Cascades of Parametric Instabilities in the Tokamak Plasma Edge during Electron Cyclotron Resonance Heating.

We report observations of nonlinear two-plasmon decay instabilities (TPDIs) of a high-power microwave beam, a process similar to half-harmonic generation in optics, during electron cyclotron resonance heating in a tokamak. TPDIs are found to occur regularly in the plasma edge due to wave trapping in density fluctuations for various confinement modes, and the frequencies of both observed daughter waves agree with modeling. Emissions from a cascade of subsequent decays, which indicate a generation of ion Bernstein waves, are correlated with fast-ion generation. This emphasizes the limitations of standard linear microwave propagation models and possibly paves the way for novel microwave applications in plasmas.

"What matters to you" on the day of surgery: Protocol for a mixed methods study.

BACKGROUND: The anticipation of anesthesia and surgery is the source of fear and anxiety in millions of patients worldwide. Although patients' fear and anxiety are recognized, more knowledge is needed to address patient responses and needs. Understanding the needs of the patients are important, and asking patients directly is the first step towards addressing these needs. This again might help reducing medications such as anesthetics and postoperative pain relief. The aim of this study protocol is to describe how we will investigate what matters to patients on the day of surgery, as well as their degree-of-worry and surgical fear. METHODS: Using a convergent mixed methods design with equal weighting of the qualitative and quantitative data strand we take advantage of the international "What Matters To You" Day on June 6, 2024 to conduct a flash mob study. We will approach perioperative departments around Denmark to participate and eligible patients arriving to the perioperative department for surgery will be invited to participate. Consenting patients are asked to complete a survey in three parts regarding (1) what matters to you, (2) degree-of-worry, and (3) surgical fear. We will use qualitative analysis for the first part and descriptive statistics for second and third parts. The data strands will be analyzed separately followed by integrated analysis and joint displays.

Disparities in alcohol- and substance-related hospitalizations and deaths across sexual orientations in Canada: a longitudinal study.

OBJECTIVES: We aim to quantify disparities in substance-related acute events (i.e. hospitalizations and deaths for substances, including alcohol, cannabis, opioids, narcotics, and/or illicit drugs) across sexual orientations based on health administrative data. STUDY DESIGN: This was a longitudinal analysis from six waves of the Canadian Community Health Survey (2009-2014) linked to hospitalization/mortality data in Ontario, Canada. METHODS: The study sample consisted of survey respondents aged ≥15 (weighted n = 15,406,000) who provided a valid response to the question about sexual orientation. The primary outcome was substance-related acute events, including hospitalizations and deaths due to alcohol, cannabis, opioids, narcotics, and/or illicit drugs. Disparities in substance-related acute events across sexual orientation and gender were examined using flexible parametric survival analysis. RESULTS: Bisexual women had hazard ratios of 2.46 (95% confidence interval: 1.46-4.15) for any substance-related acute event and 2.67 (95% confidence interval: 1.42-5.00) for non-alcohol substance acute events compared to heterosexual women. Lesbian women did not exhibit significant differences in acute event risk compared to heterosexual women. Gay and bisexual men demonstrated elevated but not statistically significant risks compared to heterosexual men. CONCLUSIONS: Bisexual women face higher risks of substance-related acute events, potentially due to self-medication of unique stressors brought on by discrimination and isolation. Enhanced education and training for healthcare professionals are essential to increase awareness and sensitivity toward the heightened substance use risk among lesbian, gay, and bisexual individuals. Targeted interventions aimed at reducing substance use problems among bisexual individuals warrant increased funding and research.

Second Data Release from the European Pulsar Timing Array: Challenging the Ultralight Dark Matter Paradigm.

Pulsar Timing Array experiments probe the presence of possible scalar or pseudoscalar ultralight dark matter particles through decade-long timing of an ensemble of galactic millisecond radio pulsars. With the second data release of the European Pulsar Timing Array, we focus on the most robust scenario, in which dark matter interacts only gravitationally with ordinary baryonic matter. Our results show that ultralight particles with masses 10^{-24.0} eV≲m≲10^{-23.3} eV cannot constitute 100% of the measured local dark matter density, but can have at most local density ρ≲0.3 GeV/cm^{3}.

Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial.

