A temperate Earth-sized planet with tidal heating transiting an M6 star.

Temperate Earth-sized exoplanets around late-M dwarfs offer a rare opportunity to explore under which conditions planets can develop hospitable climate conditions. The small stellar radius amplifies the atmospheric transit signature, making even compact secondary atmospheres dominated by N2 or CO2 amenable to characterization with existing instrumentation1. Yet, despite large planet search efforts2, detection of low-temperature Earth-sized planets around late-M dwarfs has remained rare and the TRAPPIST-1 system, a resonance chain of rocky planets with seemingly identical compositions, has not yet shown any evidence of volatiles in the system3. Here we report the discovery of a temperate Earth-sized planet orbiting the cool M6 dwarf LP 791-18. The newly discovered planet, LP 791-18d, has a radius of 1.03 ± 0.04 R⊕ and an equilibrium temperature of 300-400 K, with the permanent night side plausibly allowing for water condensation. LP 791-18d is part of a coplanar system4 and provides a so-far unique opportunity to investigate a temperate exo-Earth in a system with a sub-Neptune that retained its gas or volatile envelope. On the basis of observations of transit timing variations, we find a mass of 7.1 ± 0.7 M⊕ for the sub-Neptune LP 791-18c and a mass of [Formula: see text] for the exo-Earth LP 791-18d. The gravitational interaction with the sub-Neptune prevents the complete circularization of LP 791-18d's orbit, resulting in continued tidal heating of LP 791-18d's interior and probably strong volcanic activity at the surface5,6.

Early Release Science of the exoplanet WASP-39b with JWST NIRSpec G395H.

Measuring the abundances of carbon and oxygen in exoplanet atmospheres is considered a crucial avenue for unlocking the formation and evolution of exoplanetary systems1,2. Access to the chemical inventory of an exoplanet requires high-precision observations, often inferred from individual molecular detections with low-resolution space-based3-5 and high-resolution ground-based6-8 facilities. Here we report the medium-resolution (R ≈ 600) transmission spectrum of an exoplanet atmosphere between 3 and 5 µm covering several absorption features for the Saturn-mass exoplanet WASP-39b (ref. 9), obtained with the Near Infrared Spectrograph (NIRSpec) G395H grating of JWST. Our observations achieve 1.46 times photon precision, providing an average transit depth uncertainty of 221 ppm per spectroscopic bin, and present minimal impacts from systematic effects. We detect significant absorption from CO2 (28.5σ) and H2O (21.5σ), and identify SO2 as the source of absorption at 4.1 µm (4.8σ). Best-fit atmospheric models range between 3 and 10 times solar metallicity, with sub-solar to solar C/O ratios. These results, including the detection of SO2, underscore the importance of characterizing the chemistry in exoplanet atmospheres and showcase NIRSpec G395H as an excellent mode for time-series observations over this critical wavelength range10.

Targeted prophylactic anticoagulation based on the TRiP(cast) score in patients with lower limb immobilisation: a multicentre, stepped wedge, randomised implementation trial.

BACKGROUND: Prophylactic anticoagulation in emergency department patients with lower limb trauma requiring immobilisation is controversial. The Thrombosis Risk Prediction for Patients with Cast Immobilisation-TRiP(cast)-score could identify a large subgroup of patients at low risk of venous thromboembolism for whom prophylactic anticoagulation can be safely withheld. We aimed to prospectively assess the safety of withholding anticoagulation for patients with lower limb trauma at low risk of venous thromboembolism, defined by a TRiP(cast) score of less than 7. METHODS: CASTING was a stepped-wedge, multicentre, cluster-randomised trial with blinded outcome assessment. 15 emergency departments in France and Belgium were selected and randomly assigned staggered start dates for switching from the control phase (ie, anticoagulation prescription according to the physician's usual practice) to the intervention phase (ie, targeted anticoagulation according to TRiP(cast) score: no prescription if score <7 and anticoagulation if score was ≥7). Patients were included if they presented to a participating emergency department with lower limb trauma requiring immobilisation for at least 7 days and were aged 18 years or older. The primary outcome was the 3-month cumulative rate of symptomatic venous thromboembolism during the intervention phase in patients with a TRiP(cast) score of less than 7. The targeted strategy was considered safe if this rate was less than 1% with an upper 95% CI of less than 2%. The primary analysis was performed in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT04064489). FINDINGS: Between June 16, 2020, and Sept 15, 2021, 15 clusters and 2120 patients were included. Of the 1505 patients analysed in the intervention phase, 1159 (77·0%) had a TRiP(cast) score of less than 7 and did not receive anticoagulant treatment. The symptomatic venous thromboembolism rate was 0·7% (95% CI 0·3-1·4, n=8/1159). There was no difference between the control and the intervention phases in the cumulative rate of symptomatic venous thromboembolism or in bleeding rates. INTERPRETATION: Patients with a TRiP(cast) score of less than 7 who are not receiving anticoagulation have a very low risk of venous thromboembolism. A large proportion of patients with lower limb trauma and immobilisation could safely avoid thromboprophylaxis. FUNDING: French Ministry of Health.

