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1.	Carraminana, Albert, et al. (författare) Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV) 2019 Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502 Tidskriftsartikel (refereegranskat)abstract Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
2.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
3.	2017 swepub:Mat__t
4.	Allentoft, Morten E., et al. (författare) Population genomics of post-glacial western Eurasia 2024 Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311 Tidskriftsartikel (refereegranskat)abstract 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.
5.	Bernal, Ximena E., et al. (författare) Empowering Latina scientists 2019 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
6.	Ferrando, Carlos, et al. (författare) Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial 2020 Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120 Tidskriftsartikel (refereegranskat)abstract Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
7.	Nishi, Stephanie K., et al. (författare) Mediterranean, DASH, and MIND Dietary Patterns and Cognitive Function : The 2-Year Longitudinal Changes in an Older Spanish Cohort 2021 Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13 Tidskriftsartikel (refereegranskat)abstract Background and Aims: Plant-forward dietary patterns have been associated with cardiometabolic health benefits, which, in turn, have been related to cognitive performance with inconsistent findings. The objective of this study was to examine the relationship between baseline adherence to three a priori dietary patterns (Mediterranean, DASH, and MIND diets) with 2-year changes in cognitive performance in older adults with overweight or obesity and high cardiovascular disease risk. Methods: A prospective cohort analysis was conducted within the PREDIMED-Plus trial, involving 6,647 men and women aged 55–75 years with overweight or obesity and metabolic syndrome. Using a validated, semiquantitative 143-item food frequency questionnaire completed at baseline, the dietary pattern adherence scores were calculated. An extensive neuropsychological test battery was administered at baseline and 2-year follow-up. Multivariable-adjusted linear regression models were used to assess associations between 2-year changes in cognitive function z-scores across tertiles of baseline adherence to the a priori dietary patterns. Results: Adherence to the Mediterranean diet at baseline was associated with 2-year changes in the general cognitive screening Mini-Mental State Examination (MMSE, β: 0.070; 95% CI: 0.014, 0.175, P-trend = 0.011), and two executive function-related assessments: the Trail Making Tests Part A (TMT-A, β: −0.054; 95% CI: −0.110, − 0.002, P-trend = 0.047) and Part B (TMT-B, β: −0.079; 95% CI: −0.134, −0.024, P-trend = 0.004). Adherence to the MIND diet was associated with the backward recall Digit Span Test assessment of working memory (DST-B, β: 0.058; 95% CI: 0.002, 0.114, P-trend = 0.045). However, higher adherence to the DASH dietary pattern was not associated with better cognitive function over a period of 2 years. Conclusion: In older Spanish individuals with overweight or obesity and at high cardiovascular disease risk, higher baseline adherence to the Mediterranean dietary pattern may be associated with better cognitive performance than lower adherence over a period of 2 years.
8.	Angenendt, Linus, et al. (författare) Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia : A Pooled Analysis of Individual Patient Data From Nine International Cohorts 2019 Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 37:29, s. 2632-2642 Tidskriftsartikel (refereegranskat)abstract PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.
9.	Forslund, Sofia K., et al. (författare) Combinatorial, additive and dose-dependent drug–microbiome associations 2021 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505 Tidskriftsartikel (refereegranskat)abstract During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
10.	Leonard, Hampton L., et al. (författare) The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data 2023 Ingår i: npj Parkinson's Disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.
11.	Monelli, Erika, et al. (författare) Angiocrine polyamine production regulates adiposity 2022 Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 4:3, s. 327- Tidskriftsartikel (refereegranskat)abstract Reciprocal interactions between endothelial cells (ECs) and adipocytes are fundamental to maintain white adipose tissue (WAT) homeostasis, as illustrated by the activation of angiogenesis upon WAT expansion, a process that is impaired in obesity. However, the molecular mechanisms underlying the crosstalk between ECs and adipocytes remain poorly understood. Here, we show that local production of polyamines in ECs stimulates adipocyte lipolysis and regulates WAT homeostasis in mice. We promote enhanced cell-autonomous angiogenesis by deleting Pten in the murine endothelium. Endothelial Pten loss leads to a WAT-selective phenotype, characterized by reduced body weight and adiposity in pathophysiological conditions. This phenotype stems from enhanced fatty acid beta-oxidation in ECs concomitant with a paracrine lipolytic action on adipocytes, accounting for reduced adiposity. Combined analysis of murine models, isolated ECs and human specimens reveals that WAT lipolysis is mediated by mTORC1-dependent production of polyamines by ECs. Our results indicate that angiocrine metabolic signals are important for WAT homeostasis and organismal metabolism. Endothelial cells in white adipose tissue are shown to produce polyamines, which regulate adipocyte lipolysis, thus demonstrating how local angiocrine signals contribute to healthy adipose tissue homeostasis.
12.	Pierrotti, Ligia C., et al. (författare) Efficacy of beta-lactam/beta-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project) 2021 Ingår i: Transplant Infectious Disease. - : John Wiley & Sons. - 1398-2273 .- 1399-3062. ; 23:3 Tidskriftsartikel (refereegranskat)abstract Background Whether active therapy with beta-lactam/beta-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. Methods We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. Results Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count <= 500 cells/mu L at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. Conclusions Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
13.	van de Burgt, Nikita, et al. (författare) Psychiatric manifestations of inborn errors of metabolism : A systematic review 2023 Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634. ; 144 Forskningsöversikt (refereegranskat)abstract Inborn errors of metabolism (IEMs) are characterized by deficits in metabolic enzymes as a result of an inherited disease, leading to the accumulation or decreased excretion of proteins, carbohydrates and lipids. Although IEMs are often diagnosed during childhood, adolescent and adult onset variants may be accompanied by less somatic and more psychiatric manifestations, which often hampers recognition by psychiatrists of the distinction between a primary and secondary psychiatric disorder. To help clinicians in the diagnostic process, we aimed to provide an overview of psychiatric manifestations in IEMs. Our literature search yielded 4380 records in total, of which 88 studies were included in the qualitative synthesis. Reported psychiatric disorders in adolescent and adult IEMs included depression, anxiety disorder, psychosis, attention deficit hyperactivity disorder, autism spectrum disorder, bipolar disorder and obsessive-compulsive disorder as assessed by semi-structured diagnostic interviews and validated questionnaires. A diagnostic screener and multidisciplinary IEM clinics are proposed to help clinicians during the diagnostic process, to prevent diagnostic delay and to raise awareness of the psychiatric manifestations among IEMs.
