A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.

Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94R⊕ to 2.85R⊕. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.

Reanalysis of the ß-ν[over ¯]_{e} Angular Correlation Measurement from the aSPECT Experiment with New Constraints on Fierz Interference.

On the basis of revisions of some of the systematic errors, we reanalyzed the electron-antineutrino angular correlation (a coefficient) in free neutron decay inferred from the recoil energy spectrum of the protons which are detected in 4π by the aSPECT spectrometer. With a=-0.104 02(82) the new value differs only marginally from the one published in 2020. The experiment also has sensitivity to b, the Fierz interference term. From a correlated (b,a) fit to the proton recoil spectrum, we derive a limit of b=-0.0098(193) which translates into a somewhat improved 90% confidence interval region of -0.041≤b≤0.022 on this hypothetical term. Tighter constraints on b can be set from a combined [shown as superscript (c)] analysis of the PERKEO III (ß asymmetry) and aSPECT measurement which suggests a finite value of b with b^{(c)}=-0.0181±0.0065 deviating by 2.82σ from the standard model.

Informed consent in gynecological oncology: a JAGO/NOGGO survey on real-world practices in daily clinical routine.

PURPOSE: Informed consent is a quintessential element of contemporary medicine, reflecting the fundamental right of patients to participate in decision-making regarding their health. Despite its critical importance, there is a lack of data on real-world practices regarding patient informed consent in the context of modern, high-pressure medical environments. METHODS: We conducted a multinational multicentric survey from February 24, 2022, to September 14, 2022, investigating the practices and challenges surrounding informed consent in hospitals across Germany, Austria, and Switzerland with the use of a specifically developed questionnaire. RESULTS: Drawing on over 200 responses from gynecologists, the survey shows a critical need for structured training in conducting informed consent discussions with over 80% of participants expressing interest in courses addressing this aspect. Notably, a considerable portion of the physicians (59.9%) reported conducting discussions on procedures they had never personally witnessed. Significant disparities between types of hospitals and professional groups were observed in the frequency of informed consent discussions, with limitations arising from factors such as time constraints, language barriers, and insufficient resources for patient education. Moreover, the psychological burden experienced by physicians after informed-consent discussions underscores the need for systemic changes to alleviate concerns regarding patient safety, legal repercussions, and patient satisfaction. CONCLUSION: This study serves as a call to action, emphasizing the need of enhancing resources and support for medical professionals to uphold the principles of empathic and comprehensive patient information and shared decision-making. TRIAL REGISTRY: DRKS00028295, 25.07.2024.

THz optical beat-note detection with a fast superconducting hot electron bolometer operating up to 31†GHz.

We study the performance of a hot-electron bolometer (HEB) operating at THz frequencies based on superconducting niobium nitride films. We report on the voltage response of the detector over a large electrical detection bandwidth carried out with different THz sources. We show that the impulse response of the fully packaged HEB at 7.5 K has a 3 dB cutoff around 2 GHz. Remarkably, detection capability is still observed above 30 GHz in an heterodyne beating experiment using a THz quantum cascade laser frequency comb. Additionally, the HEB sensitivity has been evaluated and an optical noise equivalent power NEP of 0.8 pW/√H z has been measured at 1 MHz.

Absolute frequency referencing in the long wave infrared using a quantum cascade laser frequency comb.

Optical frequency combs (OFCs) based on quantum cascade lasers (QCLs) have transformed mid-infrared spectroscopy. However, QCL-OFCs have not yet been exploited to provide a broadband absolute frequency reference. We demonstrate this possibility by performing comb-calibrated spectroscopy at 7.7 µm (1305 cm-1) using a QCL-OFC referenced to a molecular transition. We obtain 1.5·10-10 relative frequency stability (100-s integration time) and 3·10-9 relative frequency accuracy, comparable with state-of-the-art solutions relying on nonlinear frequency conversion. We show that QCL-OFCs can be locked with sub-Hz-level stability to a reference for hours, thus promising their use as metrological tools for the mid-infrared.

Urine and fecal excretion patterns of dairy cows divergent for milk urea nitrogen breeding values consuming either a plantain or ryegrass diet.