OBJECTIVES: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. METHOD: One-hundred patients with established RA, Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. RESULTS: Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0-2.6), HAQ score (0.08, 0.03-0.1), MRI combined inflammation (2.5, 0.9-4.1), and SDAI scores (2.7, 1.9-3.5). CONCLUSIONS: Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01656278.

Type of hormonal treatment administered to induce vitellogenesis in European eel influences biochemical composition of eggs and yolk-sac larvae.

Egg biochemical composition is among the main factors affecting offspring quality and survival during the yolk-sac stage, when larvae depend exclusively on yolk nutrients. These nutrients are primarily embedded in the developing oocytes during vitellogenesis. In aquaculture, assisted reproduction procedures may be applied enabling gamete production. For the European eel (Anguilla anguilla), reproductive treatment involves administration of pituitary extracts from carp (CPE) or salmon (SPE) to induce and sustain vitellogenesis. In the present study, we compared the influence of CPE and SPE treatments on offspring quality and composition as well as nutrient utilization during the yolk-sac stage. Thus, dry weight, proximal composition (total lipid, total protein), free amino acids, and fatty acids were assessed in eggs and larvae throughout the yolk-sac stage, where body and oil-droplet area were measured to estimate growth rate, oil-droplet utilization, and oil-droplet utilization efficiency. The results showed that CPE females spawned eggs with higher lipid and free amino acid contents. However, SPE females produced more buoyant eggs with higher fertilization rate as well as larger larvae with more energy reserves (estimated as oil-droplet area). Overall, general patterns of nutrient utilization were detected, such as the amount of total lipid and monounsaturated fatty acids decreasing from the egg stage and throughout the yolk-sac larval stage. On the contrary, essential fatty acids and free amino acids were retained. Notably, towards the end of the yolk-sac stage, the proximal composition and biometry of surviving larvae, from both treatments, were similar.

The patient enablement instrument for back pain: reliability, content validity, construct validity and responsiveness.

BACKGROUND: Currently, there are no outcome measures assessing the ability of people with non-specific low back pain to self-manage their illness. Inspired by the 'Patient Enablement Instrument', we developed the Patient Enablement Instrument for Back Pain (PEI-BP). The aim of this study was to describe the development of the Patient Enablement Instrument for Back Pain (PEI-BP) and investigate content validity, construct validity, internal consistency, test-retest reliability, measurement error, responsiveness and floor and ceiling effects. METHODS: The PEI-BP consists of 6 items that are rated on a 0-10 Numeric Rating Scale. Measurement properties were evaluated using the COSMIN taxonomy and were based on three cohorts from primary care with low back pain: The content validity cohort (N = 14) which participated in semi-structured interviews, the GLA:D® Back cohort (N = 272) and the test-retest cohort (N = 37) which both completed self-reported questionnaires. For construct validity and responsiveness, enablement was compared to disability (Oswestry Disability Index), back pain beliefs (Brief Illness Perception Questionnaire), fear avoidance (Fear-Avoidance Beliefs Questionnaire-physical activity), mental health (SF-36), educational level and number of previous episodes of low back pain. RESULTS: The PEI-BP was found to have acceptable content validity, construct validity, reliability (internal consistency, test-retest reliability and measurement error) and responsiveness. The Smallest Detectable Change was 10.1 points illustrating that a patient would have to change more than 1/6 of the scale range for it to be a true change. A skewed distribution towards the high scores were found at baseline indicating a potentially problematic ceiling effect in the current population. CONCLUSIONS: The PEI-BP can be considered a valid and reliable tool to measure enablement on people seeking care for non-specific LBP. Further testing of the PEI-BP in populations with more severe LBP is recommended. TRIAL REGISTRATION: Not applicable.

A comparative analysis of heterogeneity in commercially available recombinant factor VIII products.

