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We aimed to identify cardiac function in patients with established mixed connective tissue disease (MCTD). This was a cross-sectional case–control study of well-characterised MCTD patients who had previously been included in a nationwide cohort. Assessments comprised protocol transthoracic echocardiography, electrocardiogram and blood samples. In patients only, we evaluated the findings of high-resolution pulmonary computed tomography and disease activity. We assessed 77 MCTD patients (mean age 50.5 ± 12.3 years) with a mean disease duration of 16.4 years, and 59 age- and sex-matched healthy controls (49.9 ± 11.7 years). By echocardiography, measures of left ventricular function, i.e. fractional shortening (38.1 ± 6.4% vs. 42.3 ± 6.6%, p

The Middle Neolithic sites on Gotland are characterized by variety in the handling of human remains. In addition to burials with complete and intact skeletons and package-burials, some contexts contain mutilated bodies, or they contain a few human bones or none. These practices have previously been interpreted as resulting from modern disturbances such as ploughing or pre-depositional treatment of dead bodies. Based on re-examination of the field documentation and C14-dates, I argue that the diverse ways of treating human skeletal remains represent post-depositional practices, and I propose that part of the mortuary practices was to reopen graves and exhume bones. During the Middle Neolithic, death might have been conceptualized as a process, and treatment of the dead and the buried could have been governed by a variety of emotions like grief, fear and reverence.

The genome of the soil Bacteroidota Chitinophaga pinensis encodes a large number of glycoside hydrolases with noteworthy features and potentially novel functions. Several are predicted to be active on polysaccharide components of fungal and oomycete cell walls, such as chitin, β-1,3-glucan, and β-1,6-glucan. While several fungal β-1,6-glucanase enzymes are known, relatively few bacterial examples have been characterised to date. We have previously demonstrated that C. pinensis shows strong growth using β-1,6-glucan as the sole carbon source, with efficient release of oligosaccharides from the polymer. We here characterise the capacity of the C. pinensis secretome to hydrolyse the β-1,6-glucan pustulan, and describe three distinct enzymes encoded by its genome, all of which show different levels of β-1,6-glucanase activity and which are classified in different glycoside hydrolase families. Our data show that C. pinensis has multiple tools to deconstruct pustulan, allowing the species broad utility of this substrate, with potential implications for bacterial biocontrol of pathogens via cell wall disruption. Oligosaccharides derived from fungal β-1,6-glucans are valuable in biomedical research and drug synthesis, and these enzymes could be useful tools for releasing such molecules from microbial biomass, an under-exploited source of complex carbohydrates.

Background/Aims Anti-synthetase syndrome (ASS) represents a distinct entity within myositis spectrum disorders; however, correct classification of patients with anti-tRNA synthetase autoantibodies and skin manifestations akin to dermatomyositis (DM) remains uncertain. Our aim was to compare clinical characteristics, skin involvement, and malignancy, between patients with ASS and DM, classified by disease-specific autoantibodies. Methods Data from 05/2009-03/2016 from 9 countries from the prospective, myositis EuroMyositis registry were downloaded. Those with anti-tRNA synthetase autoantibodies (Jo-1/PL-7/PL-12/OJ/EJ/KS) were classified as ASS, and those with Mi-2/TIF1-γ/NXP2/SAE/MDA5 autoantibodies as DM. Clinical phenotypes including malignancies (except skin malignancies) were tabulated. Characteristics of patients with skin involvement (excluding mechanic’s hands and Raynaud’s phenomenon) were compared using Fisher’s exact test with Bonferroni corrected p-values. Results Of 3,067 patients, 2,028 had autoantibody profiling results (66.1%), of which 783 (38.6%) were positive for at least one of the autoantibodies being considered. Five patients with dual autoantibody specificities were excluded. Of the remaining 778, 320 (41.1%) were classified as DM, and 458 (58.9%) as ASS. Median age at diagnosis was 48.2 years (interquartile range [IQR] 37.5 to 57.8) in the DM cohort and 49 (IQR 38.3 to 62.2) in the ASS cohort. Skin involvement was present in 277 (86.6%) DM patients (DM skin) vs 204 (44.5%) ASS patients (ASS skin) (pcorr Conclusion Patients with ASS have frequent skin involvement but also a distinct clinical phenotype compared to DM. These findings may inform the development of future classification criteria for ASS. Disclosure R.M. Hum: None. J.B. Lilleker: None. J.A. Lamb: None. W.E. Ollier: None. G. Wang: None. L.R. Wedderburn: None. L.P. Diederichsen: None. J. Schmidt: None. P. Oakley: None. O. Benveniste: None. M.G. Danieli: None. K. Danko: None. N.T.P. Thuy: None. M.V.D. Mercado: None. H. Andersson: None. B.D. Paepe: None. J.L.D. Bleecker: None. B. Maurer: None. L.J. McCann: None. N. Pipitone: None. N. McHugh: None. P. New: None. J. Vencovsky: None. I.E. Lundberg: None. H. Chinoy: None.

VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome) first described in 2020, is caused by a limited repertoire of somatic mutations in UBA1, a gene involved in the initiation of ubiquitination. Ubiquitination, adding an ubiquitin protein to a substrate protein, can have various effects on the substrate. Disruption of UBA1 function results in diverse clinical manifestations, mimicking a variety of disorders.A man in his sixties presented with fever, chest pain, fatigue, pulmonary infiltrates and elevated acute phase reactants. Initially he was thought to have extra-cranial giant cell arteritis. When he developed ear and nose chondritis, a revised diagnosis of relapsing polychondritis was made. Subsequently he developed macrocytic anaemia and thrombocytopenia. His condition remained resistant to medical therapy and he died eight years after disease onset. Analysis of stored DNA revealed a somatic mutation in UBA1 confirming the diagnosis of VEXAS syndrome.VEXAS syndrome is a newly identified inflammatory disorder due to an acquired mutation in haematopoietic bone marrow cells in older men. The syndrome may be misdiagnosed as treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome or giant cell arteritis. We describe the first individual with molecularly confirmed VEXAS syndrome in Norway.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of complex autoimmune conditions characterized by inflammation in skeletal muscle and extramuscular compartments, and interferon (IFN) system activation. We undertook this study to examine the contribution of genetic variation to disease susceptibility and to identify novel avenues for research in IIMs.METHODS: Targeted DNA sequencing was used to mine coding and potentially regulatory single nucleotide variants from ~1,900 immune-related genes in a Scandinavian case-control cohort of 454 IIM patients and 1,024 healthy controls. Gene-based aggregate testing, together with rare variant- and gene-level enrichment analyses, was implemented to explore genotype-phenotype relations.RESULTS: Gene-based aggregate tests of all variants, including rare variants, identified IFI35 as a potential genetic risk locus for IIMs, suggesting a genetic signature of type I IFN pathway activation. Functional annotation of the IFI35 locus highlighted a regulatory network linked to the skeletal muscle-specific gene PTGES3L, as a potential candidate for IIM pathogenesis. Aggregate genetic associations with AGER and PSMB8 in the major histocompatibility complex locus were detected in the antisynthetase syndrome subgroup, which also showed a less marked genetic signature of the type I IFN pathway. Enrichment analyses indicated a burden of synonymous and noncoding rare variants in IIM patients, suggesting increased disease predisposition associated with these classes of rare variants.CONCLUSION: Our study suggests the contribution of rare genetic variation to disease susceptibility in IIM and specific patient subgroups, and pinpoints genetic associations consistent with previous findings by gene expression profiling. These features highlight genetic profiles that are potentially relevant to disease pathogenesis.

Cervical screening is increasingly switching to human papillomavirus (HPV) testing. In many settings, the switch has involved one or several co-tests (testing using both cytology and HPV) in the screening guidelines, to ensure safety. When Sweden switched to HPV testing in 2015 the guidelines included a co-test at age 41. To evaluate the effect of co-testing, we identified all 208,701 women resident in Sweden who in 2019 were 40-42 years old and thus eligible for co-testing. All cervical samples, the results of the test and of the subsequent biopsies were identified in the Swedish National Cervical Screening Registry. Out of the 10,643 women with co-testing in screening, there were 197 women with a subsequent biopsy with high-grade cervical neoplasia or worse (CIN2+). Among these 197 women, 189 had a screening test positive for both HPV and cytology, 6 women were HPV+/Cyt- and 2 women were HPV-/Cyt+. There were 7115 women with a co-test outside of the screening program. Among these, 325 women had a CIN2+ in histopathology, 290 were double positive, 13 women were cyt+/HPV-, and 11 women each were HPV+/cyt- and HPV-/Cyt-. In summary, the additional yield of CIN2+ with co-testing was 2 cases per 10,643 women as compared with 195/10,643 CIN2+ cases detected with HPV screening alone. However, for cervical samples taken outside the screening program (e.g. taken on a clinical indication) there was an increased yield (314 CIN2+ cases detected with co-testing as compared to 301 cases with HPV screening).

Syftet med föreliggande kvalitativa studie är att undersöka hur pedagoger i förskolan beskriver att de arbetar med matematik genom digitala verktyg. Utifrån de nya kraven i Läroplan för förskolan Lpfö 18 (2018) om att pedagoger ska bedriva undervisning i förskolans verksamhet och de nytillkomna begrepp som relaterar till digitalisering ansåg vi att detta område var intressant att studera inför vårt kommande arbete i förskolan. Pedagoger uttrycker att de har otillräcklig digital kompetens och inte är intresserade av att arbeta med digitala verktyg i förskolan, vilket därmed kan bli problematiskt (Forsling 2011). Den brist på tidigare forskning inom området gjorde oss dessutom mer nyfikna och intresserade eftersom vi idag lever i ett digitaliserat samhälle där olika tekniker finns i vardagen. Metoden som användes för att samla in materialet till studien var en enkätundersökning i form av webbenkät, vilken delades på ett internetforum och mejlades till yrkessamma pedagoger i förskolan. Underlaget för studien blev svar från 18 pedagoger. Det insamlade materialet analyserades med hjälp av ett sociokulturellt perspektiv, begreppen artefakter och mediering samt TPACK-modellen. Slutresultatet visar att matematik anses vara ett naturligt inslag i förskolan där pedagoger använder teknik som både är analog och digital i sin matematikundervisning för att stödja barns förståelse för ämnet och samtidigt erbjuda barn möjlighet att erövra digital kompetens. Digitala verktyg anses utifrån dess breda utbud, innehåll och funktioner skapa möjligheter men även begränsningar i relation till pedagogers undervisning och barns lärprocess i matematik. Slutresultatet visar även att pedagogers kompetenser, intresse och förhållningssätt till matematik och digitala verktyg är betydande för hur digital teknik används i verksamheten. Det framkom dessutom att det kan uppstå didaktiska utmaningar kring användningen av digitala verktyg i relation till dess variationsrikedom och problematik utifrån bristen av forskning för pedagoger att förhålla sig till i deras arbete med digital teknik när de blir ifrågasatta av vårdnadshavare.

