Heterogeneous melting near the Thwaites Glacier grounding line.

Thwaites Glacier represents 15% of the ice discharge from the West Antarctic Ice Sheet and influences a wider catchment1-3. Because it is grounded below sea level4,5, Thwaites Glacier is thought to be susceptible to runaway retreat triggered at the grounding line (GL) at which the glacier reaches the ocean6,7. Recent ice-flow acceleration2,8 and retreat of the ice front8-10 and GL11,12 indicate that ice loss will continue. The relative impacts of mechanisms underlying recent retreat are however uncertain. Here we show sustained GL retreat from at least 2011 to 2020 and resolve mechanisms of ice-shelf melt at the submetre scale. Our conclusions are based on observations of the Thwaites Eastern Ice Shelf (TEIS) from an underwater vehicle, extending from the GL to 3 km oceanward and from the ice-ocean interface to the sea floor. These observations show a rough ice base above a sea floor sloping upward towards the GL and an ocean cavity in which the warmest water exceeds 2 °C above freezing. Data closest to the ice base show that enhanced melting occurs along sloped surfaces that initiate near the GL and evolve into steep-sided terraces. This pronounced melting along steep ice faces, including in crevasses, produces stratification that suppresses melt along flat interfaces. These data imply that slope-dependent melting sculpts the ice base and acts as an important response to ocean warming.

r-Process elements from magnetorotational hypernovae.

Neutron-star mergers were recently confirmed as sites of rapid-neutron-capture (r-process) nucleosynthesis1-3. However, in Galactic chemical evolution models, neutron-star mergers alone cannot reproduce the observed element abundance patterns of extremely metal-poor stars, which indicates the existence of other sites of r-process nucleosynthesis4-6. These sites may be investigated by studying the element abundance patterns of chemically primitive stars in the halo of the Milky Way, because these objects retain the nucleosynthetic signatures of the earliest generation of stars7-13. Here we report the element abundance pattern of the extremely metal-poor star SMSS J200322.54-114203.3. We observe a large enhancement in r-process elements, with very low overall metallicity. The element abundance pattern is well matched by the yields of a single 25-solar-mass magnetorotational hypernova. Such a hypernova could produce not only the r-process elements, but also light elements during stellar evolution, and iron-peak elements during explosive nuclear burning. Hypernovae are often associated with long-duration γ-ray bursts in the nearby Universe8. This connection indicates that similar explosions of fast-spinning strongly magnetized stars occurred during the earliest epochs of star formation in our Galaxy.

Reliability and reference values for diaphragmatic excursion, thickness, and thickening fraction and quadriceps femoris muscle thickness in full-term newborns evaluated by ultrasound.

To determine the diaphragm thickness, thickening fraction, and excursion and thickness of the quadriceps femoris muscle in full-term newborns and to evaluate the intra- and interrater reliability of these measurements. This was a prospective, observational clinical study including full-term newborns born within the first 48 h after birth. Serial measurements of the thickness, thickening fraction, and mobility of the diaphragm muscles and the thickness of the quadriceps muscle were obtained using ultrasound images. A total of 69 newborns with a mean gestational age of 39 weeks were included. The following measurements were obtained and are expressed as the mean (standard deviation): inspiratory diaphragm thickness, 0.19 cm (0.04); expiratory diaphragm thickness, 0.16 cm (0.04); diaphragm thickness fraction, 16.70 cm (10.27); diaphragmatic excursion, 0.68 cm (0.22); and quadriceps thickness, 0.99 cm (0.14). Intrarater reliability was assessed using intraclass correlation coefficients (ICCs). Excellent intrarater agreement was observed for the two groups of operators (ICC > 0.86, p < 0.001) for all measurements except for the diaphragm thickening fraction, which showed good agreement for both operator groups (ICC = 0.70, p < 0.001). Regarding interrater reliability, moderate agreement between the raters was observed in the means of all measures (ICC > 0.49, p < 0.001), except for the diaphragm thickening fraction, which showed poor agreement.    Conclusion: Good intrarater and moderate interrater reliability were achieved in ultrasound evaluations of the thickness and mobility of the diaphragm and quadriceps femoris muscles in full-term newborns, demonstrating the feasibility of this technique for clinical use. This pioneering study offers reference values for these muscles in a single study, allowing comparisons between different clinical conditions. What is Known: • Ultrasound is a highly reliable tool for muscle assessment that can be used to assess muscular atrophy in critically ill patients. • Muscle atrophy worsens the patient's condition and has been associated with worse outcomes. What is New: • To our knowledge, this is the first study to jointly evaluate the diaphragm and quadriceps muscle thickness and evaluate the reliability of all measurements. • Our study presents reference values for both muscles, enabling comparisons between different clinical conditions.

