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Abstract Background Health institutions advocate for psychosocial and recovery-oriented interventions alongside pharmacological treatment for severe mental illness. Participatory arts interventions appear promising in promoting personal recovery by fostering connectedness, hope, renegotiation of identity, meaning-making, and empowerment. Despite encouraging findings, however, the evidence base remains thin. Further, results from cognitive literature studies suggest possible impact on parameters of clinical recovery, but this has not been studied in clinical contexts. We developed REWRITALIZE, a structured, recovery-oriented, fifteen-session creative writing group intervention led by a professional author alongside a mental health professional. Participants engage with literary forms, write on them, share their texts, and partake in reflective discussions within a supportive, non-stigmatising environment, designed to promote self-expression, playful experimentation, agency, recognition, participatory meaning-making, renegotiation of identity and social engagement. The aim of this project is to evaluate REWRITALIZE for persons with severe mental illness through a randomised controlled trial (RCT) focusing on personal recovery outcomes. Additionally, an embedded pilot RCT will explore additional outcomes i.e., clinical recovery for a subgroup with schizophrenia spectrum disorders. Methods The RCT is an investigator-initiated, randomised, two-arm, assessor-blinded, multi-center, waiting-list superiority trial involving 300 participants (age > 18) from six psychiatric centers in regions Capital and Zealand in Denmark, randomised to receive either the creative writing intervention combined with standard treatment or standard treatment alone. Assessments will be conducted before and after the intervention and at six months post intervention. The primary outcome is personal recovery at the end of intervention measured with the questionnaire of the process of recovery. Secondary outcomes include other measures of personal recovery, self-efficacy, mentalising, and quality of life. The pilot RCT, integrated within the RCT, will focus on 70 of the participants aged 18–35 with schizophrenia spectrum disorders, evaluating exploratory measures related to perspective-taking, social cognition, cognitive function, psychosocial functioning, and symptom pressure. Discussion This is the first RCT for creative writing groups. It assesses whether REWRITALIZE, as adjunct to standard mental healthcare, is more effective for personal recovery than standard care. If successful, it would provide evidence for the efficacy of REWRITALIZE, potentially enabling its implementation across mental health centers in Denmark. Trial registration Privacy (data protection agency): p-2023–14655. Danish National Center for Ethics: 2313949. Clinicaltrials.gov: NCT06251908. Registration date 02.02.2024.

Abstract Left atrial (LA) epicardial adipose tissue (EAT) and wall fibrosis are both proven to contribute to the pathogenesis and progression of atrial fibrillation (AF). The theory of LA wall fibrosis induction by local EAT infiltration, paracrine secretions, and activation of the inflammatory process is strongly advocated, but the imaging evidence for anatomical proximity of the two tissue types and its association to AF stage is lacking. Accordingly, the aim of the study was to analyse the spatial overlap between LA EAT and adjacent wall fibrosis using 3D Dixon water-fat separated late gadolinium enhancement (LGE-Dixon) MRI and correlate the findings with the clinical AF stage. Forty-two AF patients (18 paroxysmal, 10 persistent, and 14 permanent) and nine non-AF patients were scanned. The permanent AF patients had greater LA volume and EAT than the paroxysmal group. The LA fibrosis area showed the same trend. The LA EAT-fibrosis overlap area was small and there was no significant difference between the three AF stages. There was no significant relationship between LA EAT- fibrosis overlap area and AF type. The findings shed light on the complex interplay between LA fibrosis and EAT during the progression from paroxysmal to permanent AF.

This paper analyzes policy discussion regarding key developments in the national organization of the Swedish academic career during the period 1955–2020. In the 1950s, the academic career was highly regulated and state-planned with a few exclusive academic positions. In 2020, it has become essentially deregulated with universities themselves establishing employment positions. Four key developments are identified: the emergence of parallel careers, the expansion of external research funding, the dramatic increase in professors, and the deregulation of national policy on academic careers. The national policy discussions underpinning these developments are analysed with the help of a theoretical framework for explaining different types of institutional change. The paper shows that changes to the Swedish academic career were undertaken gradually over time, mainly by the layering of new rules over or alongside existing ones as a supplement. In addition, the paper shows that some problems with the academic career have been discussed repeatedly and that even where solutions have been set out, the problems seem to persist.

Abstract Strength, ductility, and failure properties of metals are tailored by plastic deformation routes. Predicting these properties requires modeling of the structural dynamics and stress evolution taking place on several length scales. Progress has been hampered by a lack of representative 3D experimental data at industrially relevant degrees of deformation. We present an X-ray imaging based 3D mapping of an aluminum polycrystal deformed to the ultimate tensile strength (32% elongation). The extensive dataset reveals significant intra-grain stress variations (36 MPa) up to at least half of the inter-grain variations (76 MPa), which are dominated by grain orientation effects. Local intra-grain stress concentrations are candidates for damage nucleation. Such data are important for models of structure-property relations and damage.