14.	Agudo, Antonio, et al. (författare) No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European prospective investigation into cancer and nutrition. 2006 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1055-9965 .- 1538-7755. ; 15:5, s. 1043-5 Tidskriftsartikel (refereegranskat)
15.	Almanza-Aguilera, Enrique, et al. (författare) Intake of the total, classes, and subclasses of (poly)phenols and risk of prostate cancer : a prospective analysis of the EPIC study 2023 Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:16 Tidskriftsartikel (refereegranskat)abstract Existing epidemiological evidence regarding the potential role of (poly)phenol intake in prostate cancer (PCa) risk is scarce and, in the case of flavonoids, it has been suggested that their intake may increase PCa risk. We investigated the associations between the intake of the total and individual classes and subclasses of (poly)phenols and the risk of PCa, including clinically relevant subtypes. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort included 131,425 adult men from seven European countries. (Poly)phenol intake at baseline was assessed by combining validated center/country-specific dietary questionnaires and the Phenol-Explorer database. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). In total, 6939 incident PCa cases (including 3501 low-grade and 710 high-grade, 2446 localized and 1268 advanced, and 914 fatal Pca cases) were identified during a mean follow-up of 14 years. No associations were observed between the total intake of (poly)phenols and the risk of PCa, either overall (HRlog2 = 0.99, 95% CI 0.94–1.04) or according to PCa subtype. Null associations were also found between all classes (phenolic acids, flavonoids, lignans, and stilbenes) and subclasses of (poly)phenol intake and the risk of PCa, overall and according to PCa subtype. The results of the current large prospective cohort study do not support any association between (poly)phenol intake and PCa incidence.
16.	Arevalo-Martinez, Marycarmen, et al. (författare) miR-126 contributes to the epigenetic signature of diabetic vascular smooth muscle and enhances antirestenosis effects of Kv1.3 blockers 2021 Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 53 Tidskriftsartikel (refereegranskat)abstract Objectives: Restenosis after vessel angioplasty due to dedifferentiation of the vascular smooth muscle cells (VSMCs) limits the success of surgical treatment of vascular occlusions. Type 2 diabetes (T2DM) has a major impact on restenosis, with patients exhibiting more aggressive forms of vascular disease and poorer outcomes after surgery. Kv1.3 channels are critical players in VSMC proliferation. Kv1.3 blockers inhibit VSMCs MEK/ERK signalling and prevent vessel restenosis. We hypothesize that dysregulation of microRNAs (miR) play critical roles in adverse remodelling, contributing to Kv1.3 blockers efficacy in T2DM VSMCs. Methods and results: We used clinically relevant in vivo models of vascular risk factors (VRF) and vessels and VSMCs from T2DM patients. Resukts: Human T2DM vessels showed increased remodelling, and changes persisted in culture, with augmented VSMCs migration and proliferation. Moreover, there were downregulation of PI3K/AKT/mTOR and upregulation of MEK/ERK pathways, with increased miR-126 expression. The inhibitory effects of Kv1.3 blockers on remodelling were significantly enhanced in T2DM VSMCs and in VRF model. Finally, miR-126 overexpression confered “diabetic” phenotype to non-T2DM VSMCs by downregulating PI3K/AKT axis. Conclusions: miR-126 plays crucial roles in T2DM VSMC metabolic memory through activation of MEK/ERK pathway, enhancing the efficacy of Kv1.3 blockers in the prevention of restenosis in T2DM patients.
17.	Arévalo-Martínez, Marycarmen, et al. (författare) Myocardin-Dependent Kv1.5 Channel Expression Prevents Phenotypic Modulation of Human Vessels in Organ Culture 2019 Ingår i: Arteriosclerosis, Thrombosis, and Vascular Biology. - 1524-4636. ; 39:12, s. 273-286 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: We have previously described that changes in the expression of Kv channels associate to phenotypic modulation (PM), so that Kv1.3/Kv1.5 ratio is a landmark of vascular smooth muscle cells phenotype. Moreover, we demonstrated that the Kv1.3 functional expression is relevant for PM in several types of vascular lesions. Here, we explore the efficacy of Kv1.3 inhibition for the prevention of remodeling in human vessels, and the mechanisms linking the switch in Kv1.3 /Kv1.5 ratio to PM. Approach and Results: Vascular remodeling was explored using organ culture and primary cultures of vascular smooth muscle cells obtained from human vessels. We studied the effects of Kv1.3 inhibition on serum-induced remodeling, as well as the impact of viral vector-mediated overexpression of Kv channels or myocardin knock-down. Kv1.3 blockade prevented remodeling by inhibiting proliferation, migration, and extracellular matrix secretion. PM activated Kv1.3 via downregulation of Kv1.5. Hence, both Kv1.3 blockers and Kv1.5 overexpression inhibited remodeling in a nonadditive fashion. Finally, myocardin knock-down induced vessel remodeling and Kv1.5 downregulation and myocardin overexpression increased Kv1.5, while Kv1.5 overexpression inhibited PM without changing myocardin expression. CONCLUSIONS: We demonstrate that Kv1.5 channel gene is a myocardin-regulated, vascular smooth muscle cells contractile marker. Kv1.5 downregulation upon PM leaves Kv1.3 as the dominant Kv1 channel expressed in dedifferentiated cells. We demonstrated that the inhibition of Kv1.3 channel function with selective blockers or by preventing Kv1.5 downregulation can represent an effective, novel strategy for the prevention of intimal hyperplasia and restenosis of the human vessels used for coronary angioplasty procedures.