Deep brain stimulation (DBS) is a an established therapy in neurological and mental disorders making use of electrical pulses chronically delivered to a certain disease-specific neural target through surgically implanted electrodes. The therapeutical effect of DBS is highly individual and depends on the target coverage by the stimuli and the amount of spill beyond it. This can be suitably formulated as an optimization problem. Since the biological mechanism underlying the DBS therapy is mainly unknown, and due to high inter-patient and intra-patient variability of the DBS effect, a pragmatic approach to the DBS programming is to consider the process as tuning of a control system for the symptoms. Such a technology assumes that the symptoms are accurately quantified. The paper summarizes the progress in the individualized DBS and presents the results of a limited clinical study making use of the proposed DBS programming approach.

Background:Based on the argument that symptoms define disease, physicians commonly apply the terms “preclinical” or “subclinical” disease to describe patients with disease-related findings but no accompanying symptoms for connective tissue disease associated interstitial lung disease (CTD-ILD). The term subclinical frequently applies to patients with mild ILD changes on high resolution chest tomography (HRCT), normal forced vital capacity (FVC), and without respiratory symptoms. Previous work in systemic sclerosis (SSc)-ILD did show that patients with even minor extent of ILD at baseline often progressed and had increased mortality risk, suggesting that it is not appropriate to define these patients as “subclinical.”Objectives:To identify the prevalence of subclinical ILD across CTD diagnoses, and assess the rate of progression of lung fibrosis compared to CTD without ILD and with clinical ILD.Methods:All CTD patients, including SSc, anti-synthetase syndrome (ASS) and mixed connective tissue disease (MCTD) from the Oslo University Hospital diagnosed before 2015 and assessed for the presence of ILD by HRCT were included. The year 2015 was chosen to secure an observation time of at least five years from ILD diagnosis to study end on 01.01.2021 or time of death. All patients fulfilled the respective CTD classification criteria. Subclinical ILD was defined as an ILD extent 80% predicted and without respiratory symptoms. Clinical ILD was defined as >5% extent of ILD or Results:We identified 525 CTD patients, including 296 with SSc, 135 with MCTD and 94 with ASS who had conducted a baseline HRCT. Of these, 227 (43%) had no ILD, 67 (13%) subclinical and 231 (44%) clinical ILD (Table). Of the 67 subclinical ILD patients, 45 (15%) had SSc, 13 (10%) MCTD and 9 (10%) ASS of thespecific cohorts. Over a median time of 4.5 years between baseline and follow-up HRCT, 95/395 (24%) showed progression of ILD, including 72 (26%) SSc and 23 (19%) MCTD patients. Disease progression frequently occurred in both subclinical ILD (38%) and clinical ILD (51%) patients (Figure). Age, gender, underlying CTD, and baseline lung function were not predictive for the progression of lung fibrosis. Progression was too infrequent to allow for meaningful multivariable regression analyses. After a median observation period of 12 years, 153 (29%) of the patients died. The 1-, 5- and 10-year survival rates in those without ILD, subclinical and clinical ILD were 97%/97%/99%, 88%/91%/82%, and 82%/85%/68% (pTable 1.Clinical characteristics, demographics and outcomeNo ILD (n=227)Subclinical ILD (n=67)Clinical ILD (n=231)Age, y (SD)50 (15.4)51 (14.4)52 (15.3)Male sex, n (%)89 (39)22 (33)111 (48)Deceased, n (%)50 (22)12 (18)91 (39)Observation period, y median (range)13.7 (18.6)13.9 (17.9)11.5 (17.1)FVC% (SD)97 (18.6)99 (17.9)81 (20.9)FVC decline% (SD)-0.70 (11.1)-0.81 (16.5)-1.61 (15.9)DLCO% (SD)73 (19.4)73 (16.9)55 (17.4)Extent of ILD% (SD)0 (0)2.3 (1.5)19.3 (16.8)ILD progression% (SD)0.08 (1.0)3.1 (6.2)3.6 (9.9)ILD progressors, n (%)3 (2)20 (38)72 (51)Figure 1.Time to ILD progression in CTD without ILD, with subclinical and clinical ILDConclusion:Subclinical ILD is frequently present across CTDs and progresses over time in a substantial subgroup of patients, comparable to patients with clinical ILD. Our findings question the terms sub- and preclinical ILD, which may potentially lead to a suboptimal “watchful waiting management strategy”. Monitoring all CTD patients with any ILD is of high importance to identify disease progression early.Disclosure of Interests:Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Lilly and Medscape, Consultant of: Actelion, Boehringer Ingelheim, Bayer, ARXX, and Medscape, Grant/research support from: Boehringer Ingelheim, Helena Andersson: None declared, Silje Reiseter: None declared, Håvard Fretheim Consultant of: Actelion, Bayer., Imon Barua: None declared, Torhild Garen: None declared, Øyvind Midtvedt: None declared, Ragnar Gunnarsson: None declared, Mike Durheim Speakers bureau: Boehringer Ingelheim and Roche, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim, Trond M Aaløkken: None declared, Øyvind Molberg: None declared

