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1.	Fox, Z, et al. (author) Predictors of CD4 count change over 8 months of follow up in HIV-1-infected patients with a CD4 count>or=300 cells/microL who were assigned to 7.5 MIU interleukin-2 2007 In: HIV medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 8:2, s. 112-123 Journal article (peer-reviewed)
2.	Kang, E. Y., et al. (author) CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study 2023 In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 129:5, s. 697-713 Journal article (peer-reviewed)abstract Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. Conclusion: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
3.	Kattge, Jens, et al. (author) TRY plant trait database - enhanced coverage and open access 2020 In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188 Journal article (peer-reviewed)abstract Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
4.	Loza, M. J., et al. (author) Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study 2016 In: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1 Journal article (peer-reviewed)abstract Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
5.	Dickson, EA, et al. (author) Carbon Dioxide Embolism Associated With Transanal Total Mesorectal Excision Surgery: A Report From the International Registries 2019 In: Diseases of the colon and rectum. - 1530-0358. ; 62:7, s. 794-801 Journal article (peer-reviewed)
6.	Werren, John H, et al. (author) Functional and evolutionary insights from the genomes of three parasitoid Nasonia species. 2010 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8 Journal article (peer-reviewed)abstract We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
7.	Jang, Seon-Kyeong, et al. (author) Rare genetic variants explain missing heritability in smoking. 2022 In: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 6:11, s. 1577-1586 Journal article (peer-reviewed)abstract Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.
8.	Kobel, M., et al. (author) p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study 2023 In: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 9:3, s. 208-222 Journal article (peer-reviewed)abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
9.	Tuson, A., et al. (author) TESS and CHEOPS discover two warm sub-Neptunes transiting the bright K-dwarf HD 15906 2023 In: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 3090-3118 Journal article (peer-reviewed)abstract We report the discovery of two warm sub-Neptunes transiting the bright (G = 9.5 mag) K-dwarf HD 15906 (TOI 461, TIC 4646810). This star was observed by the Transiting Exoplanet Survey Satellite (TESS) in sectors 4 and 31, revealing two small transiting planets. The inner planet, HD 15906 b, was detected with an unambiguous period but the outer planet, HD 15906 c, showed only two transits separated by ∼ 734 d, leading to 36 possible values of its period. We performed follow-up observations with the CHaracterising ExOPlanet Satellite (CHEOPS) to confirm the true period of HD 15906 c and improve the radius precision of the two planets. From TESS, CHEOPS, and additional ground-based photometry, we find that HD 15906 b has a radius of 2.24 ± 0.08 R and a period of 10.924709 ± 0.000032 d, whilst HD 15906 c has a radius of 2.93+−000607 R and a period of 21.583298+−00000055000052 d. Assuming zero bond albedo and full day-night heat redistribution, the inner and outer planet have equilibrium temperatures of 668 ± 13 K and 532 ± 10 K, respectively. The HD 15906 system has become one of only six multiplanet systems with two warm (700 K) sub-Neptune sized planets transiting a bright star (G ≤ 10 mag). It is an excellent target for detailed characterization studies to constrain the composition of sub-Neptune planets and test theories of planet formation and evolution.
10.	Li, J, et al. (author) Artemisinins Target GABAA Receptor Signaling and Impair α Cell Identity 2017 In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 168:1-2, s. 86- Journal article (peer-reviewed)
11.	Goni, Maria Fernanda Sanchez, et al. (author) The ACER pollen and charcoal database : a global resource to document vegetation and fire response to abrupt climate changes during the last glacial period 2017 In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 9:2, s. 679-695 Journal article (peer-reviewed)abstract Quaternary records provide an opportunity to examine the nature of the vegetation and fire responses to rapid past climate changes comparable in velocity and magnitude to those expected in the 21st-century. The best documented examples of rapid climate change in the past are the warming events associated with the Dansgaard-Oeschger (D-O) cycles during the last glacial period, which were sufficiently large to have had a potential feedback through changes in albedo and greenhouse gas emissions on climate. Previous reconstructions of vegetation and fire changes during the D-O cycles used independently constructed age models, making it difficult to compare the changes between different sites and regions. Here, we present the ACER (Abrupt Climate Changes and Environmental Responses) global database, which includes 93 pollen records from the last glacial period (73-15 ka) with a temporal resolution better than 1000 years, 32 of which also provide charcoal records. A harmonized and consistent chronology based on radiometric dating (C-14, U-234/Th-230, optically stimulated luminescence (OSL), Ar-40/Ar-39-dated tephra layers) has been constructed for 86 of these records, although in some cases additional information was derived using common control points based on event stratigraphy. The ACER database compiles metadata including geospatial and dating information, pollen and charcoal counts, and pollen percentages of the characteristic biomes and is archived in Microsoft Access (TM) at https://doi. org/10.1594/PANGAEA. 870867.
12.	Kato, Norihiro, et al. (author) Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation 2015 In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293 Journal article (peer-reviewed)abstract We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
13.	Sodergren, Erica, et al. (author) The genome of the sea urchin Strongylocentrotus purpuratus. 2006 In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52 Journal article (peer-reviewed)abstract We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
14.	Yates, James A. Fellows, et al. (author) The evolution and changing ecology of the African hominid oral microbiome 2021 In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 118:20 Journal article (peer-reviewed)abstract The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.
15.	Bansal, Sheel, et al. (author) Practical Guide to Measuring Wetland Carbon Pools and Fluxes 2023 In: Wetlands (Wilmington, N.C.). - : SPRINGER. - 0277-5212 .- 1943-6246. ; 43:8 Research review (peer-reviewed)abstract Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first define each of the major C pools and fluxes and provide rationale for their importance to wetland C dynamics. For each approach, we clarify what component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as where and when an approach is typically used, who can conduct the measurements (expertise, training requirements), and how approaches are conducted, including considerations on equipment complexity and costs. Finally, we review key covariates and ancillary measurements that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions.