Operator Formulation of Feynman Path Centroid Dynamics for Rotations.

An operator formulation of centroid molecular dynamics (CMD) for rotational degrees of freedom is presented. The quasi-density operator concept was introduced by Jang and Voth [J. Chem. Phys 111, 2357 (1999)] and is used to obtain a phase-space mapping without the need for discretized path integrals. The approach allows the calculation of approximate Kubo-transformed time correlation functions. The particle on a ring is chosen as an illustrative example. Numerical results demonstrate that the proposed approach leads to accurate results when compared with exact diagonalization calculations for linear operators. At very low temperatures, it is found that rotational CMD yields results that are in exact agreement with the quantum dynamics of a spin-1 system.

A neural network-based four-body potential energy surface for parahydrogen.

We present an isotropic ab initio (para-H2)4 four-body interaction potential energy surface (PES). The electronic structure calculations are performed at the correlated coupled-cluster theory level, with single, double, and perturbative triple excitations. They use an atom-centered augmented correlation-consistent double zeta basis set, supplemented by a (3s3p2d) midbond function. We use a multilayer perceptron to construct the PES. We apply a rescaling transformation to the output energies during training to improve the prediction of weaker energies in the sample data. At long distances, the interaction energies are adjusted to match the empirically derived four-body dispersion interaction. The four-body interaction energy at short intermolecular separations is net repulsive. The use of this four-body PES, in combination with a first principles pair potential for para-H2 [J. Chem. Phys. 119, 12551 (2015)] and an isotropic ab initio three-body potential for para-H2 [J. Chem. Phys. 156, 044301 (2022)], is expected to provide closer agreement with experimental results.

Ground states of planar dipolar rotor chains with recurrent neural networks.

In this contribution, we employ a recurrent neural network (RNN) architecture in a variational optimization to obtain the ground state of linear chains of planar, dipolar rotors. We test different local basis sets and discuss their impact on the sign structure of the many-body ground state wavefunction. It is demonstrated that the RNN ansatz we employ is able to treat systems with and without a sign problem in the ground state. For larger chains with up to 50 rotors, accurate properties, such as correlation functions and Binder parameters, are calculated. By employing quantum annealing, we show that precise entanglement properties can be obtained. All these properties allow one to identify a quantum phase transition between a paraelectric and a ferroelectric quantum phase.

Quantum criticality in chains of planar rotors with dipolar interactions.

In this work, we perform a density matrix renormalization group study of chains of planar rotors interacting via dipolar interactions. By exploring the ground state from weakly to strongly interacting rotors, we find the occurrence of a quantum phase transition between a disordered and a dipole-ordered quantum state. We show that the nature of the ordered state changes from ferroelectric to antiferroelectric when the relative orientation of the rotor planes varies and that this change requires no modification of the overall symmetry. The observed quantum phase transitions are characterized by critical exponents and central charges, which reveal different universality classes ranging from that of the (1 + 1)D Ising model to the 2D classical XY model.

Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial.