Leaching of phosphorus (P) from agricultural land is a major contributor to eutrophication of surface waters in many countries, and effective mitigation options to reduce P in leachate are needed. In this study, intact columns (0.77 m deep) of subsoil from three Swedish agricultural soils (one sand and two clay) were used to examine whether placing quicklime (calcium oxide, CaO) on the subsoil could reduce P leaching over a 3-yr period. Leaching of particulate P (PP) was significantly less from clay soil columns with lime than from clay soil columns without (P

Objective.Interstitial lung disease (ILD) is a major component of the antisynthetase syndrome, but quantitative data on longterm pulmonary outcome in antisynthetase syndrome are limited. In this study, the main aims were to compare pulmonary function tests (PFT) and the 6-min walking distance (6MWD) between patients with antisynthetase syndrome and healthy sex- and age-matched controls, to evaluate the extent of ILD by lung high-resolution computed tomography (HRCT), and to assess correlations between PFT measures and ILD extent.Methods.Concurrent PFT and 6MWD were performed in 68 patients with antisynthetase syndrome and their individually matched controls. Additionally, in the patients, the extent of ILD was determined in 10 HRCT sections, expressed as percentage of total lung volumes.Results.Median disease duration in the antisynthetase syndrome cohort was 71 months. Compared with the matched controls, the patients with antisynthetase syndrome had mean 28%, 27%, and 53% lower absolute values of forced vital capacity (FVC), forced expiratory volume in 1 s, and DLCO (p < 0.001). Mean difference in 6MWD between patients and controls was 116 m (p < 0.001). Median extent of ILD by HRCT was 20% (range 0–73) and correlated with FVC and DLCO. Pulmonary outcome did not differ between Jo1 and non-Jo1 subsets.Conclusion.To our knowledge, this study is the first to demonstrate a highly significant difference in PFT between patients with antisynthetase syndrome with 6 years of followup and healthy controls. DLCO displayed the highest difference with mean 53% lower value in the patients. FVC and DLCO correlated significantly with ILD extent, indicating these variables as appropriate outcome measures in antisynthetase syndrome–associated ILD.

Background Mortality as an outcome of disease’s severity and causes of death can give extended insight into the nature of each specific diagnose and highlight distinct needs for monitoring. In connective tissue diseases (CTD) and systemic vasculitides, mortality and causes of death have been studied within most single diseases, but with heterogeneity of the studies and widely varying results. Studies applying similar methods across the diagnoses are lacking. Consequently, it is difficult to compare causes of death between the different diagnoses. 1 Objectives To identify the causes of death within different CTDs and systemic vasculitides. Methods We performed a prospective, observational, controlled study between 1999 and 2017 of adult patients (at least 18 years of age) with diagnosis of CTD or vasculitides. All patients were included in the Norwegian connective tissue disease and vasculitis Registry (NOSVAR). In total, 2140 patients were diagnosed and followed up until death or study end by April 31th 2017. To avoid bias by selection, we included only incident cases, excluding patients with diagnoses set prior to 1999. Moreover, cases with a disease course not consistent with the initial diagnoses were excluded. Causes of death were identified by linking NOSVAR to the Norwegian Causes of Death Registry and by reviewing hospital charts. We divided the causes of death into the main groups of cardiovascular diseases (CVD), neoplasms, chronic respiratory disease (CRD), infections and other (gastrointestinal, renal insufficiency and trauma. To compare causes of death to the general population we used data from WHO Mortality Database, Causes of death. 2 Results During a mean (SD) follow-up time of 9.2 years (4.7), 279 patients (13%) deceased. The major causes of death were, in descending order of frequency; CVD (27%), neoplasms (25%), CRD (16%), infections (11%), gastrointestinal manifestations (4%), renal insufficiency (2%). Data from the general population, adjusted for age and gender, showed that deaths by CVD, CRD and infections were more prevalent among the patients. 2 The leading causes of death are shown in figure 1. In Takayasu arteritis and lSSc, CVD was the most frequent cause of death; (56%) and (41%), respectively. More than half of the patients (53%) with antisynthetase syndrome died of CRD. Those with dematomyositis died most frequently of neoplasms (50%). Conclusions Compared to general population, patients with CTD and vasculitidis died more often of CVD, CRD and infections. CVD as a cause of death was most prevalent in patients with Takayasu arteritis, giant cell arteritis and systemic sclerosis, while neoplasm was the major cause of death in dermatomyositis. In antisynthetase syndrome, both CRD was the major causes of death. The study gives the clinician valuable information on how to monitoring the different CTDs and vasculitidis regarding serious outcome. References [1] Toledano E, Candelas G, Rosales Z, Martinez Prada C, Leon L, Abasolo L, et al. A meta-analysis of mortality in rheumatic diseases. Reumatologia clinical2012;8(6):334–41. [2] University of Washington, Causes of Death (COD) visualization VizHub. https:/vizhub.healthdata.org/cod/University of Washington;2017 [updated 2017cited2017]. Disclosure of Interest None declared

