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1.	Ademuyiwa, Adesoji O., et al. (author) Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries 2016 In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4 Journal article (peer-reviewed)abstract Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
2.	Hibar, Derrek P., et al. (author) Novel genetic loci associated with hippocampal volume 2017 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8 Journal article (peer-reviewed)abstract The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
3.	Hillier, Ladeana W, et al. (author) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution 2004 In: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716 Journal article (peer-reviewed)abstract We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
4.	Jacobs, Kevin B, et al. (author) Detectable clonal mosaicism and its relationship to aging and cancer. 2012 In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658 Journal article (peer-reviewed)abstract In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
5.	Haghighi, Mona, et al. (author) A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study 2016 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6 Journal article (peer-reviewed)abstract Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
6.	Faber, Zachary J, et al. (author) The genomic landscape of core-binding factor acute myeloid leukemias 2016 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556 Journal article (peer-reviewed)abstract Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
7.	Holmfeldt, Linda, et al. (author) The genomic landscape of hypodiploid acute lymphoblastic leukemia 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252 Journal article (peer-reviewed)abstract The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
8.	Shalaly, Nancy Dekki, et al. (author) Positive Modulation of the Glycine Receptor by Means of Glycine Receptor-Binding Aptamers 2015 In: Journal of Biomolecular Screening. - : Sage Publications. - 1087-0571 .- 1552-454X. ; 20:9, s. 1112-1123 Journal article (peer-reviewed)abstract According to the gate control theory of pain, the glycine receptors (GlyRs) are putative targets for development of therapeutic analgesics. A possible approach for novel analgesics is to develop a positive modulator of the glycine-activated Cl- channels. Unfortunately, there has been limited success in developing drug-like small molecules to study the impact of agonists or positive modulators on GlyRs. Eight RNA aptamers with low nanomolar affinity to GlyR1 were generated, and their pharmacological properties analyzed. Cytochemistry using fluorescein-labeled aptamers demonstrated GlyR1-dependent binding to the plasma membrane but also intracellular binding. Using a fluorescent membrane potential assay, we could identify five aptamers to be positive modulators. The positive modulation of one of the aptamers was confirmed by patch-clamp electrophysiology on L(tk) cells expressing GlyR1 and/or GlyR1. This aptamer potentiated whole-cell Cl- currents in the presence of low concentrations of glycine. To our knowledge, this is the first demonstration ever of RNA aptamers acting as positive modulators for an ion channel. We believe that these aptamers are unique and valuable tools for further studies of GlyR biology and possibly also as tools for assay development in identifying small-molecule agonists and positive modulators.
9.	Wang, Zhaoming, et al. (author) Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33 2014 In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633 Journal article (peer-reviewed)abstract Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
10.	Andersson, Anna, et al. (author) The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. 2015 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:4, s. 192-330 Journal article (peer-reviewed)abstract Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.
11.	Andersson, Kristin, et al. (author) Prospective Study of Human Papillomavirus Seropositivity and Risk of Nonmelanoma Skin Cancer 2012 In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 175:7, s. 685-695 Journal article (peer-reviewed)abstract Cutaneous human papillomaviruses (HPVs) have been associated with squamous cell carcinoma (SCC) in case-control studies, but there are limited data from prospective studies assessing whether virus exposure predicts risk of future cancer development. Two major biobanks, the Southern Sweden Microbiology Biobank (1971-2003) and the Janus Biobank (1973-2003) in Norway, containing samples from 850,000 donors, were searched for incident skin cancer for up to 30 years using registry linkages. Altogether, 2,623 donors with samples taken before diagnosis of SCC or basal cell carcinoma (BCC) of the skin were identified. Prediagnostic samples and samples from 2,623 matched controls were tested for antibodies against 33 types of HPV. Baseline seropositivity to HPV types in genus beta species 2 was associated with SCC risk (odds ratio = 1.3, 95% confidence interval: 1.1, 1.7); this was also the case for samples taken more than 18 years before diagnosis (odds ratio = 1.8, 95% confidence interval: 1.1, 2.8). Type-specific persistent seropositivity entailed elevated point estimates for SCC risk for 29 HPV types and decreased point estimates for only 3 types. After multiple hypothesis adjustment, HPV 76 was significantly associated with SCC risk and HPV 9 with BCC risk. In summary, seropositivity for certain HPV types was associated with an increased risk for future development of SCC and BCC.
12.	Andersson, Lars Gustaf, et al. (author) Inledning: David Aquilon, Magisk cirkel 2005 In: David Aquilon: Magisk cirkel. - 9197414220 ; , s. 1-8 Book chapter (other academic/artistic)abstract Introduction to the edition of the unfinished doctoral dissertation "Magisk cirkel" by David Aquilon (1965 - 1999), focusing on the films of Ingmar Bergman and expecially "The Serpent's Egg" (1977).
