Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization.

T cell stimulation remodels the latently HIV-1 infected cell population by differential activation of proviral chromatin.

The reservoir of latently HIV-1 infected cells is heterogeneous. To achieve an HIV-1 cure, the reservoir of activatable proviruses must be eliminated while permanently silenced proviruses may be tolerated. We have developed a method to assess the proviral nuclear microenvironment in single cells. In latently HIV-1 infected cells, a zinc finger protein tethered to the HIV-1 promoter produced a fluorescent signal as a protein of interest came in its proximity, such as the viral transactivator Tat when recruited to the nascent RNA. Tat is essential for viral replication. In these cells we assessed the proviral activation and chromatin composition. By linking Tat recruitment to proviral activity, we dissected the mechanisms of HIV-1 latency reversal and the consequences of HIV-1 production. A pulse of promoter-associated Tat was identified that contrasted to the continuous production of viral proteins. As expected, promoter H3K4me3 led to substantial expression of the provirus following T cell stimulation. However, the activation-induced cell cycle arrest and death led to a surviving cell fraction with proviruses encapsulated in repressive chromatin. Further, this cellular model was used to reveal mechanisms of action of small molecules. In a proof-of-concept study we determined the effect of modifying enhancer chromatin on HIV-1 latency reversal. Only proviruses resembling active enhancers, associated with H3K4me1 and H3K27ac and subsequentially recognized by BRD4, efficiently recruited Tat upon cell stimulation. Tat-independent HIV-1 latency reversal of unknown significance still occurred. We present a method for single cell assessment of the microenvironment of the latent HIV-1 proviruses, used here to reveal how T cell stimulation modulates the proviral activity and how the subsequent fate of the infected cell depends on the chromatin context.

PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin at the Lamina Promote Oscillating Transcription.

Transcriptionally active and inactive chromatin domains tend to segregate into separate sub-nuclear compartments to maintain stable expression patterns. However, here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). The interactome is regulated by PARP1 and its co-factor CTCF. They not only mediate chromatin fiber interactions but also promote the recruitment of circadian genes to the lamina. Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by olaparib, or downregulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity.

Chromatin maturation of the HIV-1 provirus in primary resting CD4+ T cells.

Human immunodeficiency virus type 1 (HIV-1) infection is a chronic condition, where viral DNA integrates into the genome. Latently infected cells form a persistent, heterogeneous reservoir that at any time can reactivate the integrated HIV-1. Here we confirmed that latently infected cells from HIV-1 positive study participants exhibited active HIV-1 transcription but without production of mature spliced mRNAs. To elucidate the mechanisms behind this we employed primary HIV-1 latency models to study latency establishment and maintenance. We characterized proviral transcription and chromatin development in cultures of resting primary CD4+ T-cells for four months after ex vivo HIV-1 infection. As heterochromatin (marked with H3K9me3 or H3K27me3) gradually stabilized, the provirus became less accessible with reduced activation potential. In a subset of infected cells, active marks (e.g. H3K27ac) and elongating RNAPII remained detectable at the latent provirus, despite prolonged proviral silencing. In many aspects, latent HIV-1 resembled an active enhancer in a subset of resting cells. The enhancer chromatin actively promoted latency and the enhancer-specific CBP/P300-inhibitor GNE049 was identified as a new latency reversal agent. The division of the latent reservoir according to distinct chromatin compositions with different reactivation potential enforces the notion that even though a relatively large set of cells contains the HIV-1 provirus, only a discrete subset is readily able to reactivate the provirus and spread the infection.

Phase-contrast enhanced synchrotron micro-tomography of human meniscus tissue.