To retrospectively evaluate the efficacy and safety of rituximab (Rtx) treatment in patients with anti-synthetase syndrome (ASS) and severe interstitial lung disease (ILD).Patients with severe ILD and12 months follow-up post-Rtx were identified from the Oslo University Hospital ASS cohort (n = 112). Clinical data, including pulmonary function tests (PFTs), were retrospectively collected from medical reports. Extent of ILD pre-, and post-Rtx was scored on thin-section high-resolution CT (HRCT) images and expressed as a percentage of total lung volume. Muscle strength was evaluated by manual muscle testing of eight muscle groups (MMT8).Altogether, 34/112 ASS patients had received Rtx; 24/34 had severe ILD and12 months follow-up post-Rtx (median 52 months). In these 24 patients, the median percentage of predicted forced vital capacity, forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lungs for carbon monoxide (DLCO) increased by 24%, 22% and 17%, respectively, post-Rtx. Seven patients (all with disease duration12 months and/or acute onset/exacerbation of ILD) had30% improvement in all three PFTs. HRCT analysis showed a median 34% reduction in ILD extent post-Rtx. MMT8 score increased post-Rtx. During follow-up, 7/34 (21%) Rtx-treated ASS patients died; 6/7 deaths were related to infections. The mortality rate in the Rtx-treated group was comparable to that of the remaining ASS cohort (25/78 deceased; 32%).This study, which included 24 Rtx-treated ASS patients with severe ILD, reports improved PFTs after a median 52 months follow-up post-Rtx. The best outcome was observed in patients with a disease duration12 months and/or acute onset/exacerbation of ILD. The study indicates that Rtx could be a treatment option for selected ASS patients, but infections should be given attention.

The importance of subsoil features for phosphorus (P) leaching is frequently mentioned, but subsoil effects are still poorly documented. This study examined whether the subsoil of four agricultural Swedish soils (two sand and two clay) functioned as a source or sink for P leaching by measuring P leaching from intact soil columns with topsoil (1.05 m deep) and without topsoil (0.77 m deep) over 3 yr. One sandy soil with high topsoil P content (Olsen P, 84 mg kg) and high subsoil sorption capacity (P sorption index [PSI], 3.7 mmol kg) had low leaching of dissolved reactive P (DRP) from full-length and subsoil lysimeters (0.12 and 0.08 kg ha yr, respectively). The other sandy soil, with high Olsen P content in the topsoil and subsoil (27 and 19 mg kg, respectively) and low PSI in the subsoil (1.4 mmol kg), had high DRP leaching from full-length and subsoil lysimeters (3.33 and 3.29 kg ha yr, respectively). High P content at depth (Olsen P, 21 mg kg) in one clay soil resulted in relatively higher subsoil DRP contribution (89%) to total leaching than observed in the other clay soil (71%). These results indicate that the subsoil can act as source or sink for P leaching, depending on P content, degree of P saturation, and P sorption capacity, and therefore subsoil properties should be considered when selecting mitigation measures to reduce P leaching.

Transport of phosphorus (P) from agricultural fields to water bodies deteriorates water quality and causes eutrophication. To reduce P losses and optimize P use efficiency by crops, better knowledge is needed of P turnover in soil and the efficiency of best management practices (BMPs). In this review, we examined these issues using results from 10 Swedish long-term soil fertility trials and various studies on subsurface losses of P. The fertility trials are more than 50 years old and consist of two cropping systems with farmyard manure and mineral fertilizer. One major finding was that replacement of P removed by crops with fertilizer P was not sufficient to maintain soil P concentrations, determined with acid ammonium lactate extraction. The BMPs for reducing P leaching losses reviewed here included catch crops, constructed wetlands, structure liming of clay soils, and various manure application strategies. None of the eight catch crops tested reduced P leaching significantly, whereas total P loads were reduced by 36% by wetland installation, by 39 to 55% by structure liming (tested at two sites), and by 50% by incorporation of pig slurry into a clay soil instead of surface application. Trend analysis of P monitoring data since the 1980s for a number of small Swedish catchments in which various BMPs have been implemented showed no clear pattern, and both upward and downward trends were observed. However, other factors, such as weather conditions and soil type, have profound effects on P losses, which can mask the effects of BMPs.

The promotion of students’ engagement with school is an internationally acknowledged challenge in education. There is a need to examine the structure of the concept of student engagement and to discover the best practices for fostering it across societies. That is why the cross-cultural invariance testing of students’ engagement measures is highly needed. This study aimed, first, to find the reduced set of theoretically valid items to represent students’ affective and cognitive engagement forming the Brief-SEI (brief version of the Student Engagement Instrument; SEI). The second aim was to test the measurement invariance of the Brief-SEI across three countries (Denmark, Finland, and Portugal). A total of 4,437 seventh-grade students completed the SEI questionnaires in the three countries. The analyses revealed that of the total 33 original instrument items, 15 items indicated acceptable psychometric properties of the Brief-SEI. With these 15 items, cross-national factorial validity and invariances across genders and students with different levels of academic performance (samples from Finland and Portugal) were demonstrated. This article discusses the utility of the Brief-SEI in cross-cultural research and its applicability in different national school contexts.

Deep Brain Stimulation (DBS) is a well-established treatment in neurodegenerative diseases, e.g. Parkinson's Disease. It consists of delivering electrical stimuli to a target in the brain via a chronically implanted lead. To expedite the tuning of DBS stimuli to best therapeutical effect, mathematical models have been developed during recent years. The electric field produced by the stimuli in the brain for a given lead position is evaluated by numerically solving a Partial Differential Equation with the medium conductivity as a parameter. The latter is patient- and target-specific but difficult to measure in vivo. Estimating brain tissue conductivity through medical imaging is feasible but time consuming due to registration, segmentation and post-processing. On the other hand, brain atlases are readily available and processed. This study analyzes how alternations in the conductivity due to inter-patient variability or lead position uncertainties affect both the stimulation shape and the activation of a given target. Results suggest that stimulation shapes are similar, with a Dice's Coefficient between 93.2 and 98.8%, with a higher similarity at lower depths. On the other hand, activation shows a significant variation of 17 percentage points, with most of it being at deeper positions as well. It is concluded that, as long as the lead is not too deep, atlases can be used for conductivity maps with acceptable accuracy instead of fully individualized though medical imaging models.