Definite diagnosis of Lyme neuroborreliosis (LNB) requires investigation of serum and cerebrospinal fluid (CSF). Thus, lumbar puncture is necessary, and requires administration of sedating drugs in children. This study aimed to investigate if a pattern of different inflammatory biomarkers in serum could contribute to the selection of children for lumbar puncture in suspected LNB.Patients were included from a cohort of children who was previously investigated for LNB including serum and CSF sampling during the years 2010–2014. The multiplex proximity extension assay (PEA) inflammation panel Target 96 (Olink Bioscience, Uppsala, Sweden) was used to examine 92 biomarkers in serum.Based on the presence of CSF pleocytosis and Borrelia-specific antibodies, patients were divided into a definite LNB group (n=61) and a non-LNB control group (n=58). Following PEA and statistical analysis with multivariate logistic regression, five biomarkers remained significant (p < 0.001), which were included in a calculation of protein index. The index biomarkers were CST5, IL-15RA, CXCL10, DNER and CX3CL1. A receiver operating characteristic curve was constructed from the index, which showed an 80 % sensitivity and 81 % specificity. Area under the curve was 0.889.We offer evidence that, with further refinements, patterns of serum biomarkers might help identify those children more or less likely to have LNB, perhaps ultimately decreasing the need for lumbar punctures.

Abstract Background Biologgers have contributed greatly to studies of animal movement, behaviours and physiology. Accelerometers, among the various on-board sensors of biologgers, have mainly been used for animal behaviour classification and energy expenditure estimation. However, a general principle for the combined sampling duration and frequency for different taxa is lacking. In this study, we evaluated whether Nyquist–Shannon sampling theorem applies to accelerometer-based classification of animal behaviour and energy expenditure approximation. To evaluate the influence of accelerometer sampling frequency on behaviour classification, we annotated accelerometer data from seven European pied flycatchers (Ficedula hypoleuca) freely moving in aviaries. We also used simulated data to systematically evaluate the combined effect of sampling duration and sampling frequency on the performance of estimating signal frequency and amplitude. Results We found that a sampling frequency higher than Nyquist frequency at 100 Hz was needed to classify fast, short-burst behavioural movements of pied flycatcher, such as swallowing food with a mean frequency of 28 Hz. In contrast, high frequency movements with longer durations such as flight could be characterized adequately using much lower sampling frequency of 12.5 Hz. To identify rapid transient prey catching manoeuvres within these flight bouts, again a high frequency sampling at 100 Hz was needed. For both the experimental data of the flycatchers and the simulated data, the combination of sampling frequency and sampling duration affected the accuracy of signal frequency and amplitude estimation. For long sampling durations, the sampling frequency equal to the Nyquist frequency was adequate for accurate signal frequency and amplitude estimation. Accuracy declined with decreasing sampling duration, especially for signal amplitude estimation with up to 40% standard deviation of normalized amplitude difference. To accurately estimate signal amplitude at low sampling duration, a sampling frequency of four times the signal frequency was necessary (two times the Nyquist frequency). Conclusions The appropriate sampling frequency of accelerometers depends on the objective of the specific study and the characteristics of the behaviour. For studies with no constraints on device battery and storage, a sampling frequency of at least two times the Nyquist frequency will achieve relative optimal representative of signal information (i.e., frequency and amplitude). For classification and energy expenditure estimation of short-burst behaviours, 1.4 times the Nyquist frequency of behaviour is required.

As part of the NorthTick project, co-funded by the European Union through the European Regional Development Fund and the North Sea Region Programme, specialists in the field of tick-borne diseases from seven North Sea countries co-operated with patient organisations and governmental health care institutions to provide this comprehensive overview of diagnostics and treatment recommendations in the region for Lyme borreliosis, Borrelia miyamotoi infection, tick-borne encephalitis, human granulocytic anaplasmosis, rickettsiosis, neoehrlichiosis and babesiosis. The main conclusion is that the recommendations in these northern countries are essentially the same, with very few differences. This overview presents the current diagnostics and provides useful clinical guidance.