16.	Hultström, Michael, 1978-, et al. (author) Commentaries on Viewpoint : Can elite athletes benefit from dietary nitrate supplementation? 2015 In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 119:6, s. 762-769 Journal article (peer-reviewed)
17.	Keir, AK, et al. (author) International, multicentre, observational study of fluid bolus therapy in neonates 2019 In: Journal of paediatrics and child health. - : Wiley. - 1440-1754 .- 1034-4810. ; 55:6, s. 632-639 Journal article (peer-reviewed)
18.	Liu, Ke, et al. (author) X Chromosome Dose and Sex Bias in Autoimmune Diseases 2016 In: Arthritis & Rheumatology. - : WILEY-BLACKWELL. - 2326-5191 .- 2326-5205. ; 68:5, s. 1290-1300 Journal article (peer-reviewed)abstract Objective. More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47, XXX; occurring in similar to 1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjogrens syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. Methods. All subjects in this study were female. We identified subjects with 47, XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47, XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. Results. We found 47, XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47, XXX. There was an excess of 47, XXX among SLE and SS patients. Conclusion. The estimated prevalence of SLE and SS in women with 47, XXX was similar to 2.5 and similar to 2.9 times higher, respectively, than that in women with 46, XX and similar to 25 and similar to 41 times higher, respectively, than that in men with 46, XY. No statistically significant increase of 47, XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.
19.	Liu, Ke, et al. (author) X Chromosome Dose and Sex Bias in Autoimmune Diseases : Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome 2016 In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:5, s. 1290-1300 Journal article (peer-reviewed)abstract OBJECTIVE:More than 80% of autoimmune disease is female dominant, but the mechanism for this female bias is poorly understood. We suspected an X chromosome dose effect and hypothesized that trisomy X (47,XXX, 1 in ∼1,000 live female births) would be increased in female predominant diseases (e.g. systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis [PBC] and rheumatoid arthritis [RA]) compared to diseases without female predominance (sarcoidosis) and controls.METHODS:We identified 47,XXX subjects using aggregate data from single nucleotide polymorphism (SNP) arrays and confirmed, when possible, by fluorescent in situ hybridization (FISH) or quantitative polymerase chain reaction (q-PCR).RESULTS:We found 47,XXX in seven of 2,826 SLE and three of 1,033 SS female patients, but only in two of the 7,074 female controls (p=0.003, OR=8.78, 95% CI: 1.67-86.79 and p=0.02, OR=10.29, 95% CI: 1.18-123.47; respectively). One 47,XXX subject was present for ∼404 SLE women and ∼344 SS women. 47,XXX was present in excess among SLE and SS subjects.CONCLUSION:The estimated prevalence of SLE and SS in women with 47,XXX was respectively ∼2.5 and ∼2.9 times higher than in 46,XX women and ∼25 and ∼41 times higher than in 46,XY men. No statistically significant increase of 47,XXX was observed in other female-biased diseases (PBC or RA), supporting the idea of multiple pathways to sex bias in autoimmunity. This article is protected by copyright. All rights reserved.
20.	Shraim, M. A., et al. (author) Features and methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system: a Delphi expert consensus study 2022 In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 163:9, s. 1812-1828 Journal article (peer-reviewed)abstract Classification of musculoskeletal pain based on underlying pain mechanisms (nociceptive, neuropathic, and nociplastic pain) is challenging. In the absence of a gold standard, verification of features that could aid in discrimination between these mechanisms in clinical practice and research depends on expert consensus. This Delphi expert consensus study aimed to: (1) identify features and assessment findings that are unique to a pain mechanism category or shared between no more than 2 categories and (2) develop a ranked list of candidate features that could potentially discriminate between pain mechanisms. A group of international experts were recruited based on their expertise in the field of pain. The Delphi process involved 2 rounds: round 1 assessed expert opinion on features that are unique to a pain mechanism category or shared between 2 (based on a 40% agreement threshold); and round 2 reviewed features that failed to reach consensus, evaluated additional features, and considered wording changes. Forty-nine international experts representing a wide range of disciplines participated. Consensus was reached for 196 of 292 features presented to the panel (clinical examination-134 features, quantitative sensory testing-34, imaging and diagnostic testing-14, and pain-type questionnaires-14). From the 196 features, consensus was reached for 76 features as unique to nociceptive (17), neuropathic (37), or nociplastic (22) pain mechanisms and 120 features as shared between pairs of pain mechanism categories (78 for neuropathic and nociplastic pain). This consensus study generated a list of potential candidate features that are likely to aid in discrimination between types of musculoskeletal pain.
21.	Cagnoli, Patricia C, et al. (author) Changes in Regional Brain Morphology in Neuropsychiatric Systemic Lupus Erythematosus. 2012 In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:5, s. 959-967 Journal article (peer-reviewed)abstract OBJECTIVE: Neuropsychiatric lupus (NPSLE) is a severe and potentially life-threatening condition, reported to occur in 25%-70% of patients with systemic lupus erythematosus (SLE). Brain imaging, especially magnetic resonance imaging, is frequently used to diagnose or exclude overt cerebral pathologies such as edema, hemorrhage, and central thrombosis. More advanced imaging techniques have been applied to demonstrate subtle changes in regional cerebral blood flow and brain structure. We investigated changes in regional gray-matter (GM) volume in SLE patients without neurological manifestations and NPSLE patients at an acute stage of the disease. METHODS: Using high-resolution structural images and voxel-based morphometry (VBM), we investigated regional GM volume in 20 NPSLE patients (within 2 weeks of the acute manifestation), 18 SLE patients without neurologic and/or psychiatric manifestations, and 18 healthy controls. RESULTS: VBM analyses revealed several regions of GM atrophy in various parts of the brain in NPSLE and SLE patients. GM atrophy was seen in both groups in the temporal and parietal lobes and was most pronounced in the posterior thalamus bilaterally. Both groups showed an increase in regional GM volume in the posterior parahippocampal gyrus. CONCLUSION: Our data suggest that changes in regional brain morphology are present in acute NPSLE, but also in SLE (as compared to controls), which might be indicative of a subclinical neurodegenerative process. Further research is needed to investigate whether specific neuropsychiatric symptoms are related to these changes.