INTRODUCTION: Advances in analytical technologies enable investigation of possible correlations between molecular structure, aggregation and subvisible particle content. Regulatory agencies place increasing attention on potential risks associated with protein aggregates in the micron range in biological therapeutics. AIM: Assess the heterogeneity, high-molecular-weight protein (HMWP) species, subvisible particle content and posttranslational modifications in six commercially available recombinant FVIII (rFVIII) products. METHODS: Three B-domain-deleted (BDD) or B-domain truncated rFVIII products (turoctocog alfa, simoctocog alfa and moroctocog alfa) and three full-length rFVIII products (octocog alfa FS and two octocog alfa) were analysed. HMWP content, amount of micron range subvisible particles, tyrosine-1680 sulphation and N-glycan analysis were investigated. RESULTS: The B-domain-modified products had more protein size homogeneity vs the full-length products. Size exclusion-high-performance liquid chromatography data indicated no association between B-domain structure and aggregate content or size of the products tested. The rFVIII products showed large variation in subvisible particle concentration, with turoctocog alfa and simoctocog alfa having the lowest numbers (1000-1600 and 1800-2400 particles/100 IU, respectively). Turoctocog alfa and simoctocog alfa displayed the most complete tyrosine sulphation (>99.5%). CONCLUSION: Overall, there was no association between molecular structure (full-length B-domain, BDD or truncated) and subvisible particle or HMWP content. Dissimilarities may be related to production and product handling differences. In this study, turoctocog alfa, such as simoctocog alfa, had one of the lowest levels of subvisible particles and HMWP content, and high protein size homogeneity.

Composition in the Interface between Clay Mineral Surfaces and Divalent Cation Electrolytes.

The interfacial free energy of a solid, which determines its adsorption properties, depends on interactions between the surface and the fluid. A change in surface composition can completely change the behavior of the solid. Decades of work have explored adsorption and its effects at solid-fluid interfaces from the macroscopic perspective and using molecular modeling, so the concept of the electric double layer (EDL) is well established in the community. However, direct, molecular level, experimental observations of the composition within the interface region, and its change with time and conditions, are not abundant. We used cryogenic X-ray photoelectron spectroscopy (cryoXPS) to observe the composition in the clay mineral-solution interface region as a function of bulk solution composition, on illite and chlorite in MgCl2 and CaCl2 electrolytes, over a range of concentrations (1-125 mM), in situ, on vitrified samples. These samples were prepared from very thin smears of centrifuged wet paste that were instantaneously chilled to liquid N2 temperature. They preserved the adsorbed solution in its amorphous state, maintaining the location of the ions and water with respect to the solid, without the disruption that occurs during drying or the rearrangement that results as water crystallizes during freezing. With decreasing ionic strength, we could directly monitor the loss of negative charge in the interface region, producing an anion deficiency, as predicted by theory. The Cl-/Me2+ ratio dropped below 1 for chlorite at 12-25 mM MeCl2 and for illite at 75-100 mM. In addition to better understanding of clay mineral behavior in solution, this work demonstrates that only those clay minerals where surface charge density is the same or lower than that for chlorite contribute to a low salinity enhanced oil recovery response (LS EOR). This explains many of the contradictory results from studies about the role of clay minerals in LS EOR.

Local bone loss in patients with anti-citrullinated peptide antibody and arthralgia, evaluated with high-resolution peripheral quantitative computed tomography.

OBJECTIVE: To investigate bone changes in the metacarpophalangeal (MCP) joints of anti-citrullinated peptide antibody (ACPA)-positive patients with arthralgia, but not arthritis, compared to healthy controls. METHOD: Using a cross-sectional study design, patients were recruited from hospitals and private care rheumatologists, and controls from a test subject website. All subjects underwent medical history interview, clinical examination, and biochemical screening including ACPA. Patients with positive ACPA, arthralgia, and no rheumatic disease were included. Controls without a history or signs of rheumatological disease or positive ACPA were included. A 2.7-cm-long region around the second and third MCP joints was evaluated using high-resolution peripheral quantitative computed tomography with a voxel size of 82 µm. RESULTS: Twenty-nine ACPA-positive patients and 29 healthy controls were evaluated. Trabecular volumetric bone mineral density and bone volume fraction did not differ between the groups. In addition, the cortical bone was not affected in patients, as we found no difference in average cortical thickness and cortical bone area between the groups. In contrast, the trabeculae were significantly (p < 0.05) thinner in both second and third MCP heads compared with controls, whereas trabecular number and trabecular separation did not differ between the groups. No erosions were demonstrated and the number of non-specific breaks did not differ between the groups. CONCLUSION: Trabecular bone changes were observed in ACPA-positive patients with arthralgia compared with healthy controls. The results may reflect inflammatory up-regulated trabecular bone resorption leading to early bone loss before the onset of clinical arthritis.