OBJECTIVE: To investigate the feasibility of synchrotron radiation-based phase contrast enhanced micro-computed tomography (SR-PhC-µCT) for imaging of human meniscus. Quantitative parameters related to fiber orientation and crimping were evaluated as potential markers of tissue degeneration. DESIGN: Human meniscus specimens from 10 deceased donors were prepared using different preparation schemes: fresh frozen and thawed before imaging or fixed and paraffin-embedded. The samples were imaged using SR-PhC-µCT with an isotropic voxel size of 1.625 µm. Image quality was evaluated by visual inspection and spatial resolution. Fiber voxels were defined using a grey level threshold and a structure tensor analysis was applied to estimate collagen fiber orientation. The area at half maximum (FAHM) was calculated from angle histograms to quantify orientation distribution. Crimping period was calculated from the power spectrum of image profiles of crimped fibers. Parameters were compared to degenerative stage as evaluated by Pauli histopathological scoring. RESULTS: Image quality was similar between frozen and embedded samples and spatial resolutions ranged from 5.1 to 5.8 µm. Fiber structure, including crimping, was clearly visible in the images. Fibers appeared to be less organized closer to the tip of the meniscus. Fiber density might decrease slightly with degeneration. FAHM and crimping period did not show any clear association with histopathological scoring. CONCLUSION: SR-PhC-µCT is a feasible technique for high-resolution 3D imaging of fresh frozen meniscus tissue. Further work is needed to establish quantitative parameters that relate to tissue degeneration, but this imaging technique is promising for future studies of meniscus structure and biomechanical response.

Cdk9 and H2Bub1 signal to Clr6-CII/Rpd3S to suppress aberrant antisense transcription.

Mono-ubiquitylation of histone H2B (H2Bub1) and phosphorylation of elongation factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (RNAPII), and are mutually dependent in fission yeast. It remained unclear whether Cdk9 and H2Bub1 cooperate to regulate the expression of individual genes. Here, we show that Cdk9 inhibition or H2Bub1 loss induces intragenic antisense transcription of ∼10% of fission yeast genes, with each perturbation affecting largely distinct subsets; ablation of both pathways de-represses antisense transcription of over half the genome. H2Bub1 and phospho-Spt5 have similar genome-wide distributions; both modifications are enriched, and directly proportional to each other, in coding regions, and decrease abruptly around the cleavage and polyadenylation signal (CPS). Cdk9-dependence of antisense suppression at specific genes correlates with high H2Bub1 occupancy, and with promoter-proximal RNAPII pausing. Genetic interactions link Cdk9, H2Bub1 and the histone deacetylase Clr6-CII, while combined Cdk9 inhibition and H2Bub1 loss impair Clr6-CII recruitment to chromatin and lead to decreased occupancy and increased acetylation of histones within gene coding regions. These results uncover novel interactions between co-transcriptional histone modification pathways, which link regulation of RNAPII transcription elongation to suppression of aberrant initiation.

Chronic pain after open inguinal hernia repair: expertise-based randomized clinical trial of heavyweight or lightweight mesh.

BACKGROUND: There is a shortage of high-quality studies regarding choice of mesh in open anterior inguinal hernia repair in relation to long-term chronic pain. The authors hypothesized that heavyweight compared with lightweight mesh causes increased postoperative pain. METHODS: An RCT was undertaken between 2007 and 2009 at two sites in Sweden. Men aged 25 years or older with an inguinal hernia evaluated in the outpatient clinic were randomized in an unblinded fashion to heavyweight or lightweight mesh for open anterior inguinal hernia repair. Data on pain affecting daily activities, as measured by the Short-Form Inguinal Pain Questionnaire 9-12 years after surgery, were collected as the primary outcome. Differences between groups were evaluated by generalized odds and numbers needed to treat. RESULTS: A total of 412 patients were randomized; 363 were analysed with 320 questionnaires sent out. A total of 271 questionnaires (84.7 per cent) were returned; of these, 121 and 150 patients were in the heavyweight and lightweight mesh groups respectively. Pain affecting daily activities was more pronounced in patients randomized to heavyweight versus lightweight mesh (generalized odds 1.33, 95 per cent c.i. 1.10 to 1.61). This translated into a number needed to treat of 7.06 (95 per cent c.i. 4.28 to 21.44). Two reoperations for recurrence were noted in the heavyweight mesh group, and one in the lightweight mesh group. CONCLUSION: A large-pore lightweight mesh causes significantly less pain affecting daily activities a decade after open anterior inguinal hernia repair. Registration number: NCT00451893 (http://www.clinicaltrials.gov).

Subclinical hyperthyroidism is associated with increased risk of vertebral fractures in older men.