Migraine or any headaches and white matter hyperintensities and their progression in women and men.

BACKGROUND: Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders. METHODS: Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2-3 vs. 0-1) by log-binomial regression, adjusted for confounders. RESULTS: The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454-6880) mm3 in women and 4812 (2842-8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache. CONCLUSIONS: Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research.

Accuracy of the sonographic determination of estimated fetal weight in anhydramnios.

OBJECTIVE: To determine whether the presence of anhydramnios significantly influences the sonographic estimated fetal weight (EFW) compared to a matched cohort with normal amniotic fluid volume. METHODS: The study sample of this retrospective case-control study consisted of 114 pregnant women who presented to a Tertiary Perinatal Clinic between 2015 and 2020. 57 of them presented with an anhydramnios and a matched cohort of 57 women with normal amniotic fluid volume. At time of admission, gestational age varied between 22 + 4 and 42 + 6 weeks of pregnancy. All women underwent detailed ultrasound assessment for EFW and amniotic fluid index. To determine EFW Hadlock's estimation formula I was used which is based on measurements of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). The EFW was compared with the weight at delivery. The maximum time interval between measurement and delivery was 5 days. RESULTS: There was neither a significant difference between the case and control group with regard to gestational age at ultrasound in days (median 249 days and 246 days, p = 0.97), nor to gestational age at birth (median 249 days and 247 days, p = 0.98). Concerning the newborns parameters, the body length at birth was not significantly different between the case and control group in centimeters (cm) (median 47 cm and 47 cm, p = 0.79). EFW in gram (g) was lower than birth weight in both groups and did not differ significantly between case and control group (estimated weight median 2247 g and 2421 g, p = 0.46; birth weight median 2440 g and 2475 g, p = 0.47). The difference between EFW and birth weight in percent (%) did not differ between the case and control group (median - 3.9% and - 5.6%, p = 0.70). The maternal parameters showed that the patients in the case group were younger (median 31 years and 38 years p = 0.20) and had a significantly higher body mass index (BMI) (median 27.3 kg/m2 vs 22.0 kg/m2, < 0.001) compared to the control group. CONCLUSION: Our study shows for the first time that EFW in women with anhydramnios can be determined sonographically just as accurately as in a matched cohort with normal amniotic fluid volume. A reliable estimation of fetal weight is crucial for optimal assessment of the newborns prognosis and counseling of the parents especially when advising women in the early weeks of pregnancy at the limit of viability.

Course of the sFlt-1/PlGF ratio in fetal growth restriction and correlation with biometric measurements, feto-maternal Doppler parameters and time to delivery.

PURPOSE: The study aimed to assess the course of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in pregnant women with fetal growth restriction (FGR) and to evaluate potential associations between the sFlt-1/PlGF ratio and feto-maternal Doppler parameters, fetal biometric measurements and the time between study inclusion and birth ("time to delivery"). METHODS: This was a retrospective longitudinal single center study including 52 FGR cases. The serum levels of sFlt-1 and PlGF were measured by using the BRAHMS Kryptor Compact PLUS. Fetal biometric and Doppler parameters, as well as the sFlt-1/PlGF ratio, were obtained both upon study inclusion and upon birth. RESULTS: Various associations between the levels of the biomarkers in maternal blood upon study inclusion and upon birth and sonographic parameters were observed in FGR cases: umbilical artery (p < 0.01), uterine arteries (p < 0.01), ductus venosus (p < 0.05), cerebroplacental ratio (CPR) (p < 0.01), femur length (p < 0.01) and birth weight (p < 0.01). The higher the sFlt-1/PlGF ratio upon study inclusion, the shorter the "time to delivery" (p < 0.01). The multivariate regression analysis showed that the greater the daily percentage increase of the angiogenic markers, the shorter the "time to delivery" (p < 0.01). CONCLUSION: The fetal well-being, as measured by feto-maternal Doppler parameters such as CPR and the severity of the placental dysfunction, as measured by the urgency of birth and birth weight, is reflected by the level of the sFlt-1/PlGF ratio in the maternal serum. A rapid daily increase of the sFlt-1/PlGF ratio is significantly associated with the clinical progression of the disease.