18.	Askri, Dalel, et al. (författare) A blood test to monitor bee health across a European network of agricultural sites of different land-use by MALDI BeeTyping mass spectrometry 2024 Ingår i: Science of the Total Environment. - 0048-9697. ; 929 Tidskriftsartikel (refereegranskat)abstract There are substantial concerns about impaired honey bee health and colony losses due to several poorly understood factors. We used MALDI profiling (MALDI BeeTyping®) analysis to investigate how some environmental and management factors under field conditions across Europe affected the honey bee haemolymph peptidome (all peptides in the circulatory fluid), as a profile of molecular markers representing the immune status of Apis mellifera. Honey bees were exposed to a range of environmental stressors in 128 agricultural sites across eight European countries in four biogeographic zones, with each country contributing eight sites each for two different cropping systems: oilseed rape (OSR) and apple (APP). The full haemolymph peptide profiles, including the presence and levels of three key immunity markers, namely the antimicrobial peptides (AMPs) Apidaecin, Abaecin and Defensin-1, allowed the honey bee responses to environmental variables to be discriminated by country, crop type and site. When considering just the AMPs, it was not possible to distinguish between countries by the prevalence of each AMP in the samples. However, it was possible to discriminate between countries on the amounts of the AMPs, with the Swedish samples in particular expressing high amounts of all AMPs. A machine learning model was developed to discriminate the haemolymphs of bees from APP and OSR sites. The model was 90.6 % accurate in identifying the crop type from the samples used to build the model. Overall, MALDI BeeTyping® of bee haemolymph represents a promising and cost-effective “blood test” for simultaneously monitoring dozens of peptide markers affected by environmental stressors at the landscape scale, thus providing policymakers with new diagnostic and regulatory tools for monitoring bee health.
19.	Bisschops, Mark, 1985, et al. (författare) Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae 2015 Ingår i: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 2:11, s. 429-444 Tidskriftsartikel (refereegranskat)abstract Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of anaerobic batch cultures was already evident during the exponential growth phase and, in contrast to the situation in aerobic cultures, was not substantially increased during transition into SP. A combination of physiological and transcriptome analysis showed that the slow post-diauxic growth phase on ethanol, which precedes SP in aerobic, but not in anaerobic cultures, endowed cells with the time and resources needed for inducing longevity and thermotolerance. When combined with literature data on acquisition of longevity and thermotolerance in retentostat cultures, the present study indicates that the fast transition from glucose excess to SP in anaerobic cultures precludes acquisition of longevity and thermotolerance. Moreover, this study demonstrates the importance of a preceding, calorie-restricted conditioning phase in the acquisition of longevity and stress tolerance in SP yeast cultures, irrespective of oxygen availability.
20.	Blaksley, Carl, et al. (författare) Heavy neutrinos and lepton number violation in ℓp colliders 2011 Ingår i: Nuclear Physics B. - : Elsevier BV. - 0550-3213 .- 1873-1562. ; 852:2, s. 353-365 Tidskriftsartikel (refereegranskat)abstract We discuss the prospects of studying lepton number violating processes in order to identify Majorana neutrinos from low scale seesaw mechanisms at lepton-proton colliders. In particular, we consider the scenarios of colliding electrons with LHC energy protons and, motivated by the efforts towards the construction of a muon collider, the prospects of muon-proton collisions. We find that present constraints on the mixing of the Majorana neutrinos still allow for a detectable signal at these kind of facilities given the smallness of the Standard Model background. We discuss possible cuts in order to further increase the signal over background ratio and the prospects of reconstructing the neutrino mass from the kinematics of the final state particles.
21.	Blennow, Mattias, 1980-, et al. (författare) Non-unitarity, sterile neutrinos, and non-standard neutrino interactions 2017 Ingår i: Journal of High Energy Physics (JHEP). - : Springer. - 1126-6708 .- 1029-8479. ; :4 Tidskriftsartikel (refereegranskat)abstract The simplest Standard Model extension to explain neutrino masses involves the addition of right-handed neutrinos. At some level, this extension will impact neutrino oscillation searches. In this work we explore the differences and similarities between the case in which these neutrinos are kinematically accessible (sterile neutrinos) or not (mixing matrix non-unitarity). We clarify apparent inconsistencies in the present literature when using different parametrizations to describe these effects and recast both limits in the popular neutrino non-standard interaction (NSI) formalism. We find that, in the limit in which sterile oscillations are averaged out at the near detector, their effects at the far detector coincide with non-unitarity at leading order, even in presence of a matter potential. We also summarize the present bounds existing in both limits and compare them with the expected sensitivities of near-future facilities taking the DUNE proposal as a benchmark. We conclude that non-unitarity effects are too constrained to impact present or near future neutrino oscillation facilities but that sterile neutrinos can play an important role at long baseline experiments. The role of the near detector is also discussed in detail.
22.	Blennow, Mattias, et al. (författare) Reassessing the sensitivity to leptonic CP violation 2015 Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :3 Tidskriftsartikel (refereegranskat)abstract We address the validity of the usual procedure to determine the sensitivity of neutrino oscillation experiments to CP violation. An explicit calibration of the test statistic is performed through Monte Carlo simulations for several experimental setups. We find that significant deviations from a chi(2) distribution with one degree of freedom occur for experimental setups with low sensitivity to ffi. In particular, when the allowed region to which ffi is constrained at a given confidence level is comparable to the whole allowed range, the cyclic nature of the variable manifests and the premises of Wilk's theorem are violated. This leads to values of the test statistic significantly lower than a chi(2) distribution at that confidence level. On the other hand, for facilities which can place better constraints on ffi the cyclic nature of the variable is hidden and, as the potential of the facility improves, the values of the test statistics first become slightly higher than and then approach asymptotically a chi(2) distribution. The role of sign degeneracies is also discussed.
23.	Blennow, Mattias, 1980-, et al. (författare) Right-handed neutrinos and the CDF II anomaly 2022 Ingår i: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 106:7 Tidskriftsartikel (refereegranskat)abstract We point out that right-handed neutrinos can resolve the tension between the latest CDF II measurement of MW and the SM. Integrating out the new states yields a single d 1/4 6 operator, which translates into a nonunitary leptonic mixing matrix. This alters the extraction of GF from muon decay and increases the prediction for MW, in line with the CDF II result. We find that this explanation worsens the so-called Cabibbo anomaly, which could still be explained through the same d 1/4 6 operator if it is not generated by right-handed neutrinos. Exploiting the flavor dependence, a common explanation of both anomalies would a priori be possible, but is ruled out by weak universality constraints.