Background. Patients undergoing breast surgery are at risk of severe postoperative pain. Several opioid-sparing strategies exist to alleviate this condition. Regional anesthesia has long been a part of perioperative pain management for these patients. Aim. This randomized study examined the benefits of interpectoral and pectoserratus plane block (IPP/PSP), also known as pectoralis nerve plain block, compared with advanced local anesthetic infiltration. Methods. We analyzed 57 patients undergoing partial mastectomy with sentinel node dissection. They received either an ultrasound-guided IPP/PSP block performed preoperatively by an anesthetist or local anesthetic infiltration performed by the surgeon before and during the surgery. Results. Pain measured with the numerical rating scale (NRS) indicated no statistically significant difference between the groups (IPP/PSP 1.67 vs. infiltration 1.97; p value 0.578). Intraoperative use of fentanyl was significantly lower in the IPP/PSP group (0.18 mg vs 0.21 mg; p value 0.041). There was no statistically significant difference in the length of stay in the PACU (166 min vs 175 min; p value 0.51). There were no differences in reported postoperative nausea and vomiting (PONV) between the groups. The difference in postoperative use of oxycodone in the PACU (p value 0.7) and the use of oxycodone within 24 hours postoperatively (p value 0.87) was not statistically significant. Conclusions. Our study showed decreased intraoperative opioid use in the IPP/PSP group and no difference in postoperative pain scores up to 24 hours. Both groups reported low postoperative pain scores. This trial is registered with NCT04824599.

Abstract Lyme neuroborreliosis (LNB) is associated with increased levels of pro-inflammatory cytokines and chemokines in the cerebrospinal fluid (CSF). Residual symptoms after antibiotic treatment can have deleterious effects on patients and knowledge regarding the pathogenesis linked to prolonged recovery is lacking. In this prospective follow-up study, we investigated the B cell-associated and T helper (Th) cell-associated immune responses in well-characterized patients with LNB and controls. The aims were to assess the kinetics of selected cytokines and chemokines involved in the inflammatory response and to identify potential prognostic markers. We investigated 13 patients with LNB according to a standardized clinical protocol before antibiotic treatment and after 1, 6 and 12 months of follow-up. CSF and blood samples were obtained at baseline and after 1 month. As controls, we used CSF samples from 37 patients who received spinal anesthesia during orthopedic surgery. The CSF samples were analyzed for CXCL10 (Th1-related), CCL22 (Th2-related) and IL-17A, CXCL1 and CCL20 (Th17-related), as well as for the B cell-related cytokines of a proliferation-inducing ligand (APRIL), B cell-activating factor (BAFF) and CXCL13. The CSF levels of all the cytokines and chemokines, with the exception of APRIL, were significantly higher at baseline in patients with LNB compared with controls. All the cytokines and chemokines, except for IL-17A were significantly reduced at 1-month follow-up. Patients with quick recovery ( 6 months (n = 7) had significantly higher levels of IL-17A at the one-month follow-up. No other cytokines or chemokines were associated with prolonged recovery. Dominating residual symptoms were fatigue, myalgia, radiculitis and/or arthralgia. In this prospective follow-up study of patients with LNB, we found significantly lower levels of CCL20 in those who recovered rapidly, and increased levels of IL-17A in patients with delayed recovery post-treatment. Our findings indicate persistent Th17-driven inflammation in the CSF, possibly contributing to a longer convalescence, and suggest IL-17A and CCL20 as potential biomarker candidates for patients with LNB.

Recently, a number of inbreeding cases have surfaced that have fuelled public criticism of recruitment practices and the lack of mobility in the Swedish higher education sector. This study focuses on recruitment practices at Swedish universities, particularly the divergence between what seems to be a practice of hiring internal candidates and a policy aiming at increasing mobility. The empirical material comprises 14 interviews with heads of departments at a selection of Swedish universities. Institutional logics are used as an analytical framework. It is found that academic recruitment is situated in a tangle of different practices and ideals comprising six logics: state, academic, managerial, market, community and family. Heads of departments show that recruitment practices are the result of several considerations where, for example, meritocracy, bureaucracy and loyalty do not always pull in the same direction.

Abstract Background About two-thirds of the in-hospital deaths after out-of-hospital cardiac arrests (OHCA) are a consequence of anoxic brain injuries, which are due to hypoperfusion of the brain during the cardiac arrests. Being able to monitor cerebral perfusion during cardiopulmonary resuscitation (CPR) is desirable to evaluate the effectiveness of the CPR and to guide further decision making and prognostication. Methods Two different devices were used to measure regional cerebral oxygen saturation (rSO2): INVOS™ 5100 (Medtronic, Minneapolis, MN, USA) and Root® O3 (Masimo Corporation, Irvine, CA, USA). At the scene of the OHCA, advanced life support (ALS) was immediately initiated by the Emergency Medical Services (EMS) personnel. Sensors for measuring rSO2 were applied at the scene or during transportation to the hospital. rSO2 values were documented manually together with ETCO2 (end tidal carbon dioxide) on a worksheet specially designed for this study. The study worksheet also included a questionnaire for the EMS personnel with one statement on usability regarding potential interference with ALS. Results Twenty-seven patients were included in the statistical analyses. In the INVOS™5100 group (n = 13), the mean rSO2 was 54% (95% CI 40.3–67.7) for patients achieving a return of spontaneous circulation (ROSC) and 28% (95% CI 12.3–43.7) for patients not achieving ROSC (p = 0.04). In the Root® O3 group (n = 14), the mean rSO2 was 50% (95% CI 46.5–53.5) and 41% (95% CI 36.3–45.7) (p = 0.02) for ROSC and no ROSC, respectively. ETCO2 values were not statistically different between the groups. The EMS personnel graded the statement of interference with ALS to a median of 2 (IQR 1–6) on a 10-point Numerical Rating Scale. Conclusion Our results suggest that both INVOS™5100 and ROOT® O3 can distinguish between ROSC and no ROSC in OHCA, and both could be used in the pre-hospital setting and during transport with minimal interference with ALS.