22.	Cristea, A. Ioana, et al. (author) Approaches to Interdisciplinary Care for Infants with Severe Bronchopulmonary Dysplasia: A Survey of the Bronchopulmonary Dysplasia Collaborative 2022 In: American Journal of Perinatology. - : Georg Thieme Verlag KG. - 0735-1631 .- 1098-8785. Journal article (peer-reviewed)abstract Objective: Bronchopulmonary dysplasia (BPD) remains the most common late morbidity for extremely premature infants. Care of infants with BPD requires a longitudinal approach from the neonatal intensive care unit to ambulatory care though interdisciplinary programs. Current approaches for the development of optimal programs vary among centers.Study design: We conducted a survey of 18 academic centers that are members of the BPD Collaborative, a consortium of institutions with an established interdisciplinary BPD program. We aimed to characterize the approach, composition, and current practices of the interdisciplinary teams in inpatient and outpatient domains.Results: Variations exist among centers, including composition of the interdisciplinary team, whether the team is the primary or consult service, timing of the first team assessment of the patient, frequency and nature of rounds during the hospitalization, and the timing of ambulatory visits postdischarge.Conclusion: Further studies to assess long-term outcomes are needed to optimize interdisciplinary care of infants with severe BPD.Key points: · Care of infants with BPD requires a longitudinal approach from the NICU to ambulatory care.. · Benefits of interdisciplinary care for children have been observed in other chronic conditions.. · Current approaches for the development of optimal interdisciplinary BPD programs vary among centers..
23.	Demiris, G., et al. (author) Patient-centered Applications : Use of Information Technology to Promote Disease Management and Wellness. A White Paper by the AMIA Knowledge in Motion Working Group 2008 In: JAMIA Journal of the American Medical Informatics Association. - 1067-5027 .- 1527-974X. ; 15:1 Journal article (peer-reviewed)abstract Advances in information technology (IT) enable a fundamental redesign of health care processes based on the use and integration of electronic communication at all levels. New communication technologies can support a transition from institution centric to patient-centric applications. This white paper defines key principles and challenges for designers, policy makers, and evaluators of patient-centered technologies for disease management and prevention. It reviews current and emerging trends, highlights challenges related to design, evaluation, reimbursement and usability, and reaches conclusions for next steps that will advance the domain. © 2008 J Am Med Inform Assoc.
24.	Dorn, R. J., et al. (author) CRIRES+ on sky at the ESO Very Large Telescope : Observing the Universe at infrared wavelengths and high spectral resolution 2023 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671 Journal article (peer-reviewed)abstract The CRyogenic InfraRed Echelle Spectrograph (CRIRES) Upgrade project CRIRES+ extended the capabilities of CRIRES. It transformed this VLT instrument into a cross-dispersed spectrograph to increase the wavelength range that is covered simultaneously by up to a factor of ten. In addition, a new detector focal plane array of three Hawaii 2RG detectors with a 5.3 mu m cutoff wavelength replaced the existing detectors. Amongst many other improvements, a new spectropolarimetric unit was added and the calibration system has been enhanced. The instrument was installed at the VLT on Unit Telescope 3 at the beginning of 2020 and successfully commissioned and verified for science operations during 2021, partly remotely from Europe due to the COVID-19 pandemic. The instrument was subsequently offered to the community from October 2021 onwards. This article describes the performance and capabilities of the upgraded instrument and presents on sky results.
25.	Gentekaki, Eleni, et al. (author) Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis 2017 In: PLoS biology. - : PUBLIC LIBRARY SCIENCE. - 1544-9173 .- 1545-7885. ; 15:9 Journal article (peer-reviewed)abstract Blastocystis is the most prevalent eukaryotic microbe colonizing the human gut, infecting approximately 1 billion individuals worldwide. Although Blastocystis has been linked to intestinal disorders, its pathogenicity remains controversial because most carriers are asymptomatic. Here, the genome sequence of Blastocystis subtype (ST) 1 is presented and compared to previously published sequences for ST4 and ST7. Despite a conserved core of genes, there is unexpected diversity between these STs in terms of their genome sizes, guanine-cytosine (GC) content, intron numbers, and gene content. ST1 has 6,544 protein-coding genes, which is several hundred more than reported for ST4 and ST7. The percentage of proteins unique to each ST ranges from 6.2% to 20.5%, greatly exceeding the differences observed within parasite genera. Orthologous proteins also display extreme divergence in amino acid sequence identity between STs (i.e., 59%-61% median identity), on par with observations of the most distantly related species pairs of parasite genera. The STs also display substantial variation in gene family distributions and sizes, especially for protein kinase and protease gene families, which could reflect differences in virulence. It remains to be seen to what extent these inter-ST differences persist at the intra-ST level. A full 26% of genes in ST1 have stop codons that are created on the mRNA level by a novel polyadenylation mechanism found only in Blastocystis. Reconstructions of pathways and organellar systems revealed that ST1 has a relatively complete membrane-trafficking system and a near-complete meiotic toolkit, possibly indicating a sexual cycle. Unlike some intestinal protistan parasites, Blastocystis ST1 has near-complete de novo pyrimidine, purine, and thiamine biosynthesis pathways and is unique amongst studied stramenopiles in being able to metabolize alpha-glucans rather than beta-glucans. It lacks all genes encoding heme-containing cytochrome P450 proteins. Predictions of the mitochondrion-related organelle (MRO) proteome reveal an expanded repertoire of functions, including lipid, cofactor, and vitamin biosynthesis, as well as proteins that may be involved in regulating mitochondrial morphology and MRO/endoplasmic reticulum (ER) interactions. In sharp contrast, genes for peroxisome-associated functions are absent, suggesting Blastocystis STs lack this organelle. Overall, this study provides an important window into the biology of Blastocystis, showcasing significant differences between STs that can guide future experimental investigations into differences in their virulence and clarifying the roles of these organisms in gut health and disease.
