Ultrafast modulation of the chemical potential in BaFe2_2As2_2 by coherent phonons

Time- and angle-resolved extreme ultraviolet photoemission spectroscopy is used to study the electronic structure dynamics in BaFe$_2$As$_2$ around the high-symmetry points $\Gamma$ and $M$. A global oscillation of the Fermi level at the frequency of the $A_{1g}$(As) phonon mode is observed. It is argued that this behavior reflects a modulation of the effective chemical potential in the photoexcited surface region that arises from the high sensitivity of the band structure near the Fermi level to the $A_{1g}$ phonon mode combined with a low electron diffusivity perpendicular to the layers. The results establish a novel way to tune the electronic properties of iron pnictides: coherent control of the effective chemical potential. The results further suggest that the equilibration time for the effective chemical potential needs to be considered in the ultrafast electronic structure dynamics of materials with weak interlayer coupling.Comment: 6 pages, 3 figure

Ultrafast modulation of the chemical potential in BaFe2As2 by coherent phonons

Time- and angle-resolved extreme ultraviolet photoemission spectroscopy is used to study the electronic structure dynamics in BaFe2As2 around the high-symmetry points Γ and M. A global oscillation of the Fermi level at the frequency of the A1g(As) phonon mode is observed. It is argued that this behavior reflects a modulation of the effective chemical potential in the photoexcited surface region that arises from the high sensitivity of the band structure near the Fermi level to the A1g(As) phonon mode combined with a low electron diffusivity perpendicular to the layers. The results establish a novel way to tune the electronic properties of iron pnictides: coherent control of the effective chemical potential. The results further suggest that the equilibration time for the effective chemical potential needs to be considered in the ultrafast electronic structure dynamics of materials with weak interlayer coupling. © 2014 American Physical Society

On the survival of Floquet-Bloch states in the presence of scattering

Floquet theory has spawned many exciting possibilities for electronic structure control with light with enormous potential for future applications. The experimental realization in solids, however, largely remains pending. In particular, the influence of scattering on the formation of Floquet-Bloch states remains poorly understood. Here we combine time- and angle-resolved photoemission spectroscopy with time-dependent density functional theory and a two-level model with relaxation to investigate the survival of Floquet-Bloch states in the presence of scattering. We find that Floquet-Bloch states will be destroyed if scattering -- activated by electronic excitations -- prevents the Bloch electrons from following the driving field coherently. The two-level model also shows that Floquet-Bloch states reappear at high field intensities where energy exchange with the driving field dominates over energy dissipation to the bath. Our results clearly indicate the importance of long scattering times combined with strong driving fields for the successful realization of various Floquet phenomena.Comment: 27 pages, 5 figue

The Association Between the Development of Cam Morphology During Skeletal Growth in High-Impact Athletes and the Presence of Cartilage Loss and Labral Damage in Adulthood:A Prospective Cohort Study With a 12-Year Follow-up

Background: Cam morphology develops during skeletal growth, but its influence on cartilage and the labrum in high-impact athletes later in life is unknown. Purpose: To (1) explore the association between the presence and duration of cam morphology during adolescence and the cartilage and labral status 7 to 12 years later and (2) report the prevalence of cartilage loss and labral damage in a population of young male athletes (&lt;32 years old) who played professional soccer during skeletal growth. Study Design: Cohort study (Prognosis); Level of evidence, 2. Methods: A total of 89 healthy male academy soccer players from the Dutch soccer club Feyenoord (aged 12-19 years) were included at baseline. At baseline and 2.5- and 5-year follow-ups, standardized supine anteroposterior pelvis and frog-leg lateral radiographs of each hip were obtained. At 12-year follow-up, magnetic resonance imaging of both hips was performed. Cam morphology was defined by a validated alpha angle ≥60° on radiographs at baseline or 2.5- or 5-year follow-up when the growth plates were closed. Hips with the presence of cam morphology at baseline or at 2.5-year follow-up were classified as having a “longer duration” of cam morphology. Hips with cam morphology only present since 5-year follow-up were classified as having a “shorter duration” of cam morphology. At 12-year follow-up, cartilage loss and labral abnormalities were assessed semiquantitatively. Associations were estimated using logistic regression, adjusted for age and body mass index. Results: Overall, 35 patients (70 hips) with a mean age of 28.0 ± 2.0 years and mean body mass index of 24.1 ± 1.8 participated at 12-year follow-up. Cam morphology was present in 56 of 70 hips (80%). The prevalence of cartilage loss was 52% in hips with cam morphology and 21% in hips without cam morphology (adjusted odds ratio, 4.52 [95% CI, 1.16-17.61]; P =.03). A labral abnormality was present in 77% of hips with cam morphology and in 64% of hips without cam morphology (adjusted odds ratio, 1.99 [95% CI, 0.59-6.73]; P =.27). The duration of cam morphology did not influence these associations. Conclusion: The development of cam morphology during skeletal growth was associated with future magnetic resonance imaging findings consistent with cartilage loss in young adults but not with labral abnormalities.</p