Long-term epidemiological dynamics of dengue in Barbados - one of the English-speaking Caribbean countries.

Using the dengue surveillance program, we prospectively collected data on all the suspected and confirmed cases of dengue in Barbados from 2006 to 2015. Data were analysed for demographic, seasonal and temporal dynamics of this disease in this country. The overall mean annual incidence rate of suspected and confirmed dengue over the study period was 0.49% (range 0.15%-0.99%) and 0.16% (range 0.05%-0.48%), respectively. There was a significant correlation between the mean monthly number of confirmed cases, the mean monthly rainfall and the mean monthly relative humidity percentage. Dengue in this population is predominantly an infection affecting children and young adults. The median age of the patients with both, suspected and confirmed dengue was 25 years and the highest proportion of cases was seen in the age group 0-15 years. The annual incidence rates of both the suspected and the confirmed cases showed an upward trend during the study period and this upward trend was more pronounced among children.

Chronic maternal inflammation or high-fat-feeding programs offspring obesity in a sex-dependent manner.

BACKGROUND/OBJECTIVES: The current world-wide obesity epidemic partially results from a vicious circle whereby maternal obesity during pregnancy predisposes the offspring for accelerated weight gain and development of metabolic syndrome. Here we investigate whether low-grade inflammation, characteristic of the obese state, provides a causal role for this disastrous fetal programming in mice. METHODS: We exposed pregnant and lactating C57BL/6JBom female mice to either high-fat diet (HFD), or continuous infusion of lipopolysaccharide (LPS), a potent trigger of innate immunity, and studied offspring phenotypes. RESULTS: Both maternal LPS or HFD treatments rendered the offspring hyperphagic and inept of coping with a HFD challenge during adulthood, increasing their adiposity and weight gain. The metabolic effects were more pronounced in female offspring, while exposed male offspring mounted a larger inflammatory response to HFD at adulthood. CONCLUSIONS: This supports our hypothesis and highlights the programming potential of inflammation in obese pregnancies.

Left ventricular function at two-year follow-up in treatment-naive rheumatoid arthritis patients is associated with anti-cyclic citrullinated peptide antibody status: a cohort study.

OBJECTIVES: In rheumatoid arthritis (RA), the role of autoimmunity, especially anti-cyclic citrullinated peptide antibody (anti-CCP) level, and the time-course of left ventricular (LV) function is unknown. The objective was to assess LV function and the amount of coronary calcium in relation to anti-CCP levels in a cohort of treatment-naive RA patients, and to assess changes in these parameters during a 2 year follow-up period. METHOD: Sixty-six steroid- and disease-modifying anti-rheumatic drug-naive RA patients were treated with methotrexate according to the Danish national guidelines. We assessed LV function by conventional echocardiography and speckle-tracking echocardiography. We estimated the amount and progression of coronary calcium by coronary computed tomography. Patients were examined at the time of diagnosis and after 2 years. RESULTS: Patients with elevated anti-CCP at baseline and after 2 years, compared to those with non-persistently elevated anti-CCP, had significantly less improvement in S´ (1 ± 1.4 cm/s vs 0.2 ± 0.9 cm/s; p = 0.04) and a worsening in global longitudinal systolic strain (GLS) (0.6 ± 1.8% vs -1 ± 2.8%; p = 0.04). There was a significant correlation between ΔGLS over 2 years and anti-CCP at 2 year follow-up (r = 0.36; p = 0.006). We observed a small progression of coronary calcium score during the 2 year follow-up period. No differences in progression were found between patients with high anti-CCP titres at baseline and 2 year follow-up (n = 12) and patients with normal/low anti-CCP titres (n = 32) (23.8 ± 40.3 vs 22.6 ± 68.9; p = 0.96). CONCLUSIONS: Deformation analysis by speckle-tracking echocardiography is a valuable tool to detect early development of myocardial dysfunction despite normal ejection fraction in RA.

Return of spontaneous circulation and long-term survival according to feedback provided by automated external defibrillators.