In elderly men included in MrOS-Sweden, subclinical hyperthyroidism (SHyper) was markedly associated with increased risk of vertebral fractures. INTRODUCTION: Overt hyperthyroidism is associated with increased risk of fractures. However, only a few studies have investigated whether SHyper is associated with fracture risk in elderly men. We therefore investigated if SHyper was a risk factor for fractures in Swedish men. METHODS: We followed (median 9.8 years) elderly men (n = 1856; mean age 75, range 69-81 years) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. SHyper was defined as serum thyroid-stimulating hormone (TSH) < 0.45 mIU/L (n = 38). RESULTS: SHyper was associated with increased risk of all fractures [n = 456; hazard ratio (HR) adjusted for age, study center, and levothyroxine treatment = 1.99, 95% confidence interval (CI): 1.20-3.32], major osteoporotic fractures (MOF, n = 338; HR 2.44, 95% CI: 1.42-4.21), and vertebral fractures (n = 176; HR 3.79, 95% CI: 2.02-7.11). These associations remained after full adjustment for covariates including total hip bone mineral density and in subanalyses including only men with serum free thyroxine ≤ the upper normal limit. However, after exclusion of men receiving levothyroxine treatment, the associations with all fractures and MOF lost significance. CONCLUSIONS: In elderly Swedish men, there was a strong association between SHyper and increased risk of vertebral fractures, whereas the associations with all incident fractures and MOF need to be confirmed in further studies.

Association between glycaemic outcome and BMI in Danish children with type 1 diabetes in 2000-2018: a nationwide population-based study.

AIM: To describe the development of HbA1c and BMI over time in Danish children with type 1 diabetes; and to investigate the association between HbA1c and BMI including influence of age, gender, diabetes duration, severe hypoglycaemia and treatment method. METHODS: We used the nationwide Danish Registry of Childhood and Adolescent Diabetes, DanDiabKids, including annual registrations of all children with diabetes treated at Danish hospitals. With linear mixed-effects models and splines we analyzed the HbA1c and BMI development over time as well as the association between HbA1c and BMI including effects of gender, age, disease duration, hypoglycaemia and treatment method. BMI z-scores were calculated for these analyses. RESULTS: For the period from 2000 to 2018, 6097 children with type 1 diabetes were identified from the DanDiabKids database. The median (interquartile range) HbA1c level was 65 (57-74) mmol/mol (8.1%) and the median BMI z-score was 0.85 in girls and 0.67 in boys. A non-linear association was found between HbA1c and BMI z-score, with the highest BMI z-score observed for HbA1c values in the range of approximately 60-70 mmol/mol (7.6-6.8%). The association was modified by gender, age and diabetes duration. Severe hypoglycaemia and insulin pump treatment had a small positive impact on BMI z-score. CONCLUSION: The association between HbA1c and BMI z-score was non-linear, with the highest BMI z-score being observed for intermediate HbA1c levels; however, specific patterns depended on gender, age and diabetes duration.

Regulation of bile acid metabolism in biliary atresia: reduction of FGF19 by Kasai portoenterostomy and possible relation to early outcome.

BACKGROUND: Fibroblast growth factor 19 (FGF19) is produced in the small intestine and is involved in suppression of hepatic bile acid (BA) synthesis. FGF19 is also expressed in the liver and serum levels are elevated in adults with cholestatic liver disease. This may reflect a rescue mechanism to dampen liver injury caused by increased intrahepatic BAs. OBJECTIVES: To examine circulating FGF19 at early stages of biliary atresia and at short-term follow-up post-Kasai portoenterostomy (KPE) in relation to noncholestatic infants. The relationship between FGF19, BAs and markers for BA synthesis and hepatic gene expression of factors involved in BA metabolism were also evaluated. METHODS: Liver tissue, portal and peripheral blood samples were obtained from fifteen patients at KPE; additional blood was collected 4-6 months after surgery. Two control groups were included; to examine possible changes related to surgery and to compare FGF19 in biliary atresia to noncholestatic infants. RESULTS: Circulating FGF19 levels correlated to its hepatic gene expression at time of KPE in biliary atresia and levels were elevated compared to noncholestatic infants. At follow-up, FGF19 levels were markedly reduced, and the decline coincided with reductions in bilirubin and conjugated chenodeoxycholic acid and with increased levels of the BA synthesis marker C4. CONCLUSION: Elevated circulating FGF19 in biliary atresia is of hepatic origin and reduced following KPE. Changes in serum FGF19 may reflect the level of restoration of the enterohepatic circulation, and this warrants further long-term studies on the role of FGF19 in the cholestatic liver.