Deep Brain Stimulation (DBS) is an established therapy for treating e.g. Parkinson's disease, essential tremor, as well as epilepsy. In DBS, chronic pulsatile electrical stimulation is administered to a certain target area of the brain through a surgically implanted lead. The stimuli parameters have to be properly tuned in order to achieve therapeutical effect that in most cases is alleviation of motor symptoms. Tuning of DBS currently is a tedious task since it is performed manually by medical personnel in a trial-and-error manner. It can be dramatically improved and expedited by means of recently developed mathematical models together with control and estimation technology. This paper presents a control engineering perspective on DBS, viewing it as a control system for minimizing the severity of the symptoms through coordinated manipulation of the stimuli parameters. The DBS model structure comprises a stimuli model, an activation model, and a symptoms model. Each of those is individualized from patient data obtained through medical imaging, electrical measurements, and objective symptom quantification. The proposed approach is illustrated by simulation and clinical data from an individualized DBS model being developed by the authors.

Eutrophication, a major problem in many fresh and brackish waters, is largely caused by nonpoint-source pollution by P from agricultural soils. This lysimeter study examined the influence of P content, physical properties, and sorption characteristics in topsoil and subsoil on P leaching measured during 21 mo in 1-m-long, undisturbed soil columns of two clay and two sandy soils. Total P losses during the period varied between 0.65 and 7.40 kg ha. Dissolved reactive P was the dominant form in leachate from the sandy soils and one clay soil, varying from 48 to 76%. Particulate P dominated in leachate from the other clay soil, where low pH (5.2) in the subsoil decreased aggregate stability and thereby probably increased the dispersion of clay particles. Phosphorus leaching was small from soils with high P sorption index (PSI) and low P saturation (10% of PSI) in the subsoil, even though extractable P (Olsen P) in the topsoil was high, and large from a soil with low sorption capacity and high P saturation (35% of PSI) in the profile. High sorption capacity in the subsoil was more important for P leaching in sandy soils than in clay soils with macropore flow, where the effect of high sorption capacity was reduced due to less interaction between percolating water and the soil matrix. The results suggest that P leaching is greatly affected by subsoil properties and that topsoil studies, which dominate current research, are insufficient for assessing P leaching in many soils.

We thank Cavagna et al 1 for their thoughtful analysis relating to our recent publication.2 Several important points are raised, many of which we also referred to. It is of great interest and reassurance that the demographics and clinical features of antisynthetase syndrome (ASS) are broadly similar between the AENEAS (American and European NEtwork of Anti-Synthetase syndrome) and EuroMyositis cohorts. Clearly the frequency of interstitial lung disease and arthritis differs due to the sources of case ascertainment. This highlights …

A huge number of different analyses are performed in modern clinical chemistry laboratories. Therefore the highest possible degree of automation is necessary to decrease the turnaround time (TAT) a...

Objective Deep brain stimulation (DBS) consists of delivering electrical stimuli to a brain target via an implanted lead to treat neurological and psychiatric conditions. Individualized stimulation is vital to ensure therapeutic results, since DBS may otherwise become ineffective or cause undesirable side effects. Since the DBS pulse generator is battery-driven, power consumption incurred by the stimulation is important. In this study, target coverage and power consumption are compared over a patient population for clinical and model-based patient-specific settings calculated by constrained optimization. Approach Brain models for five patients undergoing bilateral DBS were built. Mathematical optimization of activated tissue volume was utilized to calculate stimuli amplitudes, with and without specifying the volumes, where stimulation was not allowed to avoid side effects. Power consumption was estimated using measured impedance values and battery life under both clinical and optimized settings. Results It was observed that clinical settings were generally less aggressive than the ones suggested by unconstrained model-based optimization, especially under asymmetrical stimulation. The DBS settings satisfying the constraints were close to the clinical values. Significance The use of mathematical models to suggest optimal patient-specific DBS settings that observe technological and safety constraints can save time in clinical practice. It appears though that the considered safety constraints based on brain anatomy depend on the patient and further research into it is needed. This work highlights the need of specifying the brain volumes to be avoided by stimulation while optimizing the DBS amplitude, in contrast to minimizing general stimuli overspill, and applies the technique to a cohort of patients. It also stresses the importance of considering power consumption in DBS optimization, since it increases with the square of the stimuli amplitude and also critically affects battery life through pulse frequency and duty cycle.