24.	Blennow, Mattias, et al. (författare) The MOMENT to search for CP violation 2016 Ingår i: Journal of High Energy Physics (JHEP). - : Springer. - 1126-6708 .- 1029-8479. ; :3 Tidskriftsartikel (refereegranskat)abstract In this letter, we analyze for the first time the physics reach in terms of sensitivity to leptonic CP violation of the proposed MuOn-decay MEdium baseline NeuTrino beam (MOMENT) experiment, a novel neutrino oscillation facility that would operate with neutrinos from muon decay. Apart from obtaining a sufficiently intense flux, the bottlenecks to the physics reach of this experiment will be achieving a high enough suppression of the atmospheric background and, particularly, attaining a sufficient level of charge identification. We thus present our results as a function of these two factors. As for the detector, we consider a very massive Gd-doped Water Cherenkov detector. We find that MOMENT will be competitive with other currently planned future oscillation experiments if a charge identification of at least 80 % can be achieved at the same time that the atmospheric background can be suppressed by at least a factor of ten. We also find a large synergy of MOMENT with the current generation of neutrino oscillation experiments, T2K and NOvA, which significantly enhances its final sensitivity.
25.	Bottero, Irene, et al. (författare) Impact of landscape configuration and composition on pollinator communities across different European biogeographic regions 2023 Ingår i: Frontiers in Ecology and Evolution. - 2296-701X. ; 11 Tidskriftsartikel (refereegranskat)abstract Introduction: Heterogeneity in composition and spatial configuration of landscape elements support diversity and abundance of flower-visiting insects, but this is likely dependent on taxonomic group, spatial scale, weather and climatic conditions, and is particularly impacted by agricultural intensification. Here, we analyzed the impacts of both aspects of landscape heterogeneity and the role of climatic and weather conditions on pollinating insect communities in two economically important mass-flowering crops across Europe. Methods: Using a standardized approach, we collected data on the abundance of five insect groups (honey bees, bumble bees, other bees, hover flies and butterflies) in eight oilseed rape and eight apple orchard sites (in crops and adjacent crop margins), across eight European countries (128 sites in total) encompassing four biogeographic regions, and quantified habitat heterogeneity by calculating relevant landscape metrics for composition (proportion and diversity of land-use types) and configuration (the aggregation and isolation of land-use patches). Results: We found that flower-visiting insects responded to landscape and climate parameters in taxon- and crop-specific ways. For example, landscape diversity was positively correlated with honey bee and solitary bee abundance in oilseed rape fields, and hover fly abundance in apple orchards. In apple sites, the total abundance of all pollinators, and particularly bumble bees and solitary bees, decreased with an increasing proportion of orchards in the surrounding landscape. In oilseed rape sites, less-intensively managed habitats (i.e., woodland, grassland, meadows, and hedgerows) positively influenced all pollinators, particularly bumble bees and butterflies. Additionally, our data showed that daily and annual temperature, as well as annual precipitation and precipitation seasonality, affects the abundance of flower-visiting insects, although, again, these impacts appeared to be taxon- or crop-specific. Discussion: Thus, in the context of global change, our findings emphasize the importance of understanding the role of taxon-specific responses to both changes in land use and climate, to ensure continued delivery of pollination services to pollinator-dependent crops.
26.	Chajes, Veronique, et al. (författare) Ecological-Level Associations Between Highly Processed Food Intakes and Plasma Phospholipid Elaidic Acid Concentrations: Results From a Cross-Sectional Study Within the European Prospective Investigation Into Cancer and Nutrition (EPIC) 2011 Ingår i: Nutrition and Cancer. - : Informa UK Limited. - 1532-7914 .- 0163-5581. ; 63:8, s. 1235-1250 Tidskriftsartikel (refereegranskat)abstract Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.
27.	Donat-Vargas, C, et al. (författare) Olive oil consumption is associated with a lower risk of cardiovascular disease and stroke 2022 Ingår i: Clinical nutrition (Edinburgh, Scotland). - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 41:1, s. 122-130 Tidskriftsartikel (refereegranskat)
28.	Donat-Vargas, C, et al. (författare) Reply - Letter to the editor - Association between olive oil consumption and the risk of cardiovascular disease and stroke YCLNU-D-21-02208 2022 Ingår i: Clinical nutrition (Edinburgh, Scotland). - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 41:3, s. 784-785 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
29.	Dulsat-Masvidal, Maria, et al. (författare) A review of constraints and solutions for collecting raptor samples and contextual data for a European Raptor Biomonitoring Facility 2021 Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 793, s. 148599-148599 Tidskriftsartikel (refereegranskat)
30.	Ferrando, Carlos, et al. (författare) Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV) : a multicentre, randomised, controlled clinical trial 2024 Ingår i: The Lancet Respiratory Medicine. - : Elsevier. - 2213-2600 .- 2213-2619. ; 12:3, s. 195-206 Tidskriftsartikel (refereegranskat)abstract Background It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. Methods This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age >= 18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lungprotective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. Findings Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0 center dot 39 [95% CI 0 center dot 28 to 0 center dot 56]), with an absolute risk difference of -9 center dot 23 (95% CI -12 center dot 55 to -5 center dot 92). Recruitment manoeuvre-related adverse events were reported in five patients. Interpretation Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. Funding Instituto de Salud Carlos III and the European Regional Development Funds. Copyright (c) 2023 Elsevier Ltd. All rights reserved.
31.	Galar, Diego, et al. (författare) Cálculo de la vida útil remanente mediante trayectorias móviles entre hiperplanos de máquinas de de soporte vectorial : [Rul prediction using moving trajectories between svm hyper planes] 2013 Ingår i: Interciencia. - 0378-1844. ; 38:8, s. 556-562 Tidskriftsartikel (refereegranskat)abstract Se propone un nuevo método de predicción de vida útil remanente (RUL) inspirado en clasificadores de máquinas de soporte vectorial (SVM). Los datos históricos de condición de un sistema durante su tiempo de vida se utilizan para crear una clasificación mediante hiperplanos en SVM. Para estimar la RUL de un sistema, la velocidad de degradación se evalúa calculando la distancia mínima definida con base en las trayectorias de degradación; es decir, el acercamiento del sistema al hiperplano que segrega información de las condiciones buenas y malas en diferentes horizontes de tiempo. Se puede estimar la vida final de un componente específico, o la información de la RUL de una población ser calculada, mediante la agregación de múltiples estimaciones RUL usando un método de estimación de densidad. La degradación de un sistema se ve afectado por muchos factores desconocidos que, además de complicar los comportamientos de degradación, dificultan la recolección de datos con calidad. Debido a falta de conocimiento y medidas incompletas, normalmente se carece de información importante del contexto de los datos recogidos. Por ello se agrupan datos históricos del sistema con gran variedad de patrones de degradación, con los que la búsqueda de un modelo global depredicción RUL es extremadamente difícil. Esto lleva a buscar técnicas avanzadas de predicción más allá de los modelos tradicionales. El modelo propuesto desarrolla un método eficaz de predicción RUL que aborda múltiples retos en pronósticos de sistemas complejos. Las similitudes entre trayectorias de degradación pueden contrastarse para enriquecer las metodologías actuales de prognosis. Para verificar el modelo se emplean datos del monitorizado de condición en rodamientos.