Hierarchical modularity and the evolution of genetic interactomes across species.

To date, cross-species comparisons of genetic interactomes have been restricted to small or functionally related gene sets, limiting our ability to infer evolutionary trends. To facilitate a more comprehensive analysis, we constructed a genome-scale epistasis map (E-MAP) for the fission yeast Schizosaccharomyces pombe, providing phenotypic signatures for ~60% of the nonessential genome. Using these signatures, we generated a catalog of 297 functional modules, and we assigned function to 144 previously uncharacterized genes, including mRNA splicing and DNA damage checkpoint factors. Comparison with an integrated genetic interactome from the budding yeast Saccharomyces cerevisiae revealed a hierarchical model for the evolution of genetic interactions, with conservation highest within protein complexes, lower within biological processes, and lowest between distinct biological processes. Despite the large evolutionary distance and extensive rewiring of individual interactions, both networks retain conserved features and display similar levels of functional crosstalk between biological processes, suggesting general design principles of genetic interactomes.

Interplay of water and reactive elements in oxidation of alumina-forming alloys.

High-temperature alloys are crucial to many important technologies that underpin our civilization. All these materials rely on forming an external oxide layer (scale) for corrosion protection. Despite decades of research on oxide scale growth, many open questions remain, including the crucial role of the so-called reactive elements and water. Here, we reveal the hitherto unknown interplay between reactive elements and water during alumina scale growth, causing a metastable 'messy' nano-structured alumina layer to form. We propose that reactive-element-decorated, hydroxylated interfaces between alumina nanograins enable water to access an inner cathode in the bottom of the scale, at odds with the established scale growth scenario. As evidence, hydride-nanodomains and reactive element/hydrogen (deuterium) co-variation are observed in the alumina scale. The defect-rich alumina subsequently recrystallizes to form a protective scale. First-principles modelling is also performed to validate the RE effect. Our findings open up promising avenues in oxidation research and suggest ways to improve alloy properties.

Osteoarthritis development related to cartilage quality-the prognostic value of dGEMRIC after anterior cruciate ligament injury.

OBJECTIVE: Rupture of the anterior cruciate ligament (ACL) increases the risk of developing osteoarthritis (OA). Delayed Gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) investigates cartilage integrity through T1-analysis after intravenous contrast injection. A high dGEMRIC index represents good cartilage quality. The main purpose of this prospective cohort study was to investigate the prognostic value of the dGEMRIC index regarding future knee OA. METHOD: 31 patients with ACL injury (mean age 27 ± 6.7 (±SD) years, 19 males) were examined after 2 years with 1.5T dGEMRIC of femoral cartilage. Re-examination 14 years post-injury included weight-bearing knee radiographs, Lysholm and Knee Osteoarthritis Outcome Score (KOOS). RESULTS: At the 14-year follow up radiographic OA (ROA) was present in 68% and OA symptoms (SOA) in 42% of the injured knees. The dGEMRIC index of the medial compartment was lower in knees that developed medial ROA, 325 ± 68 (ms±SD) vs 376 ± 47 (51 (7-94)) (difference of means (95% confidence interval (CI))), in patients that developed symptomatic OA (SOA), 327 ± 61 vs 399 ± 42 (52 (11-93)), and poor knee function 337 ± 54 vs 381 ± 52 (48 (7-89)) compared to those that did not develop ROA, SOA or poor function. The dGEMRIC index correlated negatively with the OARSI osteophyte score in medial (r = -0.44, P = 0.01) and lateral (r = -0.38, P = 0.03) compartments. CONCLUSION: The associations between a low dGEMRIC index and future ROA, as well as SOA, are in agreement with previous studies and indicate that dGEMRIC has a prognostic value for future knee OA.

Ultra-high field magnetic resonance imaging parameter mapping in the posterior horn of ex vivo human menisci.