13.	Andersson, Staffan, 1959, et al. (author) Multiple receivers, multiple ornaments, and a trade-off between agonistic and epigamic signaling in a widowbird. 2002 In: The American naturalist. - : University of Chicago Press. - 1537-5323 .- 0003-0147. ; 160:5, s. 683-91 Journal article (peer-reviewed)abstract Sexual displays often involve several different ornamental traits. Yet most indicator models of sexual selection based on a single receiver (usually a choosy female) find that multiple handicap signals should be unstable. Here we study reasons for this contradiction, analyzing signal function, signal content, and trade-offs between signals in the polygynous red-collared widowbird Euplectes ardens. Males have both a long, graduated tail and a red carotenoid collar badge. Territory-holding "residents" have slightly shorter tails than the nonbreeding "floaters," but their carotenoid collars are 40% larger, and they have (on the basis of reflectance spectrometry and objective colorimetry) a 23-nm more long-wave ("redder") hue than floaters. This corroborates experimental evidence that the red collar is selected by male contest competition, whereas female choice is based almost exclusively on male tail length. Tail length is negatively correlated with the carotenoid signal, which together with body size and condition explains 55% of the variation in tail length. The trade-off in tail length and carotenoid investment is steeper among residents, suggesting an interaction with costs of territory defense. We propose that the "multiple receiver hypothesis" can explain the coexistence of multiple handicap signals. Furthermore, the trade-off between signal expressions might contribute to the inverse relation between nuptial tail elongation and coloration in the genus Euplectes (bishops and widowbirds).
14.	Andrikopoulos, Petros, et al. (author) Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide 2023 In: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1 Journal article (peer-reviewed)abstract The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
15.	Bombarda, F., et al. (author) Runaway electron beam control 2019 In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1 Journal article (peer-reviewed)
16.	Chew, Michelle S., et al. (author) Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index 2022 In: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 128:1, s. 26-36 Journal article (peer-reviewed)abstract BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality.METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE.RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds.CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE.CLINICAL TRIAL REGISTRATION: NCT03436238.
17.	Dahlin, Anna M., 1979-, et al. (author) A genome-wide association study on medulloblastoma 2020 In: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 147:2, s. 309-315 Journal article (peer-reviewed)abstract Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3).Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
18.	Di Saverio, Salomone, et al. (author) Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines 2020 In: World Journal of Emergency Surgery. - : BMC. - 1749-7922. ; 15:1 Research review (peer-reviewed)abstract Background and aims Acute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of non-operative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and peri-operative antibiotic therapy. Methods This executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA. Literature search has been updated up to 2019 and statements and recommendations have been developed according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by the participants to the consensus conference and by the board of co-authors, using a Delphi methodology for voting whenever there was controversy on a statement or a recommendation. Several tables highlighting the research topics and questions, search syntaxes, and the statements and the WSES evidence-based recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow chart for both adults and pediatric (< 16 years old) patients. Conclusions The 2020 WSES guidelines on AA aim to provide updated evidence-based statements and recommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicated AA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6) ,management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy.
19.	Di Saverio, Salomone, et al. (author) WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis 2016 In: World Journal of Emergency Surgery. - : BIOMED CENTRAL LTD. - 1749-7922. ; 11:34 Research review (peer-reviewed)abstract Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics.
20.	Farrell, Edward D. D., et al. (author) A baseline for the genetic stock identification of Atlantic herring, Clupea harengus, in ICES Divisions 6.a, 7.b-c 2022 In: Royal Society Open Science. - : The Royal Society. - 2054-5703. ; 9:9 Journal article (peer-reviewed)abstract Atlantic herring in International Council for Exploration of the Sea (ICES) Divisions 6.a, 7.b-c comprises at least three populations, distinguished by temporal and spatial differences in spawning, which have until recently been managed as two stocks defined by geographical delineators. Outside of spawning the populations form mixed aggregations, which are the subject of acoustic surveys. The inability to distinguish the populations has prevented the development of separate survey indices and separate stock assessments. A panel of 45 single-nucleotide polymorphisms, derived from whole-genome sequencing, were used to genotype 3480 baseline spawning samples (2014-2021). A temporally stable baseline comprising 2316 herring from populations known to inhabit Division 6.a was used to develop a genetic assignment method, with a self-assignment accuracy greater than 90%. The long-term temporal stability of the assignment model was validated by assigning archive (2003-2004) baseline samples (270 individuals) with a high level of accuracy. Assignment of non-baseline samples (1514 individuals) from Divisions 6.a, 7.b-c indicated previously unrecognized levels of mixing of populations outside of the spawning season. The genetic markers and assignment models presented constitute a 'toolbox' that can be used for the assignment of herring caught in mixed survey and commercial catches in Division 6.a into their population of origin with a high level of accuracy.