32.	Hernández-Breijo, Borja, et al. (författare) BAFF predicts immunogenicity in older patients with rheumatoid arthritis treated with TNF inhibitors 2021 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum B-cell activating factor (BAFF) with immunogenicity after 6 months of TNFi treatment. A total of 127 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association. At 6 months, 31 patients (24%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value = 5.30; p = 0.02); therefore, subsequent results were stratified according to mean age (≤ / > 55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR = 1.51; 95% CI 1.03-2.21). Baseline serum BAFF ≥ 1034 pg/mL predicted the presence of ADA at 6 months (AUC = 0.81; 95% confidence interval (CI) 0.69-0.93; p = 0.001; positive likelihood ratio = 3.7). In conclusion, our results suggest that the association of BAFF concentration and immunogenicity depends on the patient's age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.
33.	Hodge, Simon, et al. (författare) Design and Planning of a Transdisciplinary Investigation into Farmland Pollinators : Rationale, Co-Design, and Lessons Learned 2022 Ingår i: Sustainability (Switzerland). - : MDPI AG. - 2071-1050. ; 14:17 Tidskriftsartikel (refereegranskat)abstract To provide a complete portrayal of the multiple factors negatively impacting insects in agricultural landscapes it is necessary to assess the concurrent incidence, magnitude, and interactions among multiple stressors over substantial biogeographical scales. Trans-national ecological field investigations with wide-ranging stakeholders typically encounter numerous challenges during the design planning stages, not least that the scientific soundness of a spatially replicated study design must account for the substantial geographic and climatic variation among distant sites. ‘PoshBee’ (Pan-European assessment, monitoring, and mitigation of Stressors on the Health of Bees) is a multi-partner transdisciplinary agroecological project established to investigate the suite of stressors typically encountered by pollinating insects in European agricultural landscapes. To do this, PoshBee established a network of 128 study sites across eight European countries and collected over 50 measurements and samples relating to the nutritional, toxicological, pathogenic, and landscape components of the bees’ environment. This paper describes the development process, rationale, and end-result of each aspect of the of the PoshBee field investigation. We describe the main issues and challenges encountered during the design stages and highlight a number of actions or processes that may benefit other multi-partner research consortia planning similar large-scale studies. It was soon identified that in a multi-component study design process, the development of interaction and communication networks involving all collaborators and stakeholders requires considerable time and resources. It was also necessary at each planning stage to be mindful of the needs and objectives of all stakeholders and partners, and further challenges inevitably arose when practical limitations, such as time restrictions and labour constraints, were superimposed upon prototype study designs. To promote clarity for all stakeholders, for each sub-component of the study, there should be a clear record of the rationale and reasoning that outlines how the final design transpired, what compromises were made, and how the requirements of different stakeholders were accomplished. Ultimately, multi-national agroecological field studies such as PoshBee benefit greatly from the involvement of diverse stakeholders and partners, ranging from field ecologists, project managers, policy legislators, mathematical modelers, and farmer organisations. While the execution of the study highlighted the advantages and benefits of large-scale transdisciplinary projects, the long planning period emphasized the need to formally describe a design framework that could facilitate the design process of future multi-partner collaborations.
34.	Hurtado, Pilar, et al. (författare) Contrasting Environmental Drivers Determine Biodiversity Patterns in Epiphytic Lichen Communities along a European Gradient 2020 Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 8:12 Tidskriftsartikel (refereegranskat)abstract Assessing the ecological impacts of environmental change on biological communities requires knowledge of the factors driving the spatial patterns of the three diversity facets along extensive environmental gradients. We quantified the taxonomic (TD), functional (FD), and phylogenetic diversity (PD) of lichen epiphytic communities in 23 beech forests along Europe to examine their response to environmental variation (climate, habitat quality, spatial predictors) at a continental geographic scale. We selected six traits related to the climatic conditions in forest ecosystems, the water-use strategy and the nutrient uptake, and we built a phylogenetic tree based on four molecular markers. FD and climate determined TD and PD, with spatial variables also affecting PD. The three diversity facets were primarily shaped by distinct critical predictors, with the temperature diurnal range affecting FD and PD, and precipitation of the wettest month determining TD. Our results emphasize the value of FD for explaining part of TD and PD variation in lichen communities at a broad geographic scale, while highlighting that these diversity facets provide complementary information about the communities' response under changing environmental conditions. Furthermore, traits such as growth form, photobiont type, and reproductive strategy mediated the response of lichen communities to abiotic factors emerging as useful indicators of macroclimatic variations.
35.	Håkansson, Gisela, et al. (författare) Processability theory : explaining developmental sequences 2013 Ingår i: Contemporary Approaches to Second Language Acquisition. - Amsterdam : John Benjamins Publishing Company. - 1875-1113. - 9789027205254 - 9789027205285 - 9789027272225 ; 9, s. 111-128 Bokkapitel (refereegranskat)abstract This chapter presents a psycholinguistic account of the developmental sequences found in second language acquisition (SLA). Building on Levelt’s (1989) model of speech production, Processability Theory (PT: Pienemann 1998, 2005) proposes that the order in which morpho-syntactic structures are acquired will be controlled by the processing requirements of those structures. The cross- linguistic validity of PT will be illustrated by the analysis of learner data in some typologically diverse languages. The findings show that the hierarchical sequence of processing procedures is similar across languages, if the emergence criterion is used, and also that the influence of any previously acquired language is constrained by the processability of the structures. The implications of these findings for SLA research and profiling will be discussed.