Prediction of future cardiovascular events by Framingham, SCORE and asCVD risk scores is less accurate in HIV-positive individuals from the HIV-HEART Study compared with the general population.

OBJECTIVES: Cardiovascular diseases (CVDs) occur more often in people living with HIV (PLWH) than in the general population. It has been reported that CVD risk scores developed for the general population underestimate the CVD risk in PLWH. Performances of the Framingham Risk Score (FRS), the Systematic Coronary Risk Evaluation (SCORE) and the atherosclerotic cardiovascular disease (asCVD) risk score in PLWH were compared with the general population to quantify score-specific differences in risk prediction. METHODS: HIV-positive outpatients from the HIV-HEART (HIVH) study (n = 567) were compared with participants from the population-based Heinz Nixdorf Recall (HNR) study (n ~ 4440) both recruited from the German Ruhr area. During a follow-up time of around 5 years, the associations between the FRS and incident CVD and peripheral artery disease (CVD_pAD), SCORE and coronary heart disease (CHD), and asCVD and incident CVD were examined using logistic regression. Score performances were assessed by comparing the areas under the curve (AUCs). RESULTS: The mean ages were 52.9 ± 6.7 and 59.1 ± 7.7 years in the HIVH and HNR studies, respectively. There were fewer incident CVD events in the HNR study than in the HIVH study (CVD_pAD: 3.9% vs. 12.1%; CHD: 2.1% vs. 7.8%; CVD: 3.5% vs. 9.9%). Age- and sex-adjusted CVD risk was greater with increasing FRS, SCORE and asCVD in both cohorts, but the scores performed more accurately in the HNR than in HIVH study (AUCs FRS: 0.71 vs. 0.65; SCORE: 0.70 vs. 0.62; asCVD: 0.74 vs. 0.62). CONCLUSIONS: Associations between risk scores and future CVD were observed in both cohorts, but the score performances were less reliable in PLWH than in the general population.

70 mJ nonlinear compression and scaling route for an Yb amplifier using large-core hollow fibers.

In this Letter, we investigate the energy-scaling rules of hollow-core fiber (HCF)-based nonlinear pulse propagation and compression merged with high-energy Yb-laser technology, in a regime where the effects such as plasma disturbance, optical damages, and setup size become important limiting parameters. As a demonstration, 70 mJ 230 fs pulses from a high-energy Yb laser amplifier were compressed down to 40 mJ 25 fs by using a 2.8-m-long stretched HCF with a core diameter of 1 mm, resulting in a record peak power of 1.3 TW. This work presents a critical advance of a high-energy pulse (hundreds of mJ level) nonlinear interactions platform based on high energy sub-ps Yb technology with considerable applications, including driving intense THz, X-ray pulses, Wakefield acceleration, parametric wave mixing and ultraviolet generation, and tunable long-wavelength generation via enhanced Raman scattering.

Energy-Spread Preservation and High Efficiency in a Plasma-Wakefield Accelerator.

Energy-efficient plasma-wakefield acceleration of particle bunches with low energy spread is a promising path to realizing compact free-electron lasers and particle colliders. High efficiency and low energy spread can be achieved simultaneously by strong beam loading of plasma wakefields when accelerating bunches with carefully tailored current profiles [M. Tzoufras et al., Phys. Rev. Lett. 101, 145002 (2008)PRLTAO0031-900710.1103/PhysRevLett.101.145002]. We experimentally demonstrate such optimal beam loading in a nonlinear electron-driven plasma accelerator. Bunches with an initial energy of 1 GeV were accelerated by 45 MeV with an energy-transfer efficiency of (42±4)% at a gradient of 1.3 GV/m while preserving per-mille energy spreads with full charge coupling, demonstrating wakefield flattening at the few-percent level.

Health-related quality of life in patients with untreated cavernous malformations of the central nervous system.