Background Myositis-specific antibodies (MSA) are autoantibodies that are almost exclusively detected in idiopathic inflammatory myopathies (IIM). This article provides an overview of these autoantibodies and how they can be used clinically to identify subgroups of IIM. Material and methods The article is based on a non-systematic literature review and our own experience. Results MSA can be detected in up to 50 % of patients with IIM. Patients with anti-synthetase antibodies have a constellation of clinical findings termed "the anti-synthetase syndrome", in which interstitial lung disease dominates the clinical picture. Anti-Mi2 antibodies is another myositis-specific antibody. Patients with anti-Mi2 antibodies often have classical dermatomyositis, while the anti-SRP antibody identifies patients with severe myopathy, poor response to treatment with corticosteroids and histological findings of muscle cell necrosis - often lacking inflammatory infiltrates. The newly detected anti-CADMp140 appears to be associated with amyopathic or hypomyopathic dermatomyositis, previously called dermatomyositis sine myositis. Anti-p155 antibodies are most often found in patients who also have cancer. Interpretation Myositis-specific antibodies may be useful for identification of clinical subgroups of IIM and can thereby affect the choice of medical treatment.

The purpose of this validation study was to describe strategies used in postoperative pain assessment among a group of nurses in South Africa. A mixed qualitative and quantitative study was conducted in a 950-bed academic hospital complex. Surgical nurses (n = 12) carried out pain assessments of postoperative patients (n = 36) in pain. Data were collected using detailed interviews and pain intensity was estimated on a visual analogue scale (VAS, 0-10 cm). Nurses used four categories of criteria (a) how the patient looks, (b) what the patient says, (c) the patient's way of talking, and (d) experience of similar circumstances and drew on their past experiences in five different ways: (a) some patients report lower pain intensity than expected, (b) a typology of patients, (c) a focus on listening to patients, (d) what to look for, and (e) what to do for patients were identified. The system of categories described by Sjöström [Sjöström B. Assessing acute postoperative pain. Assessment strategies and quality of clinical experience and professional role. Göteborg: Acta Universitatis Gothoburgensis; 1995] was valid for this sample with an additional category. The different categories seem to be complementary and necessary for assessing pain in others. The findings have implications for professionals who provide care for patients in pain.

The human cannabinoid receptor 1 (CB1), a G protein-coupled receptor (GPCR), translocates its long amino-terminal (N-terminal) domain across the endoplasmic reticulum (ER) membrane in a C-to-N terminal direction. Using the Semliki Forest virus (SFV) expression system, CB1 was expressed in baby hamster kidney (BHK) cells. It was found that a large fraction of the CB1 molecules were N-terminally truncated prior to ER translocation. Truncation was fast and independent of the proteasome. It is concluded that the truncation process might be a way to create a novel type of CB1.

Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a 'biological' hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein-lipid interactions are critical during translocon-mediated membrane insertion.

The Semliki Forest virus (SFV) spike subunits p62 and E1 are made from a common coding unit in the order p62-E1. The proteins are separated by the host signal peptidase upon translocation into the endoplasmic reticulum (ER). Shortly thereafter, p62 and E1 form heterodimers. Heterodimerization preferentially occurs between subunits derived from the same translation product, so-called cis heterodimerization. As the p62 protein has the capacity to leave the ER in the absence of E1, it has been postulated that there exists a retention mechanism for the p62 protein, putatively at or near the translocon, in the ER in order to promote cis heterodimerization (B. U. Barth and H. Garoff, J. Virol. 71: 7857-7865, 1997). Here we show that there exists such a mechanism, that it is at least in part mediated by the ER chaperones calnexin and calreticulin, and that the retention is important for efficient cis heterodimerization.

The purpose of this Master thesis is to deepen understanding of how the concept of information literacy is used within Swedish higher education. The empirical material consists of course syllabi from three different programmes offered at Kristianstad University, Sweden. These are analysed from a sociocultural perspective through qualitative content analysis. Using a data-driven coding frame with different categories, the method helps to define the level of clarity with which information literacy is expressed in the texts. The results of the study reveal that information literacy is seldom explicitly expressed in course syllabi. Information literacy is usually only implied or a potential connection can be discerned. It is concluded that the invisibility of information literacy as such may render it unimportant to students. It is suggested that in a sociocultural perspective, the teaching of information literacy ought to be embedded in the curricula. This requires cooperation between teachers and librarians, something which historically has been difficult to achieve. The analysis also shows that there are connections to information literacy in the syllabi in areas that are highly valued by both professions. These include creative thinking, scientific working processes and the use of information- and communication technology. By shedding light on these similarities, this thesis suggests ways of bringing the two professions closer together.

The popularity and professionalism of female soccer has increased markedly in recent years, with elite players now employed on either a professional or semi-professional basis. The previous review of the physiological demands of female soccer was undertaken two decades ago when the sport was in its relative infancy. Increased research coupled with greater training and competition demands warrants an updated review to consider the effect on physical performance and injury patterns. The physical demands of match-play along with the influence of factors such as the standard of competition, playing position and fatigue have been explored. Total distance covered for elite female players is approximately 10 km, with 1.7 km completed at high speed (>15 kmh(-1)) [corrected].Elite players complete 28% more high-speed running and 24 % more sprinting than moderate-level players. Decrements in high-speed running distance have been reported between and within halves, which may indicate an inability to maintain high-intensity activity. Although the physical capacity of female players is the most thoroughly researched area, comparisons are difficult due to differing protocols. Elite players exhibit maximal oxygen uptake (VO2max) values of 49.4-57.6 mL·kg(-1)·min(-1), Yo Yo Intermittent Endurance test level 2 (YYIE2) scores of 1,774 ± 532 m [mean ± standard deviation (SD)] and 20 m sprint times of 3.17 ± 0.03 s (mean ± SD). Reasons for the increased prevalence of anterior cruciate ligament injuries in females (2-6 times greater than males) are discussed, with anatomical, biomechanical loading and neuromuscular activation differences being cited in the literature. This review presents an in-depth contemporary examination of the applied physiology of the female soccer player.