36.	Iregren, Elisabeth, et al. (författare) Dieta y Crecimiento Infantil Medieval en una Sociedad Rural del Norte de Europa 2016 Ingår i: Poblaciones Humanas, Genética, Ambiente y Alimentación. - 9788461752997 ; , s. 391-406 Konferensbidrag (refereegranskat)abstract ABSTRACT Introduction: Scientists from many disciplines have studied population, church and burials from the Early Medieval churchyard Västerhus/Westerhus in Middle Sweden. Archaeology, anthropology, odontology and demography of this population have been investigated. The present project group has, above all, investigated teeth, bones and bone chemistry. But also many archaeological questions have been enlightened during the work. Methods: In this contribution, we penetrate the diet of the children through investigations of the trace element Strontium and of Nitrogen isotopes, which have been used to map breast-feeding as well as diet during later child-hood. Results: Most children have been wet-nursed up to the age of 1.5-2 years. From the age of about 5 years, the children consumed similar food as the adults. It seems as if most children, regardless of family relation, were breastfed by women 391 XIX Congreso de la Sociedad Española de Antropología Física working at the manor. Bone elements from all body parts of the children have been measured meticulously. In this article we have focused on growth of the skeletal elements from the lower extremity. Teeth have also been measured and used for age determination. Occurrence of cribra orbitalia and enamel hypoplasia has, further, been registered. Conclusions: We demonstrate how bone size of the leg related to age has been influenced by nutrition and disease as expressed by occurrence of cribra orbitalia. Keywords: Medieval churchyard, children, diet, growth. RESUMEN Introducción: Científicos de diferentes disciplinas han estudiado la población medieval de la Baja Edad Media a partir de las tumbas y el cementerio de la iglesia de Västerhus/Westerhus (Suecia central). Utilizando estos restos se ha estudido la arqueología, antropología, odontología y demografía de esta población. En esta investigación se estudiaron sobre todo dientes, huesos y composición química de los mismos, pero también se elucidaron muchas cuestiones arqueológicas durante el trabajo. Metodología: Para esta comunicación, se investigó sobre la alimentación infantil a través de elementos traza de Estroncio e isotopos de Nitrógeno, que fueron utilizados para describir los patrones de lactancia así como la alimentación en la niñez. Resultados: La mayoría de los niños y niñas fueron amamantados hasta los 1.5- 2 años de edad. Desde los 5 años aproximadamente los niños tenían una alimentación similar a la de los adultos. Parece ser que la mayoría de los niños, eran amamantados por mujeres que trabajaban en el señorío, independientemente de la relación familiar. Se midieron meticulosamente los huesos de niños de todas las partes del cuerpo. En esta comunicación nos centraremos en elementos óseos de la extremidad inferior. Los dientes fueron medidos y utilizados para la determinación de la edad. Se registró también la presencia de cribra orbitalia y de hipoplasia del esmalte. Conclusiones: Se observó relación entre la longitud del hueso de la pierna por edad y nutrition y enfermedad, mediante la presencia de cribra orbitalia. Palabras clave: cementerio medieval, niños, alimentación, crecimiento.
37.	Jenab, Mazda, et al. (författare) Consumption and portion sizes of tree nuts, peanuts and seeds in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries 2006 Ingår i: British Journal of Nutrition. - Cambridge : Cambridge University Press. - 1475-2662 .- 0007-1145. ; 96:1, s. 12-23 Tidskriftsartikel (refereegranskat)abstract Tree nuts, peanuts and seeds are nutrient dense foods whose intake has been shown to be associated with reduced risk of some chronic diseases. They are regularly consumed in European diets either as whole, in spreads or from hidden sources (e.g. commercial products). However, little is known about their intake profiles or differences in consumption between European countries or geographic regions. The objective of this study was to analyse the population mean intake and average portion sizes in subjects reporting intake of nuts and seeds consumed as whole, derived from hidden sources or from spreads. Data was obtained from standardised 24-hour dietary recalls collected from 36 994 subjects in 10 different countries that are part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Overall, for nuts and seeds consumed as whole, the percentage of subjects reporting intake on the day of the recall was: tree nuts=4 center dot 4%, peanuts=2 center dot 3 % and seeds=1 center dot 3 %. The data show a clear northern (Sweden: mean intake=0 center dot 15 g/d, average portion size=15 center dot 1 g/d) to southern (Spain: mean intake=2 center dot 99 g/d, average portion size=34 center dot 7 g/d) European gradient of whole tree nut intake. The three most popular tree nuts were walnuts, almonds and hazelnuts, respectively. In general, tree nuts were more widely consumed than peanuts or seeds. In subjects reporting intake, men consumed a significantly higher average portion size of tree nuts (28 center dot 5 v. 23 center dot 1 g/d, P < 0 center dot 01) and peanuts (46 center dot 1 v. 35 center dot 1 g/d, P < 0 center dot 01) per day than women. These data may be useful in devising research initiatives and health policy strategies based on the intake of this food group.
38.	Lahmann, Petra H, et al. (författare) Body size and breast cancer risk : findings from the European Prospective Investigation into Cancer And Nutrition (EPIC). 2004 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 111:5, s. 762-71 Tidskriftsartikel (refereegranskat)
39.	Lahmann, Petra H, et al. (författare) Physical Activity and Breast Cancer Risk: The European Prospective Investigation into Cancer and Nutrition. 2007 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:1, s. 36-42 Tidskriftsartikel (refereegranskat)abstract There is convincing evidence for a decreased risk of breast cancer with increased physical activity. Uncertainties remain, however, about the role of different types of physical activity on breast cancer risk and the potential effect modification for these associations. We used data from 218,169 premenopausal and postmenopausal women from nine European countries, ages 20 to 80 years at study entry into the European Prospective Investigation into Cancer and Nutrition. Hazard ratios (HR) from multivariate Cox regression models were calculated using metabolic equivalent value-based physical activity variables categorized in quartiles, adjusted for age, study center, education, body mass index, smoking, alcohol use, age at menarche, age at first pregnancy, parity, current oral contraceptive use, and hormone replacement therapy use. The physical activity assessment included recreational, household, and occupational activities. A total physical activity index was estimated based on cross-tabulation of these separate types of activity. During 6.4 years of follow-up, 3,423 incident invasive breast cancers were identified. Overall, increasing total physical activity was associated with a reduction in breast cancer risk among postmenopausal women (P-trend = 0.06). Specifically, household activity was associated with a significantly reduced risk in postmenopausal (HR, 0.81; 95% confidence interval, 0.70-0.93, highest versus the lowest quartile; P-trend = 0.001) and premenopausal (HR, 0.71; 95% confidence interval, 0.55-0.90, highest versus lowest quartile; P-trend = 0.003) women. Occupational activity and recreational activity were not significantly related to breast cancer risk in both premenopausal and postmenopausal women. This study provides additional evidence for a protective effect of physical activity on breast cancer risk.