We report 2 cases of Spiroplasma ixodetis infection in an immunocompetent patient and an immunocompromised patient who had frequent tick exposure. Fever, thrombocytopenia, and increased liver aminotransferase levels raised the suspicion of anaplasmosis, but 16S rRNA PCR and Sanger sequencing yielded a diagnosis of spiroplasmosis. Both patients recovered after doxycycline treatment.

• We developed an extracorporeal cardiopulmonary resuscitation (ECPR) selection model (the PRognostic Evaluation of ECPR [Pre-ECPR] score) based on ECPR outcome. • The score combines weighted predictors and gives a probability of a good outcome. • In cross-validation, the score performs better than the Extracorporeal Life Support Organization ECPR selection criteria. • At 100% sensitivity, the Pre-ECPR score achieved a 40% positive predictive value. • A web application facilitates external validation and refinement of the Pre-ECPR score. Extracorporeal cardiopulmonary resuscitation (ECPR) can save patients with refractory cardiac arrest; however, according to recent meta-analyses, only 20% of patients achieve favorable outcomes (Modified Rankin Scale 0-3). We aimed to develop and validate an ECPR prediction model to improve patient selection. Prognostic model development and internal validation study. Single-center study. All 120 normothermic ECPR patients treated at Sahlgrenska University Hospital between January 2010 and October 2021. None. Multivariable logistic regression was used to develop the PRognostic Evaluation of ECPR (Pre-ECPR) score. Model performance was assessed through the area under curve (AUC) and compared with the Extracorporeal Life Support Organization (ELSO) "Example of selection criteria for ECPR" for 1-year survival with favorable outcomes. The positive predictive value (PPV) was calculated. Favorable outcomes occurred in 27.5% of the patients. The Pre-ECPR score, incorporating age, no-flow/initial rhythm (a composite variable), total cardiac arrest time, signs of life, pupil dilation, regional cerebral oxygen saturation, arterial pH, and end-tidal CO 2 , demonstrated an AUC of 0.87 (95% confidence interval [CI] 0.77-0.93). In internal cross-validation, the AUC of 0.79 (95% CI 0.67-0.88) significantly outperformed the ELSO criteria AUC of 0.63 (95% CI 0.54-0.72, p = 0.012). Pre-ECPR score probabilities >6.4% showed 100% sensitivity and a PPV of 40.5% for favorable outcomes. The Pre-ECPR score combines multiple weighted predictors to provide a single balanced probability of favorable outcomes in ECPR patient selection. In cross-validation, it demonstrated significantly more favorable discriminatory performance than that of the ELSO criteria. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives Lyme serology does not readily discriminate an active Lyme borreliosis (LB) from a previous Borrelia infection or exposure. Here, we aimed to investigate a large number of immunological protein biomarkers to search for an immunological pattern typical for active LB, in contrast to patterns found in healthy blood donors, a proportion of whom were previously exposed to Borrelia. Methods Serum samples from well-characterised adult patients with ongoing LB and healthy blood donors were included and investigated using a proximity extension assay (provided by Olink®) by which 92 different immune response-related human protein biomarkers were analysed simultaneously. Results In total, 52 LB patients and 75 healthy blood donors were included. The blood donors represented both previouslyBorreliaexposed (n = 34) and not exposed (n = 41) based on anti-Borreliaantibody status. Ten of the examined 92 proteins differed between patients and blood donors and were chosen for further logistic regression (pConclusions The results from this study suggest that there is an immunological protein pattern that can distinguish a present Borrelia infection from a previous exposure as well as anti-Borrelia antibody negative blood donors. Although this method is not adapted for routine clinical use at this point, the possibility is interesting and may open new diagnostic opportunities improving the laboratory diagnostics of LB.