26.	Groenewold, Nynke A., et al. (author) Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group 2023 In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:3, s. 1079-1089 Journal article (peer-reviewed)abstract There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
27.	Lozano, Manuel, et al. (author) Early life exposure to mercury and relationships with telomere length and mitochondrial DNA content in European children 2024 In: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 932 Journal article (peer-reviewed)abstract Background: Telomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation, respectively. Methylmercury (MeHg), a common pollutant in fish, induces oxidative stress. We hypothesized that elevated oxidative stress from exposure to MeHg decreases mtDNAcn and shortens TL. Methods: Study participants are 6–11-year-old children from the HELIX multi-center birth cohort study, comprising six European countries. Prenatal and postnatal total mercury (THg) concentrations were measured in blood samples, TL and mtDNAcn were determined in child DNA. Covariates and confounders were obtained by questionnaires. Robust regression models were run, considering sociodemographic and lifestyle covariates, as well as fish consumption. Sex, ethnicity, and fish consumption interaction models were also run. Results: We found longer TL with higher pre- and postnatal THg blood concentrations, even at low-level THg exposure according to the RfD proposed by the US EPA. The prenatal association showed a significant linear relationship with a 3.46 % increase in TL for each unit increased THg. The postnatal association followed an inverted U-shaped marginal non-linear relationship with 1.38 % an increase in TL for each unit increased THg until reaching a cut-point at 0.96 μg/L blood THg, from which TL attrition was observed. Higher pre- and postnatal blood THg concentrations were consistently related to longer TL among cohorts and no modification effect of fish consumption nor children's sex was observed. No association between THg exposure and mtDNAcn was found. Discussion: We found evidence that THg is associated with TL but the associations seem to be time- and concentration-dependent. Further studies are needed to clarify the mechanism behind the telomere changes of THg and related health effects.
28.	Mann, J., et al. (author) Complex terrain experiments in the New European Wind Atlas 2017 In: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 375:2091, s. 1-23 Journal article (peer-reviewed)abstract The New European Wind Atlas project will create a freely accessible wind atlas covering Europe and Turkey, develop the model chain to create the atlas and perform a series of experiments on flow in many different kinds of complex terrain to validate the models. This paper describes the experiments of which some are nearly completed while others are in the planning stage. All experiments focus on the flow properties that are relevant for wind turbines, so the main focus is the mean flow and the turbulence at heights between 40 and 300 m. Also extreme winds, wind shear and veer, and diurnal and seasonal variations of the wind are of interest. Common to all the experiments is the use of Doppler lidar systems to supplement and in some cases replace completely meteorological towers. Many of the lidars will be equipped with scan heads that will allow for arbitrary scan patterns by several synchronized systems. Two pilot experiments, one in Portugal and one in Germany, show the value of using multiple synchronized, scanning lidar, both in terms of the accuracy of the measurements and the atmospheric physical processes that can be studied. The experimental data will be used for validation of atmospheric flow models and will by the end of the project be freely available. This article is part of the themed issue 'Wind energy in complex terrains'.
29.	McKinney, Robin L, et al. (author) Ventilatory Strategies in Infants With Established Severe Bronchopulmonary Dysplasia : A Multicenter Point Prevalence Study. 2022 In: The Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 242, s. 248-252.e1 Journal article (peer-reviewed)abstract We performed a point prevalence study on infants with severe BPD collecting data on type and settings of ventilatory support; 187 infants were included from 15 centers, 51% who were on invasive positive pressure ventilation. We found significant center-specific variation in ventilator modes.
30.	Sangchooli, Arshiya, et al. (author) Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity 2024 In: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X. Research review (peer-reviewed)abstract Importance In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.
31.	Timmis, Kenneth, et al. (author) A concept for international societally relevant microbiology education and microbiology knowledge promulgation in society 2024 In: Microbial Biotechnology. - 1751-7907. ; 17:5 Journal article (peer-reviewed)abstract EXECUTIVE SUMMARY: Microbes are all pervasive in their distribution and influence on the functioning and well-being of humans, life in general and the planet. Microbially-based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision-makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative-the IMiLI-is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence-based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner-centric, not academic microbiology-centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators-learners. As such, they will collect and analyse feedback from the end-users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators-learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships-a global societally relevant microbiology education ecosystem-in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient.ABSTRACT: The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well-being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us-individuals/communities/nations/the human world-and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. HERE, WE PRESENT: our concept of how microbiology literacy may be achieved and the rationale underpinning it; the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision-making; and the key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner-centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091-1111). Importantly, although the primary target of the freely available (CC BY-NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity-driven, web-based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge.