40.	LAURENT, Marion, et al. (författare) Novel indices reveal that pollinator exposure to pesticides varies across biological compartments and crop surroundings 2024 Ingår i: Science of the Total Environment. - 0048-9697. ; 927 Tidskriftsartikel (refereegranskat)abstract Declines in insect pollinators have been linked to a range of causative factors such as disease, loss of habitats, the quality and availability of food, and exposure to pesticides. Here, we analysed an extensive dataset generated from pesticide screening of foraging insects, pollen-nectar stores/beebread, pollen and ingested nectar across three species of bees collected at 128 European sites set in two types of crop. In this paper, we aimed to (i) derive a new index to summarise key aspects of complex pesticide exposure data and (ii) understand the links between pesticide exposures depicted by the different matrices, bee species and apple orchards versus oilseed rape crops. We found that summary indices were highly correlated with the number of pesticides detected in the related matrix but not with which pesticides were present. Matrices collected from apple orchards generally contained a higher number of pesticides (7.6 pesticides per site) than matrices from sites collected from oilseed rape crops (3.5 pesticides), with fungicides being highly represented in apple crops. A greater number of pesticides were found in pollen-nectar stores/beebread and pollen matrices compared with nectar and bee body matrices. Our results show that for a complete assessment of pollinator pesticide exposure, it is necessary to consider several different exposure routes and multiple species of bees across different agricultural systems.
41.	Linseisen, Jakob, et al. (författare) Fruit and vegetable consumption and lung cancer risk: Updated information from the European Prospective Investigation into Cancer and Nutrition (EPIC) 2007 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:5, s. 1103-1114 Tidskriftsartikel (refereegranskat)abstract The association of fruit and vegetable consumption and lung cancer incidence was evaluated using the most recent data from the European Prospective Investigation into Cancer and Nutrition (EPIC), applying a refined statistical approach (calibration) to account for measurement error potentially introduced by using food frequency questionnaire data. Between 1992 and 2000, detailed information on diet and life-style of 478,590 individuals participating in EPIC was collected. During a median follow-up of 6.4 years, 1,126 lung cancer cases were observed. Multivariate Cox proportional hazard models were applied for statistical evaluation. In the whole study population, fruit consumption was significantly inversely associated with lung cancer risk while no association was found for vegetable consumption. In current smokers, however, lung cancer risk significantly decreased with higher vegetable consumption; this association became more pronounced after calibration, the hazard ratio (HR) being 0.78 (95% CI 0.620.98) per 100 g increase in daily vegetable consumption. In comparison, the HR per 100 g fruit was 0.92 (0.85-0.99) in the entire cohort and 0.90 (0.81-0.99) in smokers. Exclusion of cases diagnosed during the first 2 years of follow-up strengthened these associations, the HR being 0.71 (0.55-0.94) for vegetables (smokers) and 0.86 (0.78-0.95) for fruit (entire cohort). Cancer incidence decreased with higher consumption of apples and pears (entire cohort) as well as root vegetables (smokers). In addition to an overall inverse association with fruit intake, the results of this evaluation add evidence for a significant inverse association of vegetable consumption and lung cancer incidence in smokers. (C) 2007 Wiley-Liss, Inc.
42.	Loureiro, Teresa, et al. (författare) Non-viable cervico-isthmic pregnancy: the importance of an accurate sonographic diagnosis to preserve fertility 2003 Ingår i: Fetal Diagnosis and Therapy. - : S. Karger AG. - 1015-3837 .- 1421-9964. ; 18:5, s. 289-291 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Cervico-isthmic pregnancy is a rare occurrence and until the use of current ultrasonographic techniques was associated with a disastrous outcome for women desiring to maintain their fertility. CASE REPORT: A 39-year-old woman was diagnosed at 12 weeks of amenorrhoea with an intra-uterine non-viable pregnancy and a low implantation of the gestational sac. Medical management of this situation with a regimen of intravaginal misoprostol was unsuccessful. At introduction of a cervical expander severe vaginal bleeding ensued, leading to an emergency curettage followed by a life-saving hysterectomy. Pathologic examination confirmed the peroperative impression of an isthmic implantation of the gestational sac. CONCLUSION: Early ultrasonographic diagnosis is essential to make conservative management of cervico-isthmic pregnancy possible.
43.	Martínez-Carranza, Markel, 1992-, et al. (författare) Synaptotagmin Binding to Botulinum Neurotoxins 2020 Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 59:4, s. 491-498 Tidskriftsartikel (refereegranskat)abstract Botulinum neurotoxins (BoNTs) are exceptionally toxic proteins that cause paralysis but are also extensively used as treatment for various medical conditions. Most BoNTs bind two receptors on neuronal cells, namely, a ganglioside and a protein receptor. Differences in the sequence between the protein receptors from different species can impact the binding affinity and toxicity of the BoNTs. Here we have investigated how BoNT/B, /DC, and /G, all three toxins that utilize synaptotagmin I and II (Syt-I and Syt-II, respectively) as their protein receptors, bind to Syt-I and -II of mouse/rat, bovine, and human origin by isothermal titration calorimetry analysis. BoNT/G had the highest affinity for human Syt-I, and BoNT/DC had the highest affinity for bovine Syt-II. As expected, BoNT/B, /DC, and /G showed very low levels of binding to human Syt-II. Furthermore, we carried out saturation transfer difference (STD) and STD-TOCSY NMR experiments that revealed the region of the Syt peptide in direct contact with BoNT/G, which demonstrate that BoNT/G recognizes the Syt peptide in a model similar to that in the established BoNT/B-Syt-II complex. Our analyses also revealed that regions outside the Syt peptide’s toxin-binding region are important for the helicity of the peptide and, therefore, the binding affinity.