OBJECTIVE: To investigate the relationship between meniscus magnetic resonance (MR) relaxation parameters and meniscus degradation through quantitative imaging of ex vivo posterior horns of menisci from subjects with and without knee osteoarthritis (OA). DESIGN: We sampled medial and lateral menisci from ten medial compartment knee OA patients (mean age 63 years) undergoing total knee replacement and from ten deceased donors (references, mean age 51 years). MR relaxation parameters T2*, T2 and T1 of the posterior horn were measured at a 9.4 T scanner. Comparisons were made between OA patients and references (with adjustment for age) as well as between medial and lateral menisci from the same knees. RESULTS: Mean values (standard deviation) of mean T2* were 13 (3.8), 6.9 (2.3), 7.2 (1.9) and 7.2 (1.7) ms for the medial and lateral patient menisci and the medial and lateral reference menisci, respectively. Corresponding values were 17 (3.7), 9.0 (2.2), 12 (4) and 9.0 (1.3) ms for T2 and 1810 (150), 1630 (30), 1580 (90) and 1560 (50) ms for T1. All three relaxation times were significantly longer in medial OA menisci compared to the other groups. Among medial reference menisci, relaxation times (mainly T1) tended to increase with age. CONCLUSIONS: MR relaxation times T2*, T2 and T1 in the posterior horn are longer in the medial menisci of patients with end-stage medial compartment knee OA compared to the corresponding lateral menisci and to reference menisci. The meniscus seems to undergo intrasubstance alterations related to both OA and ageing.

First Observation of a Stable Highly Dissipative Divertor Plasma Regime on the Wendelstein 7-X Stellarator.

For the first time, the optimized stellarator Wendelstein 7-X has operated with an island divertor. An operation regime in hydrogen was found in which the total plasma radiation approached the absorbed heating power without noticeable loss of stored energy. The divertor thermography recorded simultaneously a strong reduction of the heat load on all divertor targets, indicating almost complete power detachment. This operation regime was stably sustained over several energy confinement times until the preprogrammed end of the discharge. The plasma radiation is mainly due to oxygen and is located at the plasma edge. This plasma scenario is reproducible and robust at various heating powers, plasma densities, and gas fueling locations. These experimental results show that the island divertor concept actually works and displays good power dissipation potential, producing a promising exhaust concept for the stellarator reactor line.

A nationwide study on the incidence of mesenteric ischaemia after surgery for rectal cancer demonstrates an association with high arterial ligation.

AIM: The incidence of mesenteric ischaemia after resection for rectal cancer has not been investigated in a population-based setting. The use of high ligation of the inferior mesenteric artery might cause such ischaemia, as the bowel left in situ depends on collateral blood supply after a high tie. METHOD: The Swedish Colorectal Cancer Registry was used to identify all patients subjected to an abdominal resection for rectal cancer during the years 2007-2017 inclusive. Mesenteric ischaemia within the first 30 postoperative days was recorded, classified as either stoma necrosis or colonic necrosis. Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for mesenteric ischaemia in relation to high tie, with adjustment for confounding. RESULTS: Some 14 657 patients were included, of whom 59 (0.40%) had a reoperation for any type of mesenteric ischaemia, divided into 34 and 25 cases of stoma necrosis and colonic necrosis, respectively. Compared with patients who did not require reoperation for mesenteric ischaemia following rectal cancer surgery, the proportion having high tie was greater (54.2% vs 38.5%; P = 0.032). The adjusted OR for reoperation due to any mesenteric ischaemia with high tie was 2.26 (95% CI 1.34-3.79), while the corresponding estimates for stoma and colonic necrosis, respectively, were 1.60 (95% CI 0.81-3.17) and 3.69 (95% CI 1.57-8.66). CONCLUSION: The incidence of reoperation for mesenteric ischaemia after abdominal resection for rectal cancer is low, but the use of a high tie might increase the risk of colonic necrosis demanding surgery.

A nucleosome turnover map reveals that the stability of histone H4 Lys20 methylation depends on histone recycling in transcribed chromatin.