32.	Wang, Page I., et al. (author) Perfusion-weighted MR Imaging in Cerebral Lupus Erythematosus 2012 In: Academic Radiology. - : Elsevier BV. - 1878-4046 .- 1076-6332. ; 19:8, s. 965-970 Journal article (peer-reviewed)abstract Rationale and Objective: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a diagnostically challenging, severe, and life-threatening condition, which is currently lacking a "gold standard." Our aim with this study is to look for magnetic resonance (MR) perfusion differences in NPSLE, SLE, and healthy control (HC) patients and correlate our findings with clinical parameters. Materials and Methods: Twenty-four NPSLE patients, 21 SLE patients, and 21 HC underwent dynamic susceptibility contrast enhanced MR perfusion using a 3-T scanner. Nine prospectively selected intracranial regions of interest were placed in white and gray matter and the cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MU) values were calculated. Subjects underwent clinical evaluation with SLEDAI and serum antibodies. Results: The SLE patients had higher CBF and CBV compared to the HC overall (P =.01) and in specific areas (P =.03-.048). SLE patients with signs of active disease (elevated SLEDAI and anti-double-stranded DNA) had significantly elevated CBV, CBF, and MU in the posterior cingulate gyrus (P =.01-.02). No significant difference was seen in the magnetic resonance perfusion measurements of NPSLE patients compared to SLE and HC, although the NPSLE patients also showed higher CBV variability compared to the SLE (P =.0004) and HC cohort (P <.0001). Conclusion: SLE patients have increased CBV and CBF compared to healthy controls. The SLE patients with clinical markers for active disease have elevated CBV, CBF, and MU in the posterior cingulate gyrus. NPSLE patients show increased variability in perfusion measurements, which may explain why susceptibility contrast enhanced MRI has not yet provided a specific target for NPSLE.
33.	Adrianto, Indra, et al. (author) Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus 2011 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:3, s. 253-258 Journal article (peer-reviewed)abstract Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 x 10(-8), odds ratio = 1.70) and Korean (P = 8.33 x 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-kappa B subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
34.	Albrecht, Daniel S., et al. (author) Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation 2019 In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 75, s. 72-83 Journal article (peer-reviewed)abstract Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C-11]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C-11]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C-11]PBR28 PET. 11 FM patients and 11 HC were scanned using [C-11]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (V-T) were computed from the [C-11]PBR28 data. [C-11]-L-deprenyl-D2 was quantified using lambda k(3). PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [C-11]PBR28 ITT and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [C-11]-L-deprenyl-Ds signal, including those demonstrating elevated [C-11] PBR28 signal in patients (p's >= 0.53, uncorrected). The elevations in [C-11]PBR28 V-T and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [C-11] PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [C-11]PBR28 signal were not also accompanied by increased [C-11]-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [C-11]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.
35.	Bjorkblom, Benny, et al. (author) c-Jun N-Terminal Kinase Phosphorylation of MARCKSL1 Determines Actin Stability and Migration in Neurons and in Cancer Cells 2012 In: Molecular and Cellular Biology. - 0270-7306. ; 32:17, s. 3513-3526 Journal article (peer-reviewed)abstract Cell migration is a fundamental biological function, critical during development and regeneration, whereas deregulated migration underlies neurological birth defects and cancer metastasis. MARCKS-like protein 1 (MARCKSL1) is widely expressed in nervous tissue, where, like Jun N-terminal protein kinase (JNK), it is required for neural tube formation, though the mechanism is unknown. Here we show that MARCKSL1 is directly phosphorylated by JNK on C-terminal residues (S120, T148, and T183). This phosphorylation enables MARCKSL1 to bundle and stabilize F-actin, increase filopodium numbers and dynamics, and retard migration in neurons. Conversely, when MARCKSL1 phosphorylation is inhibited, actin mobility increases and filopodium formation is compromised whereas lamellipodium formation is enhanced, as is cell migration. We find that MARCKSL1 mRNA is upregulated in a broad range of cancer types and that MARCKSL1 protein is strongly induced in primary prostate carcinomas. Gene knockdown in prostate cancer cells or in neurons reveals a critical role for MARCKSL1 in migration that is dependent on the phosphorylation state; phosphomimetic MARCKSL1 (MARCKSL1(S120D,T148D,T183D)) inhibits whereas dephospho-MARCKSL(1S120A,T148A,T183A) induces migration. In summary, these data show that JNK phosphorylation of MARCKSL1 regulates actin homeostasis, filopodium and lamellipodium formation, and neuronal migration under physiological conditions and that, when ectopically expressed in prostate cancer cells, MARCKSL1 again determines cell movement.
36.	Björkblom, Benny, et al. (author) All JNKs Can Kill, but Nuclear Localization Is Critical for Neuronal Death 2008 In: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 283:28, s. 19704-19713 Journal article (peer-reviewed)abstract JNKs are implicated in a range of brain pathologies and receive considerable attention as potential therapeutic targets. However, JNKs also regulate physiological and homeostatic processes. An attractive hypothesis from the drug development perspective is that distinct JNK isoforms mediate “physiological” and “pathological” responses. However, this lacks experimental evaluation. Here we investigate the isoforms, subcellular pools, and c-Jun/ATF2 targets of JNK in death of central nervous system neurons following withdrawal of trophic support. We use gene knockouts, gene silencing, subcellularly targeted dominant negative constructs, and pharmacological inhibitors. Combined small interfering RNA knockdown of all JNKs 1, 2, and 3, provides substantial neuroprotection. In contrast, knockdown or knock-out of individual JNKs or two JNKs together does not protect. This explains why the evidence for JNK in neuronal death has to date been largely pharmacological. Complete knockdown of c-Jun and ATF2 using small interfering RNA also fails to protect, casting doubt on c-Jun as a critical effector of JNK in neuronal death. Nonetheless, the death requires nuclear but not cytosolic JNK activity as nuclear dominant negative inhibitors of JNK protect, whereas cytosolic inhibitors only block physiological JNK function. Thus any one of the three JNKs is capable of mediating apoptosis and inhibition of nuclear JNK is protective.