The ER-Golgi intermediate compartment (ERGIC) marker ERGIC-53 is a mannose-specific membrane lectin operating as a cargo receptor for the transport of glycoproteins from the ER to the ERGIC. Lack of functional ERGIC-53 leads to a selective defect in secretion of glycoproteins in cultured cells and to hemophilia in humans. Beyond its interest as a transport receptor, ERGIC-53 is an attractive probe for studying numerous aspects of protein trafficking in the secretory pathway, including traffic routes, mechanisms of anterograde and retrograde traffic, retention of proteins in the ER, and the function of the ERGIC. Understanding these fundamental processes of cell biology will be crucial for the elucidation and treatment of many inherited and acquired diseases, such as cystic fibrosis, Alzheimer's disease and viral infections.

Soluble secretory proteins are transported from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC) in vesicles coated with COP-II coat proteins. The sorting of secretory cargo into these vesicles is thought to involve transmembrane cargo-receptor proteins. Here we show that a cathepsin-Z-related glycoprotein binds to the recycling, mannose-specific membrane lectin ERGIC-53. Binding occurs in the ER, is carbohydrate- and calcium-ion-dependent and is affected by untrimmed glucose residues. Binding does not, however, require oligomerization of ERGIC-53, although oligomerization is required for exit of ERGIC-53 from the ER. Dissociation of ERGIC-53 occurs in the ERGIC and is delayed if ERGIC-53 is mislocalized to the ER. These results strongly indicate that ERGIC-53 may function as a receptor facilitating ER-to-ERGIC transport of soluble glycoprotein cargo.

Dilysine signals confer localization of type I membrane proteins to the endoplasmic reticulum (ER). According to the prevailing model these signals target proteins to the ER by COP I-mediated retrieval from post-ER compartments, whereas the actual retention mechanism in the ER is unknown. We expressed chimeric membrane proteins with a C-terminal -Lys-Lys-Ala-Ala (KKAA) or -Lys-Lys-Phe-Phe (KKFF) dilysine signal in Lec-1 cells. Unlike KKFF constructs, which had access to post-ER compartments, the KKAA chimeras were localized to the ER by confocal microscopy and were neither processed by cis-Golgi-specific enzymes in vivo nor included into ER-derived transport vesicles in an in vitro budding assay, suggesting that KKAA-bearing proteins are permanently retained in the ER. The ER localization was nonsaturable and exclusively mediated by the dilysine signal because mutating the lysines to alanines led to cell surface expression of the chimeras. Although the KKAA signal avidly binds COP I in vitro, the ER retention by this signal does not depend on intact COP I in vivo because it was not affected in an epsilon-COP-deficient cell line. We propose that dilysine ER targeting signals can mediate ER retention in addition to retrieval.

Exhaust emissions from a heavy-duty diesel vehicle, separated into particulate and semivolatile phases and thereafter fractionated according to polarity, were studied in the adult rat brain after intracranial microinjections using cresyl violet staining and immunohistochemistry. Intrastriatal as well as intrahippocampal injections of particulate fractions III [containing mononitro-polycyclic aromatic hydrocarbon (PAH)], IV (dinitro-PAH and quinones) and V (polar material) and of semivolatile fractions IV and V, in amounts corresponding to a driven length of 19.5 m, caused major lesions with tissue loss and disappearance of immunoreactivity for glial fibrillary acidic protein, tyrosine hydroxylase, and acetylcholine esterase. Particulate fractions I (“light” aliphatic hydrocarbons) and II (“heavy” aliphatic hydrocarbons and PAH) and semivolatile fraction III produced smaller lesions; semivolatile fractions I and II led to lesions equivalent to those of the vehicle dimethyl sulfoxide alone. Microinjected doses of particulate fractions III or IV corresponding to driven lengths of 2.0 and 9.8 m produced a variable lesion. Thus, fractions containing nitro-derivatives of PAH, quinones, and polar material caused the greatest damage after intracranial injections. It is concluded that intracerebral microinjections of fractionated motor vehicle exhausts provide a method for systematic testing of direct neurotoxicity.

Conventionally, assessment of the neurotoxicity of environmental pollutants relies on high-dosage treatment and nonspecific end points. In the present study, the early temporal and regional alterations in the mRNAs of neurotrophins were investigated following subtoxic doses of methylmercury (MeHg) in adult Sprague-Dawley rats using in situ hybridization histochemistry and phosphoimaging evaluation. Decreases in brain-derived neurotrophic (BDNF) mRNA labeling intensities were seen in the dentate gyrus (DG; 44% of controls), and in the CA1 (72% of controls) and CA3c (70% of controls) cell layers of hippocampus after 8 mg MeHg/kg (ip) at 4 h, and at 1 h only in the DG. The decrease in BDNF mRNA expression in the DG was dose-dependent. At 3 d, regional levels had recovered. No significant changes could be detected in mRNA levels of the BDNF high-affinity receptor trkB or neurotrophin-3 mRNA at either 1 h, 4 h, or 3 d. Cresyl violet staining and GFAP immunohistochemistry did not reveal any major neuropathology in hippocampus at 2 wk. Thus, MeHg causes specific downregulation of BDNF mRNA, unlike many other perturbations of central nervous system homeostasis that have been shown to lead to upregulation of this mRNA.