BackgroundBalanced transfusions, including platelets, are critical for bleeding patients to maintain hemostasis. Many rural hospitals have no or limited platelet inventory, with several hours of transport time from larger hospitals. This study aimed to evaluate the feasibility of using cryopreserved platelets that can be stored for years, in remote hospitals with no or limited platelet inventory.Material and methodsThree remote hospitals participated in a prospective study including adult bleeding patients where platelet transfusions were indicated. Cryopreserved platelets were prepared in a university hospital, concentrated in 10 ml, transported on dry ice, and stored at −80°C at the receiving hospital. At request, the concentrated platelet units were thawed and diluted in fresh frozen plasma. The indications, blood transfusion needs, and laboratory parameters pre- and post-transfusion, as well as logistics, such as time from request to transfusion and work efforts in preparing cryopreserved platelets, were evaluated.ResultsTwenty-three bleeding patients were included. Nine patients (39%) were treated for gastrointestinal bleeding, five (22%) for perioperative bleeding, and four (17%) for trauma bleeding. The transfusion needs were 4.9 ± 3.3 red blood cell units, 3.2 ± 2.3 plasma units, and 1.9 ± 2.2 platelet units, whereof cryopreserved were 1.5 ± 1.1 (mean ± SD). One patient had a mild allergic reaction. We could not show the difference in laboratory results between pre- and post-transfusion of the cryopreserved units in the bleeding patients. The mean time from the order of cryopreserved platelets to transfusion was 64 min, with a range from 25 to 180 min.ConclusionCryopreserved platelets in remote hospitals are logistically feasible in the treatment of bleeding. The ability to have platelets in stock reduces the time to platelet transfusion in bleeding patients where the alternative often is many hours delay. Clinical effectiveness and safety previously shown in other studies are supported in this small feasibility study.

IntroductionAfter more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.MethodsHere, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.ResultsWe found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.ConclusionBy exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.

Abstract Background Our aim was to introduce damaged red blood cells (RBCs) as a tool for haemodynamic provocation in rats, hypothesised to cause decreased cerebral blood flow (CBF) and prolonged water capillary transfer time (CTT), and to investigate whether expected changes in CBF could be observed and if haemodynamic alterations were reflected by the CTT metric. Methods Damaged RBCs exhibiting a mildly reduced deformability were injected to cause aggregation of RBCs. Arterial spin labelling (ASL) magnetic resonance imaging experiments were performed at 9.4 T. Six datasets (baseline plus five datasets after injection) were acquired for each animal in a study group and a control group (13 and 10 female adult Wistar rats, respectively). For each dataset, ASL images at ten different inversion times were acquired. The CTT model was adapted to the use of a measured arterial input function, implying the use of a realistic labelling profile. Repeated measures ANOVA was used (alpha error = 0.05). Results After injection, significant differences between the study group and control group were observed for relative CBF in white matter (up to 20 percentage points) and putamen (up to 18–20 percentage points) and for relative CTT in putamen (up to 35–40 percentage points). Conclusions Haemodynamic changes caused by injection of damaged RBCs were observed by ASL-based CBF and CTT measurements. Damaged RBCs can be used as a tool for test and validation of perfusion imaging modalities. CTT model fitting was challenging to stabilise at experimental signal-to-noise ratio levels, and the number of free parameters was minimised.

The Multimapping technique was recently proposed for simultaneous myocardial T1 and T2 mapping. In this study, we evaluate its correlation with clinical reference mapping techniques in patients with a range of cardiovascular diseases (CVDs) and compare image quality and inter- and intra-observer repeatability. Multimapping consists of an ECG-triggered, 2D single-shot bSSFP readout with inversion recovery and T2 preparation modules, acquired across 10 cardiac cycles. The sequence was implemented at 1.5T and compared to clinical reference mapping techniques, modified Look-Locker inversion recovery (MOLLI) and T2 prepared bSSFP with four echo times (T2bSSFP), and compared in 47 patients with CVD (of which 44 were analyzed). In diseased myocardial segments (defined as the presence of late gadolinium enhancement), there was a high correlation between Multimapping and MOLLI for native myocardium T1 (r2 = 0.73), ECV (r2 = 0.91), and blood T1 (r2 = 0.88), and Multimapping and T2bSSFP for native myocardial T2 (r2 = 0.80). In healthy myocardial segments, a bias for native T1 (Multimapping = 1,116 ± 21 ms, MOLLI = 1,002 ± 21, P < 0.001), post-contrast T1 (Multimapping = 479 ± 31 ms, MOLLI = 426 ± 27 ms, 0.001), ECV (Multimapping = 21.5 ± 1.9%, MOLLI = 23.7 ± 2.3%, P = 0.001), and native T2 (Multimapping = 48.0 ± 3.0 ms, T2bSSFP = 53.9 ± 3.5 ms, P < 0.001) was observed. The image quality for Multimapping was scored as higher for all mapping techniques (native T1, post-contrast T1, ECV, and T2bSSFP) compared to the clinical reference techniques. The inter- and intra-observer agreements were excellent (intraclass correlation coefficient, ICC > 0.9) for most measurements, except for inter-observer repeatability of Multimapping native T1 (ICC = 0.87), post-contrast T1 (ICC = 0.73), and T2bSSFP native T2 (ICC = 0.88). Multimapping shows high correlations with clinical reference mapping techniques for T1, T2, and ECV in a diverse cohort of patients with different cardiovascular diseases. Multimapping enables simultaneous T1 and T2 mapping and can be performed in a short breath-hold, with image quality superior to that of the clinical reference techniques.