44.	Martínez, Eriel, et al. (författare) Biochemical characterization of the oxygenation of unsaturated fatty acids by the dioxygenase and hydroperoxide isomerase of Pseudomonas aeruginosa 42A2 2010 Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:13, s. 9339-9345 Tidskriftsartikel (refereegranskat)abstract We have studied oxygenation of fatty acids by cell extract of Pseudomonas aeruginosa 42A2. Oleic acid ((9Z)-18:1) was transformed to (10S)-hydroperoxy-(8E)-octadecenoic acid ((10S)-HPOME) and to (7S,10S)-dihydroxy-(8E)-octadecenoic acid (7,10-DiHOME). Experiments under oxygen-18 showed that 7,10-DiHOME contained oxygen from air and was formed sequentially from (10S)-HPOME by isomerization. (10R)-HPOME was not isomerized. The (10S)-dioxygenase and hydroperoxide isomerase activities co-eluted on ion exchange chromatography and on gel filtration with an apparent molecular size of approximately 50 kDa. 16:1n-7, 18:2n-6, and 20:1n-11 were also oxygenated to 7,10-dihydroxy fatty acids, and (8Z)-18:1 was oxygenated to 6,9-dihydroxy-(7E)-octadecenoic acid. A series of fatty acids with the double bond positioned closer to ((6Z)-18:1, (5Z,9Z)-18:2) or more distant from the carboxyl group ((11Z)-, (13Z)-, and (15Z)-18:1) were poor substrates. The oxygenation mechanism was studied with [7S-(2)H]18:1n-9, [7R-(2)H]18:2n-6, and [8R-(2)H]18:2n-6 as substrates. The pro-R hydrogen at C-8 was lost in the biosynthesis of (10S)-HPODE, whereas the pro-S hydrogen was lost and the pro-R hydrogen was retained at C-7 during biosynthesis of the 7,10-dihydroxy metabolites. Analysis of the fatty acid composition of P. aeruginosa revealed relatively large amounts of (9E/Z)-16:1 and (11E/Z)-18:1 and only traces of 18:1n-9. We found that (11Z)-18:1 (vaccenic acid) was transformed to (11S,14S)-dihydroxy-(12E)-octadecenoic acid and to a mixture of 11- and 12-HPOME, possibly due to reverse orientation of (11Z)-18:1 at the active site compared with oleic acid. The reaction mechanism of the hydroperoxide isomerase suggests catalytic similarities to cytochrome P450.
45.	Martínez-Hidalgo, Pilar, et al. (författare) Medicago root nodule microbiomes: insights into a complex ecosystem with potential candidates for plant growth promotion 2021 Ingår i: Plant and Soil. - : Springer. - 0032-079X .- 1573-5036. Tidskriftsartikel (refereegranskat)abstract Purpose: Studying the legume nodule microbiome is important for understanding the development and nutrition of the plants inhabited by the various microbes within and upon them. We analyzed the microbiomes of these underground organs from both an important crop plant (Medicago sativa) and a related legume (M. polymorpha) using metagenomic and culture-based techniques to identify the main cultivatable contributors to plant growth enhancement.Methods: Using high-throughput sequencing, culturing, and in planta techniques, we identified and analyzed a broad population of the bacterial taxa within Medicago nodules and the surrounding soil.Results: Fifty-one distinct bacterial strains were isolated and characterized from nodules of both Medicago species and their growth-promoting activities were studied. Sequencing of 16S rRNA gene amplicons showed that in addition to Ensifer, the dominant genus, a large number of Gram-positive bacteria belonging to the Firmicutes and Actinobacteria were also present. After performing ecological and plant growth-promoting trait analyses, selecting the most promising strains, and then performing in planta assays, we found that strains of Bacillus and Micromonospora among others could play important roles in supporting the growth, health, and productivity of the host plant.Conclusion: To our knowledge, the comparison of the biodiversity of the microbiota of undomesticated vs. cultivated Medicago roots and nodules is novel and shows the range of potential Plant Growth-Promoting Bacteria that could be used for plants of agricultural interest. These and other nodule-isolated microbes could also serve as inoculants with rhizobia with the goal of replacing synthetic fertilizers and pesticides for sustainable agriculture.
46.	Matabuena, Marcos, et al. (författare) Identification of Asthma Phenotypes in the Spanish MEGA Cohort Study Using Cluster Analysis 2023 Ingår i: Archivos de Bronconeumologia. - : Elsevier BV. - 0300-2896. ; 59:4, s. 223-231 Tidskriftsartikel (refereegranskat)abstract Introduction: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes. Methods: We performed a multicentre prospective cohort study, including adult patients with asthma (N = 512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm. Results: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities. Conclusion: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps.
47.	McKay, James D., et al. (författare) A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium 2011 Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3 Tidskriftsartikel (refereegranskat)abstract Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
48.	Middha, Pooja K., et al. (författare) A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry 2023 Ingår i: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1 Tidskriftsartikel (refereegranskat)abstract Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
49.	Movalli, Paola, et al. (författare) Progress on bringing together raptor collections in Europe for contaminant research and monitoring in relation to chemicals regulation 2019 Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 26, s. 20132-20136 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
50.	Nicholson, Charlie C, et al. (författare) Pesticide use negatively affects bumble bees across European landscapes 2024 Ingår i: Nature. - 0028-0836 .- 1476-4687. Tidskriftsartikel (refereegranskat)abstract Sustainable agriculture requires balancing crop yields with the effects of pesticides on non-target organisms, such as bees and other crop pollinators. Field studies demonstrated that agricultural use of neonicotinoid insecticides can negatively affect wild bee species 1,2, leading to restrictions on these compounds 3. However, besides neonicotinoids, field-based evidence of the effects of landscape pesticide exposure on wild bees is lacking. Bees encounter many pesticides in agricultural landscapes 4-9 and the effects of this landscape exposure on colony growth and development of any bee species remains unknown. Here we show that the many pesticides found in bumble bee-collected pollen are associated with reduced colony performance during crop bloom, especially in simplified landscapes with intensive agricultural practices. Our results from 316 Bombus terrestris colonies at 106 agricultural sites across eight European countries confirm that the regulatory system fails to sufficiently prevent pesticide-related impacts on non-target organisms, even for a eusocial pollinator species in which colony size may buffer against such impacts 10,11. These findings support the need for postapproval monitoring of both pesticide exposure and effects to confirm that the regulatory process is sufficiently protective in limiting the collateral environmental damage of agricultural pesticide use.

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