secondary displacements or adverse events such as cut-outs. Conclusion Modern dynamic plate osteosynthesis could not prevent commonly occurring fracture subsidence in DFF in an elderly cohort. Restricted weight-bearing for 8 weeks did not prevent secondary displacements or mechanical adverse events.

EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.

Objective: Exposure of adipocytes to ‘cool’ temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (Scd1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. The goal of this study is to further investigate the roles of Scd in adipocytes. Method: In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological Scd1 inhibition to dissect the enzyme's function in adipocyte physiology. Results: Our study reveals that production of monounsaturated lipids by Scd1 is necessary for fusion of autophagosomes to lysosomes and that with a Scd1-deficiency, autophagosomes accumulate. In addition, Scd1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of Scd1-deficient adipocytes. Conclusion: This study demonstrates the indispensable role of Scd1 in adipocyte survival, with its inhibition in vivo triggering autophagy-dependent cell death and its depletion in vivo leading to the loss of bone marrow adipocytes.

Abstract Sickness absence from work has a large adverse impact on both individuals and societies in Sweden and the costs for sickness absence were calculated to 64.6 billion Swedish kronor (approx. 5.6 billion in Euros) in 2020. Although high cardiorespiratory fitness may protect against potential adverse effects of high physical workload, research on the moderating effect of respiratory fitness in the relation between having an occupation with high physical workload and sickness absence is scarce. To study the moderating effect of cardiorespiratory fitness in the association between occupation and psychiatric, musculoskeletal, and cardiorespiratory diagnoses. Data was retrieved from the HPI Health Profile Institute database (1988–2020) and Included 77,366 participants (mean age 41.8 years, 52.5% women) from the Swedish workforce. The sample was chosen based on occupational groups with a generally low education level and differences in physical workload. Hurdle models were used to account for incident sickness absence and the rate of sickness absence days. There were differences in sickness absence between occupational groups for musculoskeletal and cardiorespiratory diagnoses, but not for psychiatric diagnoses. In general, the association between occupation and musculoskeletal and cardiorespiratory diagnoses was moderated by cardiorespiratory fitness in most occupational groups with higher physical workload, whereas no moderating effect was observed for psychiatric diagnoses. The study results encourage community and workplace interventions to both consider variation in physical workload and to maintain and/or improve cardiorespiratory fitness for a lower risk of sickness absence, especially in occupations with high physical workload.

Abstract Background Genetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting. Methods Women with suspected HBOC referred from all oncogenetic clinics in Sweden over a six-year inclusion period were screened for PVs in 13 clinically relevant genes. The genetic outcome was compared with tumor characteristics and other clinical data collected from national cancer registries and hospital records. Results In 4622 women with breast and/or ovarian cancer the overall diagnostic yield (the proportion of women carrying at least one PV) was 16.6%. BRCA1/2 PVs were found in 8.9% of women (BRCA1 5.95% and BRCA2 2.94%) and PVs in the other breast and ovarian cancer predisposition genes in 8.2%: ATM (1.58%), BARD1 (0.45%), BRIP1 (0.43%), CDH1 (0.11%), CHEK2 (3.46%), PALB2 (0.84%), PTEN (0.02%), RAD51C (0.54%), RAD51D (0.15%), STK11 (0) and TP53 (0.56%). Thus, inclusion of the 11 genes in addition to BRCA1/2 increased diagnostic yield by 7.7%. The yield was, as expected, significantly higher in certain subgroups such as younger patients, medullary breast cancer, higher Nottingham Histologic Grade, ER-negative breast cancer, triple-negative breast cancer and high grade serous ovarian cancer. Age and tumor subtype distributions differed substantially depending on genetic finding. Conclusions This study contributes to understanding the clinical and genetic landscape of breast and ovarian cancer susceptibility. Extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer predisposition genes almost doubles the diagnostic yield, which has implications for genetic counseling and clinical guidelines. The very low yield in the syndrome genes CDH1, PTEN and STK11 questions the usefulness of including these genes on routine gene panels.

Little is known about the extent of variation and activity of naturally occurring milk glycosidases and their potential to degrade milk glycans. A multi-omics approach was used to investigate the relationship between glycosidases and important bioactive compounds such as free oligosaccharides and O-linked glycans in bovine milk. Using 4-methylumbelliferone (4-MU) assays activities of eight indigenous glycosidases were determined, and by mass spectrometry and 1H NMR spectroscopy various substrates and metabolite products were quantified in a subset of milk samples from eight native North European cattle breeds. The results showed a clear variation in glycosidase activities among the native breeds. Interestingly, negative correlations between some glycosidases including β-galactosidase, N-acetyl-β-d-glucosaminidase, certain oligosaccharide isomers as well as O-linked glycans of κ-casein were revealed. Further, a positive correlation was found for free fucose content and α-fucosidase activity (r = 0.37, p-value < 0.001) indicating cleavage of fucosylated glycans in milk at room temperature. The results obtained suggest that milk glycosidases might partially degrade valuable glycans, which would result in lower recovery of glycans and thus represent a loss for the dairy ingredients industry if these activities are pronounced.