Environmental degradation has been attributed to inefficient nitrogen utilization from pastoral dairy production systems. This degradation has especially been associated with the urine patch, which has been identified as a key component of nitrate leaching to waterways. However, a lack of information exists regarding the pattern of urination events and individual urination characteristics across the day, which would help inform strategic management decisions. The aim of this study was therefore to evaluate and report the patterns and characteristics of fecal and urination events throughout the day for cows divergent for milk urea nitrogen breeding values (MUNBV) on either a plantain [Plantago lanceolata L. (PL)] or ryegrass [Lolium perenne L. (RG)] diet as ways to reduce environmental impact. Sixteen multiparous lactating Holstein Friesian × Jersey cows divergent for MUNBV were housed in metabolism crates for 72 h, with all excretion events captured and analyzed. Cows selected as low for MUNBV consistently had a 65.2-kg lower urinary urea nitrogen (UUN) load (kg/ha) than high MUNBV cows for all hours of the day when consuming RG. The association between lower urinary urea loading rates and less N leaching implies a reduced environmental impact from low MUNBV cows consuming RG. When cows consumed PL, regardless of MUNBV, they had on average a 137.5-kg (UUN/ha) lower loading rate compared with high MUNBV cows on RG and a 72.2-kg (UUN/ha) lower loading rate compared with low MUNBV cows consuming RG across the day. Cows on PL also exhibited a different diel pattern of UUN load compared with cows consuming RG. Differences in the diel pattern of N excreted in feces were also detected based on MUNBV and by diet, with low MUNBV cows excreting on average 3.06 g more N in feces per event for the majority of the day compared with high MUNBV cows when consuming RG. Lower UUN loading rates and more N excreted in feces indicate a potentially lower environmental impact from low MUNBV cows when consuming RG compared with high MUNBV cows. The use of the PL diet also resulted in lower UUN loading rates and greater levels of N excreted in feces compared with RG, therefore also indicating its ability to reduce environmental impact compared with RG.

Standardising clinical outcomes measures for adult clinical trials in Fabry disease: A global Delphi consensus.

BACKGROUND: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. METHODS AND FINDINGS: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial. CONCLUSION: This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution.

Coherently-averaged dual comb spectrometer at 7.7†µm with master and follower quantum cascade lasers.

We demonstrate coherent averaging of the multi-heterodyne beat signal between two quantum cascade laser frequency combs in a master-follower configuration. The two combs are mutually locked by acting on the drive current to control their relative offset frequency and by radio-frequency extraction and injection locking of their intermode beat signal to stabilize their mode spacing difference. By implementing an analog common-noise subtraction scheme, a reduction of the linewidth of all heterodyne beat notes by five orders of magnitude is achieved compared to the free-running lasers. We compare stabilization and post-processing corrections in terms of amplitude noise. While they give similar performances in terms of signal-to-noise ratio, real-time processing of the stabilized signal is less demanding in terms of computational power. Lastly, a proof-of-principle spectroscopic measurement was performed, showing the possibility to reduce the amount of data to be processed by three orders of magnitude, compared to the free-running system.

Magnetic deflection of neutral sodium-doped ammonia clusters.

We describe the setup and the performance of a new pulsed Stern-Gerlach deflector and present results for small sodium-doped ammonia clusters Na(NH3)n (n = 1-4) in a molecular beam. NaNH3 shows the expected deflection of a spin ½ system, while all lager clusters show much smaller deflections. Experimental deflection ratios are compared with the values calculated from molecular dynamics simulations. The comparison reveals that intracluster spin relaxation in NaNH3 takes place on a time scale significantly longer than 200 µs. Assuming that intracluster relaxation is the cause of the reduced deflection, relaxation times seem to be on the order of 200 µs for all larger clusters Na(NH3)n (n = 2-4). Our work is a first attempt to understand the magnetic properties of isolated, weakly-bound clusters with relevance to the variety of diamagnetic and paramagnetic species expected in solvated electron systems.

Rumen function and grazing behavior of early-lactation dairy cows supplemented with fodder beet.

Fodder beet (FB) is a source of readily fermentable carbohydrate that can mitigate early spring herbage deficits and correct the negative energy balance experienced during early lactation in pastoral dairy systems of New Zealand. However, the low-fiber and high-soluble carbohydrate content of both FB bulb and spring herbage are factors that promote subacute ruminal acidosis, impairing rumen function and limiting the marginal milk production response to supplement. In a crossover experiment, 8 Holstein Friesian × Jersey early-lactation dairy cows were used to test the effect of supplementing 16 kg of dry matter (DM) of a grazed perennial ryegrass herbage with 6 kg of DM/d of FB bulb (FBH) versus herbage only (HO) on changes in rumen function and grazing behavior. Following 20 d of adaptation to diets, DM disappearance (%) of FB bulb (FBH cows only) and herbage were measured in sacco, separately. Cows were fasted overnight, and the ruminal contents were bailed the following morning (~0930 h) again to determine the pool size of volatile fatty acids, ammonia, and particle size of digesta, as well as to estimate the rate of ruminal outflow and degradation of neutral detergent fiber. The FBH diet did not alter DM intake, milk yield, or milk solid (fat + protein) production compared with HO. Supplementation of herbage with FB reduced ruminal pH compared with HO between ~0800 h and 1300 h each day. During each period, 1 cow experienced severe subacute ruminal acidosis (pH <5.6 for >180 min/d) during final adaptation to the target FB allocation. The FBH diet reduced the ruminal pool of acetate and ammonia, but increased the ruminal pool of butyrate and lactate compared with HO. When fed FB, rumination and grazing time increased and grazing intensity declined compared with cows fed HO. Despite increased rumination, the comminution of large particles declined 28% between the first and second rumen bailing when cows were fed FB, and in sacco DM disappearance of perennial ryegrass declined 18% compared with cows fed HO. These results indicate that grazing dairy cows supplemented with FB (40% of daily intake) increase rumination and mastication intensity to counteract reduced ruminal degradation of ryegrass herbage due to low ruminal fluid pH.