Pharmacokinetic Targets for Therapeutic Drug Monitoring of Small Molecule Kinase Inhibitors in Pediatric Oncology

In recent years new targeted small molecule kinase inhibitors have become available for pediatric patients with cancer. Relationships between drug exposure and treatment response have been established for several of these drugs in adults. Following these exposure–response relationships, pharmacokinetic (PK) target minimum plasma rug concentration at the end of a dosing interval (Cmin) values to guide therapeutic drug monitoring (TDM) in adults have been proposed. Despite the fact that variability in PK may be even larger in pediatric patients, TDM is only sparsely applied in pediatric oncology. Based on knowledge of the PK, mechanism o

The Luxembourg Parkinson's study: A comprehensive approach for stratification and early diagnosis

While genetic advances have successfully defined part of the complexity in Parkinson's disease (PD), the clinical characterization of phenotypes remains challenging. Therapeutic trials and cohort studies typically include patients with earlier disease stages and exclude comorbidities, thus ignoring a substantial part of the real-world PD population. To account for these limitations, we implemented the Luxembourg PD study as a comprehensive clinical, molecular and device-based approach including patients with typical PD and atypical parkinsonism, irrespective of their disease stage, age, comorbidities, or linguistic background. To provide a large, longitudinally followed, and deeply phenotyped set of patients and controls for clinical and fundamental research on PD, we implemented an open-source digital platform that can be harmonized with international PD cohort studies. Our interests also reflect Luxembourg-specific areas of PD research, including vision, gait, and cognition. This effort is flanked by comprehensive biosampling efforts assuring high quality and sustained availability of body liquids and tissue biopsies. We provide evidence for the feasibility of such a cohort program with deep phenotyping and high quality biosampling on parkinsonism in an environment with structural specificities and alert the international research community to our willingness to collaborate with other centers. The combination of advanced clinical phenotyping approaches including device-based assessment will create a comprehensive assessment of the disease and its variants, its interaction with comorbidities and its progression. We envision the Luxembourg Parkinson's study as an important research platform for defining early diagnosis and progression markers that translate into stratified treatment approaches

Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI

Background: As differentiating between lipomas and atypical lipomatous tumors (ALTs) based on imaging is challenging and requires biopsies, radiomics has been proposed to aid the diagnosis. This study aimed to externally and prospectively validate a radiomics model differentiating between lipomas and ALTs on MRI in three large, multi-center cohorts, and extend it with automatic and minimally interactive segmentation methods to increase clinical feasibility. Methods: Three study cohorts were formed, two for external validation containing data from medical centers in the United States (US) collected from 2008 until 2018 and the United Kingdom (UK) collected from 2011 until 2017, and one for prospective validation consisting of data collected from 2020 until 2021 in the Netherlands. Patient characteristics, MDM2 amplification status, and MRI scans were collected. An automatic segmentation method was developed to segment all tumors on T1-weighted MRI scans of the validation cohorts. Segmentations were subsequently quality scored. In case of insufficient quality, an interactive segmentation method was used. Radiomics performance was evaluated for all cohorts and compared to two radiologists. Findings: The validation cohorts included 150 (54% ALT), 208 (37% ALT), and 86 patients (28% ALT) from the US, UK and NL. Of the 444 cases, 78% were automatically segmented. For 22%, interactive segmentation was necessary due to insufficient quality, with only 3% of all patients requiring manual adjustment. External validation resulted in an AUC of 0.74 (95% CI: 0.66, 0.82) in US data and 0.86 (0.80, 0.92) in UK data. Prospective validation resulted in an AUC of 0.89 (0.83, 0.96). The radiomics model performed similar to the two radiologists (US: 0.79 and 0.76, UK: 0.86 and 0.86, NL: 0.82 and 0.85). Interpretation: The radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics. Funding: Hanarth fonds.</p