37.	Björkblom, Benny, et al. (author) c-Jun N-Terminal Kinase Phosphorylation of MARCKSL1 Determines Actin Stability and Migration in Neurons and in Cancer Cells 2012 In: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 32:17, s. 3513-3526 Journal article (peer-reviewed)abstract Cell migration is a fundamental biological function, critical during development and regeneration, whereas deregulated migration underlies neurological birth defects and cancer metastasis. MARCKS-like protein 1 (MARCKSL1) is widely expressed in nervous tissue, where, like Jun N-terminal protein kinase (JNK), it is required for neural tube formation, though the mechanism is unknown. Here we show that MARCKSL1 is directly phosphorylated by JNK on C-terminal residues (S120, T148, and T183). This phosphorylation enables MARCKSL1 to bundle and stabilize F-actin, increase filopodium numbers and dynamics, and retard migration in neurons. Conversely, when MARCKSL1 phosphorylation is inhibited, actin mobility increases and filopodium formation is compromised whereas lamellipodium formation is enhanced, as is cell migration. We find that MARCKSL1 mRNA is upregulated in a broad range of cancer types and that MARCKSL1 protein is strongly induced in primary prostate carcinomas. Gene knockdown in prostate cancer cells or in neurons reveals a critical role for MARCKSL1 in migration that is dependent on the phosphorylation state; phosphomimetic MARCKSL1 (MARCKSL1S120D,T148D,T183D) inhibits whereas dephospho-MARCKSL1S120A,T148A,T183A induces migration. In summary, these data show that JNK phosphorylation of MARCKSL1 regulates actin homeostasis, filopodium and lamellipodium formation, and neuronal migration under physiological conditions and that, when ectopically expressed in prostate cancer cells, MARCKSL1 again determines cell movement.
38.	Boles, Oliver J. C., et al. (author) Historical Ecologies of Pastoralist Overgrazing in Kenya : Long-Term Perspectives on Cause and Effect 2019 In: Human Ecology. - : Springer Science and Business Media LLC. - 0300-7839 .- 1572-9915. ; 47:3, s. 419-434 Journal article (peer-reviewed)abstract The spectre of overgrazing' looms large in historical and political narratives of ecological degradation in savannah ecosystems. While pastoral exploitation is a conspicuous driver of landscape variability and modification, assumptions that such change is inevitable or necessarily negative deserve to be continuously evaluated and challenged. With reference to three case studies from Kenya - the Laikipia Plateau, the Lake Baringo basin, and the Amboseli ecosystem - we argue that the impacts of pastoralism are contingent on the diachronic interactions of locally specific environmental, political, and cultural conditions. The impacts of the compression of rangelands and restrictions on herd mobility driven by misguided conservation and economic policies are emphasised over outdated notions of pastoralist inefficiency. We review the application of overgrazing' in interpretations of the archaeological record and assess its relevance for how we interpret past socio-environmental dynamics. Any discussion of overgrazing, or any form of human-environment interaction, must acknowledge spatio-temporal context and account for historical variability in landscape ontogenies.
39.	Brewer, Courtney A., et al. (author) High spatial resolution full-field microscopy using a desktop-size soft x-ray laser 2007 In: Proceedings of SPIE. - : SPIE. Conference paper (peer-reviewed)abstract Images with nanoscale resolution were obtained in both transmission and reflection modes using a full-field microscope that is illuminated by an extremely compact λ = 46.9 nm (hv = 26.4 eV) soft x-ray laser. The microscope was used to image the surface of partially processed silicon semiconductor chips containing periodic patterns of polysilicon and metal lines. To characterize the microscope, modulation transfer functions were experimentally built for three different objective zone plates, and images with near-wavelength resolution were obtained.
40.	Brewer, Courtney A., et al. (author) Single-shot extreme ultraviolet laser imaging of nanostructures with wavelength resolution 2008 In: Optics Letters. - : Optical Society of America. - 0146-9592 .- 1539-4794. ; 33:5, s. 518-520 Journal article (peer-reviewed)abstract We have demonstrated near-wavelength resolution microscopy in the extreme ultraviolet. Images of 50 nm diameter nanotubes were obtained with a single ~1 ns duration pulse from a desktop-size 46.9 nm laser. We measured the modulation transfer function of the microscope for three different numerical aperture zone plate objectives, demonstrating that 54 nm half-period structures can be resolved. The combination of near-wavelength spatial resolution and high temporal resolution opens myriad opportunities in imaging, such as the ability to directly investigate dynamics of nanoscale structures.
41.	Brusaferri, Ludovica, et al. (author) Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset 2024 In: Brain, Behavior, and Immunity. - 0889-1591 .- 1090-2139. ; 116, s. 259-266 Journal article (peer-reviewed)abstract The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r's ≥ 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.