21.	Fazey, Ioan, et al. (author) Transforming knowledge systems for life on Earth : Visions of future systems and how to get there 2020 In: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70 Journal article (peer-reviewed)abstract Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
22.	Forslund, Sofia K., et al. (author) Combinatorial, additive and dose-dependent drug–microbiome associations 2021 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505 Journal article (peer-reviewed)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.
23.	Haggblade, Steven, et al. (author) Cassava Commercialization in Southeastern Africa 2012 In: Journal of Agribusiness in Developing and Emerging Economies. - : Emerald. - 2044-0839 .- 2044-0847. ; 2:1, s. 4-40 Journal article (peer-reviewed)abstract Purpose – Cassava production surged noticeably in Southeastern Africa beginning in the 1990s. The purpose of this paper is to examine the commercial responses and food security consequences of cassava production growth in the region. Design/methodology/approach – The paper incorporates a mix of quantitative analysis, based primarily on original analysis of national farm household survey data, together with key informant interviews with value chain participants in the three neighboring countries of Malawi, Mozambique and Zambia. Findings – In the cassava production zones, cassava's high productivity translates into per kilogram carbohydrate costs 60 per cent to 70 per cent of the cost of cereals such as maize and wheat, thereby opening up a range of profitable opportunities for commercialization of cassava-based foods, feeds and industrial products. Despite this potential, cassava commercialization in Southeastern Africa remains in its formative stages, with only 10 per cent to 30 per cent of production currently marketed. Unlike West Africa, where cassava commercialization has centered on marketing prepared cassava-based convenience foods, the emerging cassava markets in Southeastern Africa have centered on fresh cassava, low value-added cassava flour, and experiments in industrial processing of cassava-based starches, biofuels and feeds. Strategic investment in a set of key public goods (breeding, training in food sciences and food safety, and research on in-ground cassava storage) can help to shape this transition in ways that benefit both commercial interests and the food security of vulnerable households. Originality/value – The paper compares cassava commercialization across differing agro-climatic zones, policy environments and food staple zones.
24.	Hambäck, Peter A., et al. (author) Insekter och spindlar i anlagda våtmarker : Intressanta fynd från en systematisk undersökning i Uppland och södra Halland 2022 In: Entomologisk tidskrift. - 0013-886X. ; 143:1-2, s. 47-66 Journal article (peer-reviewed)abstract Wetland area has decreased dramatically compared with preindustrial times, and in manyagricultural areas almost all wetlands have been drained to gain cropland. The trend hasin recent years been reversed because society has realized the many benefits of wetlandfunctions, such as for nutrient retention and flood control. In this study we inventoried 75 wetlands in Uppland and Halland for insects and spiders with Malaise traps, pitfall traps andsuction sampling. Most included wetlands are constructed, because the main purpose was toexamine if these wetlands also can be good for arthropod diversity, but we also included somemore natural wetlands as comparison. In total, we identified more than 25,000 individualsof more than 900 species of Coleoptera, Araneae, Diptera and Heteroptera. We found onenew species for Sweden, Hilara manicata Meigen 1822, and 37 new regional records. Alarge number of species found are considered threatened or else rare. Some wetlands closeto Mälaren were particularly interesting, with three species (Hypsosinga heri (Hahn 1831),Rhaphium antennatum (Charlier 1835) and Bagous robustus Brisout de Barneville 1863)that have no records nearby during recent times. These and other species found in the studyshow that constructed wetlands can provide good habitats for arthropod biodiversity andrare species, particularly if wetland shores are grazed and trampled by cattle.
25.	Karlsson, Elinor K., et al. (author) Efficient mapping of mendelian traits in dogs through genome-wide association 2007 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:11, s. 1321-1328 Journal article (peer-reviewed)abstract With several hundred genetic diseases and an advantageous genome structure, dogs are ideal for mapping genes that cause disease. Here we report the development of a genotyping array with \|[sim]\|27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only \|[sim]\|20 dogs. Specifically, we map two traits with mendelian inheritance: the major white spotting (S) locus and the hair ridge in Rhodesian ridgebacks. For both traits, we map the loci to discrete regions of <1 Mb. Fine-mapping of the S locus in two breeds refines the localization to a region of \|[sim]\|100 kb contained within the pigmentation-related gene MITF. Complete sequencing of the white and solid haplotypes identifies candidate regulatory mutations in the melanocyte-specific promoter of MITF. Our results show that genome-wide association mapping within dog breeds, followed by fine-mapping across multiple breeds, will be highly efficient and generally applicable to trait mapping, providing insights into canine and human health.

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