BACKGROUND: We aimed to investigate the effect of automated external defibrillator (AED) feedback mechanisms on survival in out-of-hospital cardiac arrest (OHCA) victims. In addition, we investigated converting rates in patients with shockable rhythms according to AED shock waveforms and energy levels. METHODS: We collected data on OHCA occurring between 2011 and 2014 in the Capital Region of Denmark where an AED was applied prior to ambulance arrival. Patient data were obtained from the Danish Cardiac Arrest Registry and medical records. AED data were retrieved from the Emergency Medical Dispatch Centre (EMDC) and information on feedback mechanisms, energy waveform and energy level was downloaded from the applied AEDs. RESULTS: A total of 196 OHCAs had an AED applied prior to ambulance arrival; 62 of these (32%) provided audio visual (AV) feedback while no feedback was provided in 134 (68%). We found no difference in return of spontaneous circulation (ROSC) at hospital arrival according to AV-feedback; 34 (55%, 95% confidence interval (CI) [13-67]) vs. 72 (54%, 95% CI [45-62]), P = 1 (odds ratio (OR) 1.1, 95% CI [0.6-1.9]) or 30-day survival; 24 (39%, 95% CI [28-51]) vs. 53 (40%, 95% CI [32-49]), P = 0.88 (OR 1.1 (95% CI [0.6-2.0])). Moreover, we found no difference in converting rates among patients with initial shockable rhythm receiving one or more shocks according to AED energy waveform and energy level. CONCLUSIONS: No difference in survival after OHCA according to AED feedback mechanisms, nor any difference in converting rates according to AED waveform or energy levels was detected.

Occupational rhinoconjunctivitis caused by the common indoor plant, Hoya compacta.

BACKGROUND: Allergic reactions to the common house plant Hoya compacta (HC) have not previously been described. AIMS: To confirm HC as the cause of rhinoconjunctivitis in three horticultural workers. METHODS: Greenhouse working conditions were reproduced in our challenge chamber. RESULTS: All three cases developed rhinoconjunctivitis when working with HC plants. A control challenge was performed in two cases with iceberg lettuce causing no symptoms. Nasal volume measured by acoustic rhinometry (AR) fell after all three active challenges, but also after one of the control challenges. CONCLUSIONS: Our study confirms that HC may cause occupational rhinoconjunctivitis and asthma through a Type I hypersensitivity reaction. Specific inhalation challenges, nasal nitric oxide measurement and AR may be useful additional tools in supporting such diagnoses for occupational physicians to consider.

Is the Relationship between Cortical and White Matter Pathologic Changes in Multiple Sclerosis Spatially Specific? A Multimodal 7-T and 3-T MR Imaging Study with Surface and Tract-based Analysis.

PURPOSE: To investigate in vivo the spatial specificity of the interdependence between intracortical and white matter (WM) pathologic changes as function of cortical depth and distance from the cortex in multiple sclerosis (MS), and their independent contribution to physical and cognitive disability. MATERIALS AND METHODS: This study was institutional review board-approved and participants gave written informed consent. In 34 MS patients and 17 age-matched control participants, 7-T quantitative T2* maps, 3-T T1-weighted anatomic images for cortical surface reconstruction, and 3-T diffusion tensor images (DTI) were obtained. Cortical quantitative T2* maps were sampled at 25%, 50%, 75% depth from pial surface. Tracts of interest were reconstructed by using probabilistic tractography. The relationship between DTI metrics voxelwise of the tracts and cortical integrity in the projection cortex was tested by using multilinear regression models. RESULTS: In MS, DTI abnormal findings along tracts correlated with quantitative T2* changes (suggestive of iron and myelin loss) at each depth of the cortical projection area (P < .01, corrected). This association, however, was not spatially specific because abnormal findings in WM tracts also related to cortical pathologic changes outside of the projection cortex of the tract (P < .001). Expanded Disability Status Scale pyramidal score was predicted by axial diffusivity along the corticospinal tract (ß = 4.6 × 10(3); P < .001), Symbol Digit Modalities Test score by radial diffusivity along the cingulum (ß = -4.3 × 10(4); P < .01), and T2* in the cingulum cortical projection at 25% depth (ß = -1.7; P < .05). CONCLUSION: Intracortical and WM injury are concomitant pathologic processes in MS, which are not uniquely distributed according to a tract-cortex-specific pattern; their association may reflect a common stage-dependent mechanism.

Low-to-High Confinement Transition Mediated by Turbulence Radial Wave Number Spectral Shift in a Fusion Plasma.