IntroductionTo develop and test the feasibility of free-breathing (FB), high-resolution quantitative first-pass perfusion cardiac MR (FPP-CMR) using dual-echo Dixon (FOSTERS; Fat-water separation for mOtion-corrected Spatio-TEmporally accelerated myocardial peRfuSion).Materials and MethodsFOSTERS was performed in FB using a dual-saturation single-bolus acquisition with dual-echo Dixon and a dynamically variable Cartesian k-t undersampling (8-fold) approach, with low-rank and sparsity constrained reconstruction, to achieve high-resolution FPP-CMR images. FOSTERS also included automatic in-plane motion estimation and T2* correction to obtain quantitative myocardial blood flow (MBF) maps. High-resolution (1.6 x 1.6 mm2) FB FOSTERS was evaluated in eleven patients, during rest, against standard-resolution (2.6 x 2.6 mm2) 2-fold SENSE-accelerated breath-hold (BH) FPP-CMR. In addition, MBF was computed for FOSTERS and spatial wavelet-based compressed sensing (CS) reconstruction. Two cardiologists scored the image quality (IQ) of FOSTERS, CS, and standard BH FPP-CMR images using a 4-point scale (1–4, non-diagnostic – fully diagnostic).ResultsFOSTERS produced high-quality images without dark-rim and with reduced motion-related artifacts, using an 8x accelerated FB acquisition. FOSTERS and standard BH FPP-CMR exhibited excellent IQ with an average score of 3.5 ± 0.6 and 3.4 ± 0.6 (no statistical difference, p > 0.05), respectively. CS images exhibited severe artifacts and high levels of noise, resulting in an average IQ score of 2.9 ± 0.5. MBF values obtained with FOSTERS presented a lower variance than those obtained with CS.DiscussionFOSTERS enabled high-resolution FB FPP-CMR with MBF quantification. Combining motion correction with a low-rank and sparsity-constrained reconstruction results in excellent image quality.

Abstract Dynamic contrast-enhanced quantitative first-pass perfusion using magnetic resonance imaging enables non-invasive objective assessment of myocardial ischemia without ionizing radiation. However, quantification of perfusion is challenging due to the non-linearity between the magnetic resonance signal intensity and contrast agent concentration. Furthermore, respiratory motion during data acquisition precludes quantification of perfusion. While motion correction techniques have been proposed, they have been hampered by the challenge of accounting for dramatic contrast changes during the bolus and long execution times. In this work we investigate the use of a novel free-breathing multi-echo Dixon technique for quantitative myocardial perfusion. The Dixon fat images, unaffected by the dynamic contrast-enhancement, are used to efficiently estimate rigid-body respiratory motion and the computed transformations are applied to the corresponding diagnostic water images. This is followed by a second non-linear correction step using the Dixon water images to remove residual motion. The proposed Dixon motion correction technique was compared to the state-of-the-art technique (spatiotemporal based registration). We demonstrate that the proposed method performs comparably to the state-of-the-art but is significantly faster to execute. Furthermore, the proposed technique can be used to correct for the decay of signal due to T2* effects to improve quantification and additionally, yields fat-free diagnostic images.