42.	Cagnoli, Patricia, et al. (author) Reduced Insular Glutamine and N-Acetylaspartate in Systemic Lupus Erythematosus: A Single-Voxel H-1-MR Spectroscopy Study 2013 In: Academic Radiology. - : Elsevier BV. - 1878-4046 .- 1076-6332. ; 20:10, s. 1286-1296 Journal article (peer-reviewed)abstract Rationale and Objectives: To investigate for differences in metabolic concentrations and ratios between patients with systemic lupus erythematosus (SLE) without (group SLE) and those with neurological symptoms (group NPSLE) compared to a healthy control (group HC) in three normal-appearing brain regions: the frontal white matter, right insula (RI), and occipital gray matter and whether changes in any of the metabolites or metabolic ratios are correlated to disease activity and other clinical parameters. Materials and Methods: Twenty patients with SLE (18 women and 2 men, age range 23.4-64.6 years, mean age 43.9 years), 23 NPSLE patients (23 women, age range 23.7-69.8 years, mean age 42.4 years), and 21 HC (19 women and 2 men, age range 21.0-65.7 years, mean age 43.4 years) were included. All subjects had conventional brain magnetic resonance imaging and H-1 single-voxel spectroscopy, clinical assessment, and laboratory testing. Results: NPSLE patients had significantly reduced N-acetylaspartate (NAA)/creatine compared to HC (P = .02) and SLE patients (P = .01) in the RI. Lower glutamine/creatine levels were also detected in RI in both patient groups and in frontal white matter in NPSLE patients compared to HC (P = .01, P = .02). NAA/Cr ratio in the RI was significantly negatively correlated with the Systemic Lupus Erythematosus Disease Activity Index (r = -0.41; P = .008), and patients with active SLE symptoms also had a trend toward lower NAA/creatine ratios (1.02 vs 1.12; P = .07). Conclusions: The present data support previous findings of abnormal metabolic changes in normal-appearing regions in the brain of both SLE and NPSLE patients and raise the possibility that especially NAA, glutamine, and glutamate may be additional biomarkers for cerebral disease activity in SLE patients as these early metabolic changes occur in the brain of SLE patients before neurologic and imaging manifestations become apparent.
43.	Carlbring, Per, et al. (author) On the Cusp of a 'New Era' : Integrating Technological Advances into Evidence-Based Assessment and Treatment 2018 Conference paper (other academic/artistic)abstract Approximately 1 in 5 adults in the U.S. experiences mental illness in a given year (NAMI). High-income nations spend on average 5 percent of total health spending on mental health, whereas low to middle-income countries spend less than 2 percent (WHO). Nearly nine in 10 Americans are online today, and more than three quarters of Americans own a smartphone. There are no differences in smartphone ownership among different racial and ethnic groups (Pew). Given this, advances in digital mental health applications provide new opportunities to increase access to traditionally underserved groups, customize interventions, and enhance our understanding of psychopathology on a large scale. This symposium showcases the use of digital health technologies in a variety of clinical samples and in the general population. We argue that the digital research laboratory extends far outside traditional brick-and-mortar labs. We will demonstrate that digital technologies provide benefit to patients/participants and generate scientific/clinical insights that would not have been possible with traditional models.Consistent with ABCT’s 2018 emphasis on technology, this set of speakers highlight perceptions, feasibility, acceptability, and importance of technological interventions. Additionally, our symposium is comprised of speakers at a range of career levels (including early and mid-career researchers, as well as a graduate student). First, Courtney Beard will present data on smartphone and social media usage in serious mental illness. Second, Marie Forgeard will present data from a smartphone self-assessment study in a partial hospital program. Third, Samantha Connolly will present data on veterans’ perceptions of smartphone app use in mental health care. Fourth, Chelsey Wilks will present data on “Pocket Skills”, a dialectical behavior therapy app for smartphones. Last, Lauren Rutter will introduce methods for building assessment tools for research that are designed with the goals of patients / participants in mind. Finally, Per Carlbringwill synthesize the talks and discuss the implications for research and clinical practice.
44.	Carleo, Ilaria, et al. (author) The Multiplanet System TOI-421* 2020 In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3 Journal article (peer-reviewed)abstract We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
45.	Cervin, Matti, et al. (author) The p Factor Consistently Predicts Long-Term Psychiatric and Functional Outcomes in Anxiety-Disordered Youth 2021 In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567. ; 60:7, s. 902-912 Journal article (peer-reviewed)abstract ObjectivePediatric anxiety disorders can have a chronic course and are considered gateway disorders to adult psychopathology, but no consistent predictors of long-term outcome have been identified. A single latent symptom dimension that reflects features shared by all mental health disorders, the p factor, is thought to reflect mechanisms that cut across mental disorders. Whether p predicts outcome in youth with psychiatric disorders has not been examined. We tested whether the p factor predicted long-term psychiatric and functional outcomes in a large naturalistically followed-up cohort of anxiety-disordered youth.MethodYouth enrolled in a randomized controlled treatment trial of pediatric anxiety during childhood/adolescence were followed-up on average six years posttreatment and then annually for four years. Structural equation modeling was used to estimate p at baseline. p and previously established predictors were modeled as predictors of long-term outcome.ResultsHigher levels of p at baseline were related to more mental health disorders, poorer functioning, and greater impairment across all measures at all follow-up time points. p predicted outcome above and beyond previously identified predictors, including diagnostic comorbidity at baseline. Post hoc analyses showed that p predicted long-term anxiety outcomes, but not acute treatment outcome, suggesting that p may be uniquely associated with long-term outcome.ConclusionYouth with anxiety disorders who present with a liability towards broad mental health problems may be at a higher risk for poor long-term outcome across mental health and functional domains. Efforts to assess and address this broad liability may enhance long-term outcome.
46.	Classen, Aimee T., et al. (author) Direct and indirect effects of climate change on soil microbial and soil microbial-plant interactions : What lies ahead? 2015 In: Ecosphere. - 2150-8925 .- 2150-8925. ; 6:8 Journal article (peer-reviewed)abstract Global change is altering species distributions and thus interactions among organisms. Organisms live in concert with thousands of other species, some beneficial, some pathogenic, some which have little to no effect in complex communities. Since natural communities are composed of organisms with very different life history traits and dispersal ability it is unlikely they will all respond to climatic change in a similar way. Disjuncts in plant-pollinator and plant-herbivore interactions under global change have been relatively well described, but plant-soil microorganism and soil microbe-microbe relationships have received less attention. Since soil microorganisms regulate nutrient transformations, provide plants with nutrients, allow co-existence among neighbors, and control plant populations, changes in soil microorganism-plant interactions could have significant ramifications for plant community composition and ecosystem function. In this paper we explore how climatic change affects soil microbes and soil microbe-plant interactions directly and indirectly, discuss what we see as emerging and exciting questions and areas for future research, and discuss what ramifications changes in these interactions may have on the composition and function of ecosystems.