Nucleosome composition actively contributes to chromatin structure and accessibility. Cells have developed mechanisms to remove or recycle histones, generating a landscape of differentially aged nucleosomes. This study aimed to create a high-resolution, genome-wide map of nucleosome turnover in Schizosaccharomyces pombe. The recombination-induced tag exchange (RITE) method was used to study replication-independent nucleosome turnover through the appearance of new histone H3 and the disappearance or preservation of old histone H3. The genome-wide location of histones was determined by chromatin immunoprecipitation-exonuclease methodology (ChIP-exo). The findings were compared with diverse chromatin marks, including histone variant H2A.Z, post-translational histone modifications, and Pol II binding. Finally, genome-wide mapping of the methylation states of H4K20 was performed to determine the relationship between methylation (mono, di, and tri) of this residue and nucleosome turnover. Our analysis showed that histone recycling resulted in low nucleosome turnover in the coding regions of active genes, stably expressed at intermediate levels. High levels of transcription resulted in the incorporation of new histones primarily at the end of transcribed units. H4K20 was methylated in low-turnover nucleosomes in euchromatic regions, notably in the coding regions of long genes that were expressed at low levels. This transcription-dependent accumulation of histone methylation was dependent on the histone chaperone complex FACT. Our data showed that nucleosome turnover is highly dynamic in the genome and that several mechanisms are at play to either maintain or suppress stability. In particular, we found that FACT-associated transcription conserves histones by recycling them and is required for progressive H4K20 methylation.

Persisting CAM deformity is associated with early cartilage degeneration after Slipped Capital Femoral Epiphysis: 11-year follow-up including dGEMRIC.

OBJECTIVE: Slipped capital femoral epiphysis (SCFE) in adolescence is associated with increased risk of future osteoarthritis (OA). The purpose of this study was to study clinical and radiographic risk factors for early cartilage degeneration after SCFE. DESIGN: 22 patients (44 hips) (mean age 24 years, range 18-27) treated with in situ fixation (The Hansson hook-pin) for stable SCFE on average 11 years previously were investigated. Cartilage status was assessed with delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). The alpha angle, reflecting femoroacetabular impingement (FAI), and the original slip angle were measured. Clinical outcome was assessed with the Copenhagen hip and groin outcome score (HAGOS) and clinical examination. RESULTS: The dGEMRIC index was lower in SCFE hips than unaffected hips 456 ms (CI 419-493) vs 521 ms (CI 476-567) (P = 0.03). The difference was larger (mean 21 ms) in anterior than posterior regions of the hip (P = 0.038). The alpha angle was higher in SCFE hips, 61.5° (CI 53.9-69.1) vs 45.6° (CI 43.6-47.6), (P < 0.001). The alpha angle, but not the original slip angle, correlated negatively with the dGEMRIC index (R = -0.40, P = 0.046). There was a positive correlation between HAGOS and the dGEMRIC-index (R = 0.41, P = 0.012). CONCLUSIONS: Early cartilage degeneration after SCFE seems related to persisting FAI in adulthood, rather than the initial slip severity. The correlation between dGEMRIC and HAGOS indicates a clinical relevance of the MRI findings. Our results suggest that FAI after SCFE should be evaluated already after physeal closure in order to predict and possibly prevent future OA development.

Optimization of soft X-ray phase-contrast tomography using a laser wakefield accelerator.

X-ray phase-contrast imaging allows for non-invasive analysis in low-absorbing materials, such as soft tissue. Its application in medical or materials science has yet to be realized on a wider scale due to the requirements on the X-ray source, demanding high flux and small source size. Laser wakefield accelerators generate betatron X-rays fulfilling these criteria and can be suitable sources for phase-contrast imaging. In this work, we present the first phase-contrast images obtained by using ionization injection-based laser wakefield acceleration, which results in a higher photon yield and smoother X-ray beam profile compared to self-injection. A peak photon yield of 1.9 × 1011 ph/sr and a source size of 3 µm were estimated. Furthermore, the current laser parameters produce an X-ray spectrum mainly in the soft X-ray range, in which laser-plasma based phase-contrast imaging had yet to be studied. The phase-contrast images of a Chrysopa lacewing resolve features on the order of 4 µm. These images are further used for a tomographic reconstruction and a volume rendering, showing details on the order of tens of µm.