BACKGROUND AND PURPOSE: To estimate health-related quality of life (HRQOL) in patients with untreated cavernous malformation of the CNS [cavernous cerebral malformations (CCMs)]. METHODS: We performed a cross-sectional observational study on patients with CCMs admitted to our department from 1 November 2017 to 10 January 2020 using standardized interviews [short-form-36 questionnaire, hospital anxiety and depression score (HADS-A/D), CCM perception questionnaire]. Included criteria were diagnosis of an untreated CCM and information about the diagnosis in a specialized CCM consultation. Health-related quality of life (HRQOL) data were analyzed and compared to the German normal population. Uni- and multivariate analyses were carried out to identify variables with impact on outcome. RESULTS: Two hundred nineteen (93%) of 229 eligible patients were included. Mean age was 46.3 ± 14.7 (18-86) years; 136 (62%) were female. Ninety-eight (45%) patients presented with symptomatic hemorrhage (SH), and 17 (8%) with repetitive SH. Ninety-two (42%) patients were asymptomatic. Thirty-seven patients (17%) suffered from cavernoma-related epilepsy. Twenty-eight patients (13%) suffered from familial CCMs. Patients showed significantly decreased component scores and subdomain scores compared to the normal population, with effects ranging from small to large. This accounted largely also for asymptomatic patients (except for physical component score and main physical subdomains). Multivariate regression analysis confirmed impact of functional impairment on physical component score. HADS-A was significantly increased. HADS-A/D strongly correlated with mental component score and individual perception of the CCM. CONCLUSIONS: Patients with the diagnosis of a CCM showed decreased HRQOL compared to the normal population even when not suffering functional impairment or neurological symptoms. Our data may function as benchmarks in evaluation of different (future) management strategies.

Linking high harmonics from gases and solids.

When intense light interacts with an atomic gas, recollision between an ionizing electron and its parent ion creates high-order harmonics of the fundamental laser frequency. This sub-cycle effect generates coherent soft X-rays and attosecond pulses, and provides a means to image molecular orbitals. Recently, high harmonics have been generated from bulk crystals, but what mechanism dominates the emission remains uncertain. To resolve this issue, we adapt measurement methods from gas-phase research to solid zinc oxide driven by mid-infrared laser fields of 0.25 volts per ångström. We find that when we alter the generation process with a second-harmonic beam, the modified harmonic spectrum bears the signature of a generalized recollision between an electron and its associated hole. In addition, we find that solid-state high harmonics are perturbed by fields so weak that they are present in conventional electronic circuits, thus opening a route to integrate electronics with attosecond and high-harmonic technology. Future experiments will permit the band structure of a solid to be tomographically reconstructed.

Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way.

The first stars are predicted to have formed within 200 million years after the Big Bang, initiating the cosmic dawn. A true first star has not yet been discovered, although stars with tiny amounts of elements heavier than helium ('metals') have been found in the outer regions ('halo') of the Milky Way. The first stars and their immediate successors should, however, preferentially be found today in the central regions ('bulges') of galaxies, because they formed in the largest over-densities that grew gravitationally with time. The Milky Way bulge underwent a rapid chemical enrichment during the first 1-2 billion years, leading to a dearth of early, metal-poor stars. Here we report observations of extremely metal-poor stars in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than the solar value without noticeable carbon enhancement. We confirm that most of the metal-poor bulge stars are on tight orbits around the Galactic Centre, rather than being halo stars passing through the bulge, as expected for stars formed at redshifts greater than 15. Their chemical compositions are in general similar to typical halo stars of the same metallicity although intriguing differences exist, including lower abundances of carbon.

Sublimation in bright spots on (1) Ceres.

The dwarf planet (1) Ceres, the largest object in the main asteroid belt with a mean diameter of about 950 kilometres, is located at a mean distance from the Sun of about 2.8 astronomical units (one astronomical unit is the Earth-Sun distance). Thermal evolution models suggest that it is a differentiated body with potential geological activity. Unlike on the icy satellites of Jupiter and Saturn, where tidal forces are responsible for spewing briny water into space, no tidal forces are acting on Ceres. In the absence of such forces, most objects in the main asteroid belt are expected to be geologically inert. The recent discovery of water vapour absorption near Ceres and previous detection of bound water and OH near and on Ceres (refs 5-7) have raised interest in the possible presence of surface ice. Here we report the presence of localized bright areas on Ceres from an orbiting imager. These unusual areas are consistent with hydrated magnesium sulfates mixed with dark background material, although other compositions are possible. Of particular interest is a bright pit on the floor of crater Occator that exhibits probable sublimation of water ice, producing haze clouds inside the crater that appear and disappear with a diurnal rhythm. Slow-moving condensed-ice or dust particles may explain this haze. We conclude that Ceres must have accreted material from beyond the 'snow line', which is the distance from the Sun at which water molecules condense.