47.	Crossfield, Ian J. M., et al. (author) 197 CANDIDATES AND 104 VALIDATED PLANETS IN K2's FIRST FIVE FIELDS 2016 In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 226:1 Journal article (peer-reviewed)abstract We present 197 planet candidates discovered using data from the first year of the NASA K2 mission (Campaigns 0-4), along with the results of an intensive program of photometric analyses, stellar spectroscopy, high-resolution imaging, and statistical validation. We distill these candidates into sets of 104 validated planets (57 in multi-planet systems), 30 false positives, and 63 remaining candidates. Our validated systems span a range of properties, with median values of R-P = 2.3 R-circle plus, P = 8.6 days, T-eff = 5300 K, and Kp = 12.7 mag. Stellar spectroscopy provides precise stellar and planetary parameters for most of these systems. We show that K2 has increased by 30% the number of small planets known to orbit moderately bright stars (1-4 R-circle plus, Kp = 9-13. mag). Of particular interest are 76 planets smaller than 2 R-circle plus, 15 orbiting stars brighter than Kp = 11.5. mag, 5 receiving Earth-like irradiation levels, and several multi-planet systems-including 4 planets orbiting the M dwarf K2-72 near mean-motion resonances. By quantifying the likelihood that each candidate is a planet we demonstrate that our candidate sample has an overall false positive rate of 15%-30%, with rates substantially lower for small candidates (<2 R-circle plus) and larger for candidates with radii >8 R-circle plus and/or with P < 3 days. Extrapolation of the current planetary yield suggests that K2 will discover between 500 and 1000 planets in its planned four-year mission, assuming sufficient follow-up resources are available. Efficient observing and analysis, together with an organized and coherent follow-up strategy, are essential for maximizing the efficacy of planet-validation efforts for K2, TESS, and future large-scale surveys.
48.	Daniel, Terry C., et al. (author) Contributions of cultural services to the ecosystem services agenda 2012 In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:23, s. 8812-8819 Journal article (peer-reviewed)abstract Cultural ecosystem services (ES) are consistently recognized but not yet adequately defined or integrated within the ES framework. A substantial body of models, methods, and data relevant to cultural services has been developed within the social and behavioral sciences before and outside of the ES approach. A selective review of work in landscape aesthetics, cultural heritage, outdoor recreation, and spiritual significance demonstrates opportunities for operationally defining cultural services in terms of socioecological models, consistent with the larger set of ES. Such models explicitly link ecological structures and functions with cultural values and benefits, facilitating communication between scientists and stakeholders and enabling economic, multicriterion, deliberative evaluation and other methods that can clarify tradeoffs and synergies involving cultural ES. Based on this approach, a common representation is offered that frames cultural services, along with all ES, by the relative contribution of relevant ecological structures and functions and by applicable social evaluation approaches. This perspective provides a foundation for merging ecological and social science epistemologies to define and integrate cultural services better within the broader ES framework.
49.	Davis, TH, et al. (author) Problem-based learning of research skills 2006 In: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 39:1, s. 120-128 Journal article (peer-reviewed)abstract Purpose: To determine whether a short-term, problem-based educational intervention leads to increased research activity among health care practitioners. Subjects and Methods: Participant's success was evaluated as a composite of 2 outcomes. These were (1) reporting results for the project designed during the practicum and (2) conducting subsequent research activities. The study population included 36 clinical research outcomes projects developed by clinical practitioners, postgraduate trainees, and medical students during 6 separate practicums. All project teams received the same educational intervention, an "outcomes research practicum" that was divided into 4 primary learning modules administered over a I to 4 month period. Each module included a preparatory videotape lecture, supplemental readings, and a 90-minute interactive laboratory session during which faculty members worked with participants to develop answers to a series of predefined questions relating to the design of clinical outcomes research projects. Follow-up continued for a minimum of 12 months and a maximum of 36 months. Results: Eighty-three percent of project teams completed all 4 practicum modules, and 69% completed one of the study outcomes (50% completed their research project and 47% completing a subsequent research activity). Practitioners were more likely to complete subsequent research activities, whereas trainees were more likely to complete their study project. Discussion: This short-term, problem-based educational intervention was successful in increasing the collective research activities of participants. Further, more rigorous structured research is needed to determine the ultimate impact on practice change and patient outcomes. (c) 2006 Elsevier Inc. All rights reserved.
50.	Ekhtiari, Hamed, et al. (author) A methodological checklist for fMRI drug cue reactivity studies : development and expert consensus 2022 In: Nature Protocols. - : Nature Portfolio. - 1754-2189 .- 1750-2799. ; 17:3, s. 567-595 Journal article (peer-reviewed)abstract Cue reactivity measured by functional magnetic resonance imaging is used in studies of substance-use disorders. This Consensus Statement is the result of a Delphi process to arrive at parameters that should be reported in describing these studies. Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: Participants Characteristics, General fMRI Information, General Task Information, Cue Information, Craving Assessment Inside Scanner, Craving Assessment Outside Scanner and Pre- and Post-Scanning Considerations. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the General fMRI Information category were reported in 90.5% of the reviewed papers, items in the Pre- and Post-Scanning Considerations category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.

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