A new model for the low-to-high (L-H) confinement transition has been developed based on a new paradigm for turbulence suppression by velocity shear [G. M. Staebler et al., Phys. Rev. Lett. 110, 055003 (2013)]. The model indicates that the L-H transition can be mediated by a shift in the radial wave number spectrum of turbulence, as evidenced here, for the first time, by the direct observation of a turbulence radial wave number spectral shift and turbulence structure tilting prior to the L-H transition at tokamak edge by direct probing. This new mechanism does not require a pretransition overshoot in the turbulent Reynolds stress, shunting turbulence energy to zonal flows for turbulence suppression as demonstrated in the experiment.

Psychosocial therapy and causes of death after deliberate self-harm: a register-based, nationwide multicentre study using propensity score matching.

BACKGROUND: Psychosocial therapy after deliberate self-harm might be associated with reduced risk of specific causes of death. METHOD: In this matched cohort study, we included patients, who after an episode of deliberate self-harm received psychosocial therapy at a Suicide Prevention Clinic in Denmark between 1992 and 2010. We used propensity score matching in a 1:3 ratio to select a comparison group from 59 046 individuals who received standard care. National Danish registers supplied data on specific causes of death over a 20-year follow-up period. RESULTS: At the end of follow-up, 391 (6.9%) of 5678 patients in the psychosocial therapy group had died, compared with 1736 (10.2%) of 17 034 patients in the matched comparison group. Lower odds ratios of dying by mental or behavioural disorders [0.54, 95% confidence interval (CI) 0.37-0.79], alcohol-related causes (0.63, 95% CI 0.50-0.80) and other diseases and medical conditions (0.61, 95% CI 0.49-0.77) were noted in the psychosocial therapy group. Also, we found a reduced risk of dying by suicide as well as other external causes, however, not by neoplasms and circulatory system diseases. Numbers needed to treat were 212.9 (95% CI 139.5-448.4) for mental or behavioural disorders as a cause of death, 111.1 (95% CI 79.2-210.5) for alcohol-related causes and 96.8 (95% CI 69.1-161.8) for other diseases and medical conditions. CONCLUSIONS: Our findings indicate that psychosocial therapy after deliberate self-harm might reduce long-term risk of death from select medical conditions and external causes. These promising results should be tested in a randomized design.

A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging.

We used a surface-based analysis of T2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T2* throughout the cortical width, to map in vivo the spatial distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (≤ 3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (≥ 4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T2* maps were registered to anatomical cortical surfaces for sampling T2* at 25%, 50% and 75% depth from the pial surface. Differences in laminar quantitative T2* between each patient group and controls were assessed using general linear model (P < 0.05 corrected for multiple comparisons). In all 41 multiple sclerosis cases, we tested for associations between laminar quantitative T2*, neurological disability, Multiple Sclerosis Severity Score, cortical thickness, and white matter lesions. In patients, we measured, T2* in intracortical lesions and in the intracortical portion of leukocortical lesions visually detected on 7 T scans. Cortical lesional T2* was compared with patients' normal-appearing cortical grey matter T2* (paired t-test) and with mean cortical T2* in controls (linear regression using age as nuisance factor). Subjects with multiple sclerosis exhibited relative to controls, independent from cortical thickness, significantly increased T2*, consistent with cortical myelin and iron loss. In early disease, T2* changes were focal and mainly confined at 25% depth, and in cortical sulci. In later disease stages T2* changes involved deeper cortical laminae, multiple cortical areas and gyri. In patients, T2* in intracortical and leukocortical lesions was increased compared with normal-appearing cortical grey matter (P < 10(-10) and P < 10(-7)), and mean cortical T2* in controls (P < 10(-5) and P < 10(-6)). In secondary progressive multiple sclerosis, T2* in normal-appearing cortical grey matter was significantly increased relative to controls (P < 0.001). Laminar T2* changes may, thus, result from cortical pathology within and outside focal cortical lesions. Neurological disability and Multiple Sclerosis Severity Score correlated each with the degree of laminar quantitative T2* changes, independently from white matter lesions, the greatest association being at 25% depth, while they did not correlate with cortical thickness and volume. These findings demonstrate a gradient in the expression of cortical pathology throughout stages of multiple sclerosis, which was associated with worse disability and provides in vivo evidence for the existence of a cortical pathological process driven from the pial surface.