Abstract Background There is an increased interest in quantifying and characterizing epicardial fat which has been linked to various cardiovascular diseases such as coronary artery disease and atrial fibrillation. Recently, three-dimensional single-phase Dixon techniques have been used to depict the heart and to quantify the surrounding fat. The purpose of this study was to investigate the merits of a new high-resolution cine 3D Dixon technique for quantification of epicardial adipose tissue and compare it to single-phase 3D Dixon in patients with cardiovascular disease. Methods Fifteen patients referred for clinical CMR examination of known or suspected heart disease were scanned on a 1.5 T scanner using single-phase Dixon and cine Dixon. Epicardial fat was segmented by three readers and intra- and inter-observer variability was calculated per slice. Cine Dixon segmentation was performed in the same cardiac phase as single-phase Dixon. Subjective image quality assessment of water and fat images were performed by three readers using a 4-point Likert scale (1 = severe; 2 = significant; 3 = mild; 4 = no blurring of cardiac structures). Results Intra-observer variability was excellent for cine Dixon images (ICC = 0.96), and higher than single-phase Dixon (ICC = 0.92). Inter-observer variability was good for cine Dixon (ICC = 0.76) and moderate for single-phase Dixon (ICC = 0.63). The intra-observer measurement error (mean ± standard deviation) per slice for cine was − 0.02 ± 0.51 ml (− 0.08 ± 0.4%), and for single-phase 0.39 ± 0.72 ml (0.18 ± 0.41%). Inter-observer measurement error for cine was 0.46 ± 0.98 ml (0.11 ± 0.46%) and for single-phase 0.42 ± 1.53 ml (0.17 ± 0.47%). Visual scoring of the water image yielded median of 2 (interquartile range = [Q3-Q1] 2–2) for cine and median of 3 (interquartile range = 3–2) for single-phase (P

Clonal evolution and heterogeneity has strong implications for treatment response in acute myeloid leukemia. Here, the authors use patient derived in vivo modelling to highlight the complex clonal and evolutionary dynamics underpinning acute myeloid leukemia progression.

This paper applies the Red Queen theory to explain how organizations utilize various sourcing arrangements in order to compete in an evolutionary arms race where only the strongest competitors will survive. The case study incorporates competition, and views sourcing strategies as a means to improve the firm’s viability to survive competition in the marketplace. The study begins by positioning the Red Queen theory within the sourcing literature. It subsequently applies the framework to a case study of SAP AG to illustrate how sourcing strategies have changed over time in response to the logic of competition. The case study reveals that (a) organizations are adaptive systems and capable of learning to make strategic changes pertaining to sourcing arrangements; (b) organizations select the terms on which they want to compete by developing certain capabilities within the firm; (c) organizations are reflexive and over time develop competitive hysteresis which allows them to become stronger competitors. In the case of SAP AG, various sourcing arrangements were selected over its 40-year history to respond to technological and market changes.

Arthroplasty surgery is a common procedure that significantly improves quality of life. The most feared complication is prosthetic joint infection (PJI), which occurs more often following revision surgery. Staphylococci are the most prevalent bacteria in PJIs, although many other pathogens have been reported. We describe a case of PJI in a 75-year-old farmer following revision surgery caused by Corynebacterium striatum, an unusual agent which normally occurs in the normal human skin microbiota with perceived low pathogenicity. Following a cemented right-sided total hip arthroplasty in 2006, a one-stage revision due to an osteolytic process in the right femur took place in 2020 with negative intraoperative tissue cultures. Three weeks later, the patient presented a fulminant infection which was treated with debridement, antibiotics, and implant retention (DAIR). Tissue biopsies showed C. striatum in 6/6 samples including small colony variants. Genome sequencing showed that all isolates differed by ≤6 SNPs with the same gene content related to resistance (tet(W) and erm(X)). The patient was sequentially treated with vancomycin, linezolid, and daptomycin, but due to side effects, treatment was changed to 12 weeks of dalbavancin as a 1000 mg loading dose followed by 500 mg intravenously/week. Impaired renal function during vancomycin treatment was normalized, and >1 year after finishing antibiotic treatment the outcome was still favourable. In conclusion, a case of a fulminant early post-interventional PJI due to C. striatum was successfully treated with DAIR and long-term dalbavancin therapy without any adverse reactions.

Abstract Objectives The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization. Trial design Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority. Participants Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden. Intervention and comparator Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19. Main outcomes The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion). Randomisation Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + “standard of care”: “standard of care”). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) Blinding (masking) This is an open-label trial. Numbers to be randomised (sample size) The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total. Trial Status The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021. Trial registration Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Academic career systems have been in focus lately as a means to attract talented researchers and teachers. In this paper, we compare tenure tracks at three Swedish universities. The analysis relies on qualitative data, including interviews and policy documents, and revolves around three questions: How is the tenure track designed? What were the drivers behind the new tenure track? How is the tenure track designed to handle emerging tensions? We identify three common drivers and rationales: transparency, recruitment of early career researchers and long-term retention of staff. The article ends with a discussion of important considerations that were made when introducing the tenure track. The considerations derive from the tensions between research and teaching, between scope and funding and between the needs of the institution and the rights of the individual. The results are important in an increasingly competitive higher education sector aiming to construct and implement attractive career systems.