Minimally interactive segmentation of soft-tissue tumors on CT and MRI using deep learning

BACKGROUND: Segmentations are crucial in medical imaging for morphological, volumetric, and radiomics biomarkers. Manual segmentation is accurate but not feasible in clinical workflow, while automatic segmentation generally performs sub-par.PURPOSE: To develop a minimally interactive deep learning-based segmentation method for soft-tissue tumors (STTs) on CT and MRI.MATERIAL AND METHODS: The interactive method requires the user to click six points near the tumor's extreme boundaries in the image. These six points are transformed into a distance map and serve, with the image, as input for a convolutional neural network. A multi-center public dataset with 514 patients and nine STT phenotypes in seven anatomical locations, with CT or T1-weighted MRI, was used for training and internal validation. For external validation, another public dataset was employed, which included five unseen STT phenotypes in extremities on CT, T1-weighted MRI, and T2-weighted fat-saturated (FS) MRI.RESULTS: Internal validation resulted in a dice similarity coefficient (DSC) of 0.85 ± 0.11 (mean ± standard deviation) for CT and 0.84 ± 0.12 for T1-weighted MRI. External validation resulted in DSCs of 0.81 ± 0.08 for CT, 0.84 ± 0.09 for T1-weighted MRI, and 0.88 ± 0.08 for T2-weighted FS MRI. Volumetric measurements showed consistent replication with low error internally (volume: 1 ± 28 mm 3, r = 0.99; diameter: - 6 ± 14 mm, r = 0.90) and externally (volume: - 7 ± 23 mm 3, r = 0.96; diameter: - 3 ± 6 mm, r = 0.99). Interactive segmentation time was considerably shorter (CT: 364 s, T1-weighted MRI: 258s) than manual segmentation (CT: 1639s, T1-weighted MRI: 1895s). CONCLUSION: The minimally interactive segmentation method effectively segments STT phenotypes on CT and MRI, with robust generalization to unseen phenotypes and imaging modalities.KEY POINTS: Question Can this deep learning-based method segment soft-tissue tumors faster than can be done manually and more accurately than other automatic methods? Findings The minimally interactive segmentation method achieved accurate segmentation results in internal and external validation, and generalized well across soft-tissue tumor phenotypes and imaging modalities. Clinical relevance This minimally interactive deep learning-based segmentation method could reduce the burden of manual segmentation, facilitate the integration of imaging-based biomarkers (e.g., radiomics) into clinical practice, and provide a fast, semi-automatic solution for volume and diameter measurements (e.g., RECIST).</p

Prevalence, incidence, and progression of hip osteoarthritis in a young military population: The ADVANCE cohort study

Objective: Prevalence of hip osteoarthritis (OA) is rarely reported in young populations (e.g., military). We will report the prevalence of hip OA in a young military cohort and investigate the relationship between injury and progression/incidence. Design: ADVANCE is a prospective cohort study comparing physical and psychosocial outcomes in 1145 men who served in Afghanistan including 579 men with combat injury (Exposed) who were frequency-matched to 566 controls (Unexposed). The Exposed group was sub-divided into hip injured (Exp-H), lower limb amputation (Exp-A) and other (Exp-NA). Kellgren-Lawrence (KL) scores of pelvic radiographs and Non-Arthritic Hip Score (NAHS) questionnaires were collected across two waves (Baseline and Follow-up). Prevalence at Baseline (KL ​≥ ​2), progression (KL ​≥ ​1 ​at Baseline, KL ​≥ ​2 ​at Follow-up) and incidence (KL0 at Baseline, KL ​≥ ​2 ​at Follow-up) at Follow-up were reported and compared between groups for KL and NAHS. Results: Baseline prevalence of radiographic hip OA was 8.5 ​% and 4.4 ​% in the Exposed and Unexposed groups, respectively. Exp-A and Exp-H groups had 3.88 (95%CI:2.27–6.63) and 7.18 (95%CI:3.44–14.98 times increased risk for radiographic hip OA than Unexposed. Exp-A and Exp-H had a 2.15 (95%CI:1.22–3.80) and 3.28 (95%CI:1.42–7.59) times increased radiographic progression risk, compared to Unexposed. Risk of NAHS Progression and Incidence were not significantly different between groups. Conclusion: Radiographic hip OA prevalence is higher in a young military population than in a similarly aged general population. Combat injury alone may not increase hip OA prevalence; but hip and lower limb loss injuries do. Progression risk is highest in those with hip or limb loss injuries