Blood Flow Velocimetry in a Microchannel During Coagulation Using Particle Image Velocimetry and Wavelet-Based Optical Flow Velocimetry.

This article describes novel measurements of the velocity of whole blood flow in a microchannel during coagulation. The blood is imaged volumetrically using a simple optical setup involving a white light source and a microscope camera. The images are processed using particle image velocimetry (PIV) and wavelet-based optical flow velocimetry (wOFV), both of which use images of individual blood cells as flow tracers. Measurements of several clinically relevant parameters such as the clotting time, decay rate, and blockage ratio are computed. The high-resolution wOFV results yield highly detailed information regarding thrombus formation and corresponding flow evolution that is the first of its kind.

[Clinical Course of Typical and Atypical Carcinoids (bpNET): Evaluation of PneuNET Register Berlin Data for the Identification of Indicators for Prognosis Determination and Therapy Planning]. / Klinischer Verlauf typischer und atypischer Karzinoide (bpNET) ­ Auswertung von Registerdaten des PneuNET-Registers Berlin zur Identifikation von Indikatoren zur Prognosebestimmung und Therapieplanung.

AIM: Retrospective analysis of data from PneuNET registry to evaluate clinical follow up of patients with typical and atypical bronchopulmonary carcinoid (bpNET). METHOD: Three lung cancer centres in Berlin included patients in the registry between 2007 and 2016. Inclusion criteria were: diagnosis of typical or atypical carcinoid, age > 18 years, follow-up for not less than 2 years. Frequency, gender, functional status, smoking status, localisation of the tumour, biomarker, diagnostic and therapeutic procedures and follow-up were evaluated. RESULTS: Since 01. 01. 2007, 187 patients with bronchopulmonary carcinoid had been included in the registry. The ratio between TC and AC was 8:2. The median age was 65.4 years and 64 % of patients were women. 10.7 % of patients had pulmonary symptoms, 2 patients a carcinoid syndrome, no patient was detected with MEN-1-syndrome. 87.7 % of patients had undergone surgery, 69.5 % as lobectomy with systematic lymphadenectomy. Only 10 % of patients were diagnosed with Stage IV disease, with atypical carcinoid predominating Systemic therapies included chemotherapy, everolimus and somatostatin analogues. CONCLUSION: Bronchopulmonary carcinoids are well differentiated tumours of the lung. The early stage diagnosis offers the possibility of local therapy with excellent prognosis. We have improved systemic treatment options with mTOR-inhibitor everolimus and somatostatin analogues also in advanced stage of the disease. Because of the rareness of this heterogenous group of tumours, it is meaningful to collect data systematically in order to have a standardised algorithm of diagnostic procedures and therapy assessment.

Model-based evaluation of the efficacy and safety of nivolumab once every 4 weeks across multiple tumor types.

BACKGROUND: Nivolumab 480 mg every 4 weeks (Q4W) is approved in the European Union, United States, and several other markets across multiple tumor types. Its approval was supported by quantitative efficacy/safety analyses bridging to 3 mg/kg every 2 weeks (Q2W). PATIENTS AND METHODS: The benefit-risk profile of nivolumab 480 mg Q4W relative to 3 mg/kg Q2W was evaluated using population pharmacokinetic modeling and exposure-response (E-R) analyses for safety and efficacy. Pharmacokinetic exposures were predicted for 3203 patients with melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), squamous cell carcinoma of the head and neck, urothelial carcinoma, or classical Hodgkin lymphoma. Quantitative models analyzed E-R to predict 480-mg Q4W safety across all indications and efficacy for melanoma, NSCLC, and RCC. Intratumoral receptor occupancy (RO) was predicted for parameters representing different tumor types. RESULTS: Time-averaged concentrations for 480 mg Q4W versus 3 mg/kg Q2W were higher during the first 28 days (26.8%) and similar at steady state (5.2%). The maximum concentration (Cmax) after the first dose was higher (110.4%), and the trough concentration at day 28 was lower (-22.1%) with 480 mg Q4W versus 3 mg/kg Q2W. The Cmax achieved with 480 mg Q4W was lower than the previously established safe dose of 10 mg/kg Q2W. The probability of adverse events for key safety end points was similar for 480 mg Q4W and 3 mg/kg Q2W. The predicted overall survival and objective response rates with 480 mg Q4W were comparable to 3 mg/kg Q2W. The predicted high intratumoral RO provided additional evidence to support 480 mg Q4W across tumor types. CONCLUSIONS: The benefit-risk profile for nivolumab 480 mg Q4W was predicted to be similar to that of 3 mg/kg Q2W across tumor types while providing a convenient and flexible option for patients and their caregivers.