Background: For the most important and well-known infections spread by Ixodes ticks, Lyme borreliosis (LB) and tick-borne encephalitis (TBE), there are recommendations for diagnosis and management available from several health authorities and professional medical networks. However, other tick-borne microorganisms with potential to cause human disease are less known and clear recommendations on diagnosis and management are scarce. Therefore, we performed a systematic review of published studies and reviews focusing on evaluation of laboratory methods for clinical diagnosis of human tick-borne diseases (TBDs), other than acute LB and TBE. The specific aim was to evaluate the scientific support for laboratory diagnosis of human granulocytic anaplasmosis, rickettsiosis, neoehrlichiosis, babesiosis, hard tick relapsing fever, tularemia and bartonellosis, as well as tick-borne co-infections and persistent LB in spite of recommended standard antibiotic treatment.Methods: We performed a systematic literature search in 11 databases for research published from 2007 through 2017, and categorized potentially relevant references according to the predefined infections and study design. An expert group assessed the relevance and eligibility and reviewed the articles according to the QUADAS (diagnostic studies) or AMSTAR (systematic reviews) protocols, respectively. Clinical evaluations of one or several diagnostic tests and systematic reviews were included. Case reports, non-human studies and articles published in other languages than English were excluded.Results: A total of 48 studies fulfilled the inclusion criteria for evaluation. The majority of these studies were based on small sample sizes. There were no eligible studies for evaluation of tick-borne co-infections or for persistent LB after antibiotic treatment.Conclusions: Our findings highlight the need for larger evaluations of laboratory tests using clinical samples from well-defined cases taken at different time-points during the course of the diseases. Since the diseases occur at a relatively low frequency, single-center cross-sectional studies are practically not feasible, but multi-center case control studies could be a way forward.

Animals flying in the wild often show remarkable abilities to negotiate obstacles and narrow openings in complex environments. Impressive as these abilities are, this must result in costs in terms of impaired flight performance. In this study, I used a budgerigar as a model for studying these costs. The bird was filmed in stereo when flying through a wide range of gap widths from well above wingspan down to a mere 1/4 of wingspan. Three-dimensional flight trajectories were acquired and speed, wingbeat frequency and accelerations/decelerations were calculated. The bird used two different wing postures to get through the gaps and could use very small safety margins (down to 6 mm on either side) but preferred to use larger when gap width allowed. When gaps were smaller than wingspan, flight speed was reduced with reducing gap width down to half for the smallest and wingbeat frequency was increased. I conclude that flying through gaps potentially comes with multiple types of cost to a bird of which the main may be: (i) reduced flight speed increases the flight duration and hence the energy consumption to get from point A to B, (ii) the underlying U-shaped speed to power relationship means further cost from reduced flight speed, and associated with it (iii) elevated wingbeat frequency includes a third direct cost.

We report 2 human cases of Borrelia miyamotoi disease diagnosed in Sweden, including 1 case of meningitis in an apparently immunocompetent patient. The diagnoses were confirmed by 3 different independent PCR assays and DNA sequencing from cerebrospinal fluid, supplemented by serologic analyses.

Abstract Aims To investigate the use of respiratory motion compensation using image-based navigation (iNAV) with constant respiratory efficiency using single end-expiratory thresholding (CRUISE) for coronary magnetic resonance angiography (CMRA), and compare it to the conventional diaphragmatic navigator (dNAV) in paediatric patients with congenital or suspected heart disease. Methods iNAV allowed direct tracking of the respiratory heart motion and was generated using balanced steady state free precession startup echoes. Respiratory gating was achieved using CRUISE with a fixed 50% efficiency. Whole-heart CMRA was acquired with 1.3 mm isotropic resolution. For comparison, CMRA with identical imaging parameters were acquired using dNAV. Scan time, visualization of coronary artery origins and mid-course, imaging quality and sharpness was compared between the two sequences. Results Forty patients (13 females; median weight: 44 kg; median age: 12.6, range: 3 months–17 years) were enrolled. 25 scans were performed in awake patients. A contrast agent was used in 22 patients. The scan time was significantly reduced using iNAV for awake patients (iNAV 7:48 ± 1:26 vs dNAV 9:48 ± 3:11, P = 0.01) but not for patients under general anaesthesia (iNAV = 6:55 ± 1:50 versus dNAV = 6:32 ± 2:16; P = 0.32). In 98% of the cases, iNAV image quality had an equal or higher score than dNAV. The visual score analysis showed a clear difference, favouring iNAV (P = 0.002). The right coronary artery and the left anterior descending vessel sharpness was significantly improved (iNAV: 56.8% ± 10.1% vs dNAV: 53.7% ± 9.9%, P

The genus Borrelia encompasses bacterial pathogens that can cause Lyme borreliosis (LB) and relapsing fever (RF) [...]