Accurate ground state potential of Cu2 up to the dissociation limit by perturbation assisted double-resonant four-wave mixing.

Perturbation facilitated double-resonant four-wave mixing is applied to access high-lying vibrational levels of the X 1Σg + (0g +) ground state of Cu2. Rotationally resolved transitions up to v″ = 102 are measured. The highest observed level is at 98% of the dissociation energy. The range and accuracy of previous measurements are significantly extended. By applying the near dissociation equation developed by Le Roy [R. J. Le Roy, J. Quant. Spectrosc. Radiat. Transfer 186, 197 (2017)], a dissociation energy of De = 16 270(7) hc cm-1 is determined, and an accurate potential energy function for the X 1Σg + (0g +) ground state is obtained. Molecular constants are determined from the measured transitions and by solving the radial Schrödinger equation using this function and are compared with results from earlier measurements. In addition, benchmark multi-reference configuration interaction computations are performed using the Douglas-Kroll-Hess Hamiltonian and the appropriate basis of augmented valence quadruple ζ type. Coupled-cluster single, double, and perturbative triple calculations were performed for comparison.

High-speed THz spectroscopic imaging at ten kilohertz pixel rate with amplitude and phase contrast.

By combining the advantages of the high-speed ASOPS technology and efficient THz generation, we have realized a high-speed laser-based spectroscopic THz imaging system with more than 10,000 pixels per second acquisition speed and an excellent signal-to-noise ratio of more than 100. Unlike THz line cameras or mm-wave intensity detectors, the present device allows for a much higher spatial resolution and attributes each imaging pixel with phase and amplitude information up to several THz while simultaneously maintaining a very high scanning speed unmatched by any other technique presented so far. The high-speed acquisition allows for samples to be scanned even at sample velocities of 5 m/s or higher while preserving the fundamental resolution limit of the THz radiation, which is on the order of 500 µm in the present case.

Towards X-ray transient grating spectroscopy.

The extension of transient grating spectroscopy to the x-ray regime will create numerous opportunities, ranging from the study of thermal transport in the ballistic regime to charge, spin, and energy transfer processes with atomic spatial and femtosecond temporal resolution. Studies involving complicated split-and-delay lines have not yet been successful in achieving this goal. Here we propose a novel, simple method based on the Talbot effect for converging beams, which can easily be implemented at current x-ray free electron lasers. We validate our proposal by analyzing printed interference patterns on polymethyl methacrylate and gold samples using ∼3 keV X-ray pulses.

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9}) eV^{2}. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation.

[Metatarsal and toe fractures]. / Mittel- und Vorfußfrakturen.

Metatarsal and toe fractures are the most frequent injuries of the foot skeleton. Nondislocated fractures can be conservatively treated with good success. Long-term relief and immobilization including the ankle joint are unnecessary. Metatarsal fractures close to the base are nearly always associated with Lisfranc luxation and treatment must also take the instability of the tarsometatarsal joints into consideratíon. Basal fractures of the 5th metatarsal bone require a differentiated consideration. The correct classification is necessary in order to initiate an adequate treatment. In general, intra-articular layer formation, inclination >10° and shortening between 3 mm and 5 mm, taking the position of the head of the metatarsal bone into consideration, are recommended as indications for surgery. Operative treatment of toe fractures is only rarely necessary.

Instability of pulses in gradient reaction-diffusion systems: a symplectic approach.

In a scalar reaction-diffusion equation, it is known that the stability of a steady state can be determined from the Maslov index, a topological invariant that counts the state's critical points. In particular, this implies that pulse solutions are unstable. We extend this picture to pulses in reaction-diffusion systems with gradient nonlinearity. In particular, we associate a Maslov index to any asymptotically constant state, generalizing existing definitions of the Maslov index for homoclinic orbits. It is shown that this index equals the number of unstable eigenvalues for the linearized evolution equation. Finally, we use a symmetry argument to show that any pulse solution must have non-zero Maslov index, and hence be unstable.This article is part of the theme issue 'Stability of nonlinear waves and patterns and related topics'.

A review of the oral health-related quality of life (OHRQL) model for dental hygiene: Eighteen years later.