Stephanie Korn,1 Katrin Milger,2 Dirk Skowasch,3 Christian Schulz,4 Cordula Mohrlang,5 Martin Wernitz,5 Thomas Paulsson,6 Michael Hennig,5 Roland Buhl7 1IKF Pneumologie Mainz, Mainz and Thoraxklinik Heidelberg, Heidelberg, Germany; 2Department of Medicine V, University Hospital, LMU Munich, Munich and Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; 3University Hospital Bonn, Pneumology, Bonn, Germany; 4University Hospital Regensburg, Internal Medicine II, Pneumology, Regensburg, Germany; 5GlaxoSmithKline GmbH & Co. KG, Munich, Germany; 6GlaxoSmithKline Plc, Brentford, UK; 7Pulmonary Department, Johannes Gutenberg University Mainz, Mainz, GermanyCorrespondence: Cordula Mohrlang, GlaxoSmithKline GmbH & Co. KG, Prinzregentenplatz 9, München, D-81675, Germany, Tel + 49 163 360 5201, Email cordula.c.mohrlang@gsk.comPurpose: The German Asthma Net (GAN) operates a Severe Asthma Registry that provides an overview of the clinical presentation and management of patients with severe asthma. Based upon data from the GAN registry, the MepoGAN study aimed to describe clinical profiles and treatment outcomes of patients who were treated with the anti-IL-5 monoclonal antibody mepolizumab (NucalaTM) in routine practice in Germany.Patients and Methods: The MepoGAN study is a descriptive retrospective non-interventional cohort study. Mepolizumab patients enrolled in the GAN registry were evaluated with results being described in two different data sets: Cohort 1 (n=131) started on mepolizumab when the patients entered the registry. Results were reported after 4 months of therapy. Patients in Cohort 2 (n=220) were on treatment with mepolizumab at the time of enrollment and follow-up data were collected after a further year of treatment. Outcome measures included asthma control, lung function, disease symptoms, OCS use, and exacerbations.Results: Patients enrolled in the registry who started on mepolizumab in Cohort 1 had a mean age of 55 years, were former smokers in 51% of the cases, had a mean blood eosinophil count of 500 cells/μL, and frequently had maintenance OCS use (55%). In this real-world setting, mepolizumab therapy was associated with a clinically relevant reduction in blood eosinophils (− 445.7 cells/μL), OCS use (− 30%), and improvement in asthma control. Fifty-five percent (vs 10% at baseline) of the patients reported controlled or partially controlled asthma 4 months after starting therapy. In patients who were already treated with mepolizumab at registry enrollment (Cohort 2), asthma control and lung function remained stable after a further year of observation.Conclusion: The GAN registry data confirm the effectiveness of mepolizumab in a real-world setting. Treatment benefits are maintained over time. While the asthma of patients treated in routine practice was more severe, the results observed with mepolizumab are broadly consistent with RCTs.Keywords: severe asthma, registry, real-world, mepolizumab, patient profile, asthma control

Milk oligosaccharides are of high interest due to their bioactive properties. This study is the first to characterise milk oligosaccharides from native North European cattle breeds, as represented by 80 milk samples collected from eight native breeds originated from Norway (Norwegian Doela cattle and Norwegian Telemark cattle), Sweden (Swedish Mountain cattle), Denmark (Danish Red anno 1970), Iceland (Icelandic cattle), Lithuania (native Lithuanian Black and White) and Finland (Western Finncattle and Eastern Finncattle). Using high-performance liquid-chromatography chip/quadrupole time-of-flight mass-spectrometry, 18 unique monosaccharide compositions and a multitude of isomers were identified. No N-glycolylneuraminic acid was identified among these breeds. Western Finncattle milk was most abundant in neutral, acidic and fucosylated oligosaccharides. Further, Eastern Finncattle milk was significantly higher in acidic oligosaccharides and Icelandic cattle milk significantly higher in fucosylated oligosaccharides, compared to the mean. This study highlights specific native breeds of particular interest for future exploitation of milk oligosaccharides and breeding strategies.