No longer a historical ailment: two cases of childhood scurvy with recommendations for bone health providers.

PURPOSE: Scurvy, due to vitamin C deficiency, is commonly referenced as a "forgotten" or "historical" disease. A growing number of case reports challenge this notion. Bone health providers are often consulted early in the presentation of scurvy to evaluate musculoskeletal complaints resulting from impaired collagen production and disrupted endochondral bone formation. In this report, we describe two cases of childhood scurvy. Our objective is to summarize the key features of scurvy for bone health providers, with the goal of raising awareness and facilitating diagnosis in future cases. CASE DESCRIPTIONS: Case one occurred in a 12-year-old non-verbal, non-ambulatory female on a ketogenic diet for refractory epilepsy. Clinical findings included hemarthrosis, transfusion dependent anemia, elevated inflammatory markers, and epiphysiolysis. Magnetic resonance imaging (MRI) revealed multi-focal bone marrow signal abnormalities and physeal irregularities. Case two occurred in a typically developing 5-year-old male presenting with limp and knee pain. Symptoms progressed despite casting and immobilization. Mild anemia, elevated inflammatory markers, and multi-focal marrow and physeal MRI abnormalities were identified. Subsequent dietary history revealed total absence of fruit or vegetable consumption. The diagnosis of scurvy was confirmed in both cases by undetectable plasma vitamin C concentrations. Treatment with vitamin C led to rapid clinical improvement. CONCLUSION: Scurvy can no longer be considered a historical diagnosis and should not be forgotten when evaluating children with musculoskeletal ailments. Early recognition of the signs, symptoms, and imaging findings of scurvy can reduce the clinical burden of this disease with the timely initiation of vitamin C therapy.

High-field mid-infrared pulses derived from frequency domain optical parametric amplification.

We present a novel, to the best of our knowledge, approach for scaling the peak power of mid-infrared laser pulses with few-cycle duration and carrier-to-envelope phase stabilization. Using frequency domain optical parametric amplification (FOPA), selective amplification is performed on two spectral slices of broadband pulses centered at 1.8 µm wavelength. In addition to amplification, the Fourier plane is used for specific pulse shaping to control both the relative polarization and the phase/delay between the two spectral slices of the input pulses. At the output of the FOPA, intrapulse difference frequency generation provides carrier-envelope phase stabilized two-cycle pulses centered at 9.5 µm wavelength with 25.5 µJ pulse energy. The control of the carrier-envelope phase is demonstrated through the dependence of high-harmonic generation in solids. This architecture is perfectly adapted to be scaled in the future to high average and high peak powers using picosecond ytterbium laser technologies.

High energy redshifted and enhanced spectral broadening by molecular alignment.

We demonstrate an efficient approach for enhancing the spectral broadening of long laser pulses and for efficient frequency redshifting by exploiting the intrinsic temporal properties of molecular alignment inside a gas-filled hollow-core fiber (HCF). We find that laser-induced alignment with durations comparable to the characteristic rotational time scale TRotAlign enhances the efficiency of redshifted spectral broadening compared to noble gases. The applicability of this approach to Yb lasers with (few hundred femtoseconds) long pulse duration is illustrated, for which efficient broadening based on conventional Kerr nonlinearity is challenging to achieve. Furthermore, this approach proposes a practical solution for high energy broadband long-wavelength light sources, and it is attractive for many strong field applications.