PURPOSE: The purpose of this paper is to review available evidence to determine the impact of the oral health-related quality of life (OHRQL) Model for Dental Hygiene on education, research, and practice. METHODS: A search was conducted in PubMed using the search terms oral health-related quality of life, OHRQL, and dental hygiene and limited to publications between 1998 and 2016. Google Scholar was also used to identify citations for the two original OHRQL model papers to capture the literature widely read by practicing dental hygienists but not indexed in PubMed. A total of 40 publications met the predetermined search strategy. Full publications were obtained and reviewed to determine how this research is being used in education, research, and practice. FINDINGS: The OHRQL is being utilized to a very limited degree in education, research, and practice. The literature shows how the OHRQL is actively being used in the school where the model originated in addition to a dental hygiene programme in Japan. Studies have been conducted on a variety of research instruments, including the OHRQL, designed to capture OHRQL outcomes. Japanese researchers have used the OHRQL in studies designed to determine the impact of oral healthcare delivery on patients' oral health-related quality of life. CONCLUSION: Eighteen years of the literature confirms that the OHRQL is being used minimally in education, research, and practice. Greater emphasis is needed around the collection and assessment of oral health-related quality of life measures for providing patient-centred care.

Increased risk of influenza among vaccinated adults who are obese.

BACKGROUND: Influenza infects 5-15% of the global population each year, and obesity has been shown to be an independent risk factor for increased influenza-related complications including hospitalization and death. However, the risk of developing influenza or influenza-like illness (ILI) in a vaccinated obese adult population has not been addressed. OBJECTIVE: This study evaluated whether obesity was associated with increased risk of influenza and ILI among vaccinated adults. SUBJECTS AND METHODS: During the 2013-2014 and 2014-2015 influenza seasons, we recruited 1042 subjects to a prospective observational study of trivalent inactivated influenza vaccine (IIV3) in adults. A total of 1022 subjects completed the study. Assessments of relative risk for laboratory confirmed influenza and ILI were determined based on body mass index. Seroconversion and seroprotection rates were determined using prevaccination and 26-35 days post vaccination serum samples. Recruitment criteria for this study were adults 18 years of age and older receiving the seasonal trivalent inactivated influenza vaccine (IIV3) for the years 2013-2014 and 2014-2015. Exclusion criteria were immunosuppressive diseases, use of immunomodulatory or immunosuppressive drugs, acute febrile illness, history of Guillain-Barre syndrome, use of theophylline preparations or use of warfarin. RESULTS: Among obese, 9.8% had either confirmed influenza or influenza-like-illness compared with 5.1% of healthy weight participants. Compared with vaccinated healthy weight, obese participants had double the risk of developing influenza or ILI (relative risk=2.01, 95% CI 1.12, 3.60, P=0.020). Seroconversion or seroprotection rates were not different between healthy weight and obese adults with influenza or ILI. CONCLUSIONS: Despite robust serological responses, vaccinated obese adults are twice as likely to develop influenza and ILI compared with healthy weight adults. This finding challenges the current standard for correlates of protection, suggesting use of antibody titers to determine vaccine effectiveness in an obese population may provide misleading information.

Mode stabilization in quantum cascade lasers via an intra-cavity cascaded nonlinearity.

We present self-stabilization of the inter-mode separation of a quantum cascade laser (QCL) emitting at 9 µm via cascaded second order nonlinearity. This effect has been observed in lasers that have the optical cavity embedded into a microwave strip-line. The intermodal beat note spectra narrow with increasing laser output power, up to less than 100 kHz. A flat frequency response to direct modulation up to 14 GHz is reported for these microstrip QCLs. The laser inter-mode spacing can be locked to an external RF signal and tuned by more than 1 MHz from the free-running spacing. A parallel study on the same laser material in a non-microstrip line waveguide shows superior performances of the microstrip QCL in terms of the intermodal spectral locking and stability. Finally by analyzing our results with the theory of the injection locking of coupled oscillators, we deduce that the microwave power injected in the microstrip QCL is 2 orders of magnitude higher than in the reference laser.

Rovibrational Characterization of High-Lying Electronic States of Cu2 by Double-Resonant Nonlinear Spectroscopy.

The available knowledge of the electronically excited states of the copper dimer is limited. This is common for transition metals, as the high density of states hinders both experimental assignment and computation. In this work, two-color resonant four-wave mixing spectroscopy was applied to neutral Cu2 in the gas phase. The method yielded accurate positions of individual rovibrational lines in the I-X and J-X electronic systems. This revealed the term symbols for the I and J states as 1Πu (1u) and 1Σu+ (0u+), respectively. For the 63Cu2 isotopologue, accurate molecular constants were obtained. The characterization of the J state finally allowed decisive determination of its electron configuration. The J state is obtained from the ground state by promotion of a 3dπg electron into the weakly bonding 4pπu molecular orbital. From the data analysis, lifetimes of the I state (between 10 ps and 5 ns) and J state (66 ns) were inferred.