Rationale: Management of first episodes of primary spontaneous pneumothorax remains the subject of debate. Objectives: To determine whether first-line simple aspiration is noninferior to first-line chest tube drainage for lung expansion in patients with complete primary spontaneous pneumothorax. Methods: We conducted a prospective, open-label, randomized noninferiority trial. Adults aged 18-50 years with complete primary spontaneous pneumothorax (total separation of the lung from the chest wall), recruited at 31 French hospitals from 2009 to 2015, received simple aspiration (n = 200) or chest tube drainage (n = 202) as first-line treatment. The primary outcome was pulmonary expansion 24 hours after the procedure. Secondary outcomes were tolerance of treatment, occurrence of adverse events, and recurrence of pneumothorax within 1 year. Substantial discordance in the numerical inputs used for trial planning and the actual trial rates of the primary outcome resulted in a reevaluation of the trial analysis plan. Measurement and Main Results: Treatment failure occurred in 29% in the aspiration group and 18% in the chest tube drainage group (difference in failure rate, 0.113; 95% confidence interval [CI], 0.026-0.200). The aspiration group experienced less pain overall (mean difference, -1.4; 95% CI, -1.89, -0.91), less pain limiting breathing (frequency difference, -0.18; 95% CI, -0.27, -0.09), and less kinking of the device (frequency difference, -0.05; 95% CI, -0.09, -0.01). Recurrence of pneumothorax was 20% in this group versus 27% in the drainage group (frequency difference, -0.07; 95% CI, -0.16, +0.02). Conclusions: First-line management of complete primary spontaneous pneumothorax with simple aspiration had a higher failure rate than chest tube drainage but was better tolerated with fewer adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT01008228).

Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis.

AIMS: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. METHODS AND RESULTS: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). CONCLUSION: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. REGISTRATION: PROSPERO ID 89366.

Derivation and validation of a risk-stratification model for patients with probable or proven COVID-19 in EDs: the revised HOME-CoV score.

BACKGROUND: The HOME-CoV (Hospitalisation or Outpatient ManagEment of patients with SARS-CoV-2 infection) score is a validated list of uniquely clinical criteria indicating which patients with probable or proven COVID-19 can be treated at home. The aim of this study was to optimise the score to improve its ability to discriminate between patients who do and do not need admission. METHODS: A revised HOME-CoV score was derived using data from a previous prospective multicentre study which evaluated the original Home-CoV score. Patients with proven or probable COVID-19 attending 34 EDs in France, Monaco and Belgium between April and May 2020 were included. The population was split into a derivation and validation sample corresponding to the observational and interventional phases of the original study. The main outcome was non-invasive or invasive ventilation or all-cause death within 7 days following inclusion. Two threshold values were defined using a sensitivity of >0.9 and a specificity of >0.9 to identify low-risk and high-risk patients, respectively. The revised HOME-CoV score was then validated by retrospectively applying it to patients in the same EDs with proven or probable COVID-19 during the interventional phase. The revised HOME-CoV score was also tested against original HOME-CoV, qCSI, qSOFA, CRB65 and SMART-COP in this validation cohort. RESULTS: There were 1696 patients in the derivation cohort, of whom 65 (3.8%) required non-invasive ventilation or mechanical ventilation or died within 7 days and 1304 patients in the validation cohort, of whom 22 (1.7%) had a progression of illness. The revised score included seven clinical criteria. The area under the curve (AUC) was 87.6 (95% CI 84.7 to 90.6). The cut-offs to define low-risk and high-risk patients were <2 and >3, respectively. In the validation cohort, the AUC was 85.8 (95% CI 80.6 to 91.0). A score of <2 qualified 73% of patients as low risk with a sensitivity of 0.77 (0.55-0.92) and a negative predictive value of 0.99 (0.99-1.00). CONCLUSION: The revised HOME-CoV score, which does not require laboratory testing, may allow accurate risk stratification and safely qualify a significant proportion of patients with probable or proven COVID-19 for home treatment.

Generating Exchange-Correlation Functionals with a Simplified, Self-Consistent Correlation Factor Model.

We focus on the spherically averaged exchange-correlation hole ρXC(r, u) of density functional theory, which describes the reduction in the electron density at a distance u due to the reference electron localized at position r. The correlation factor (CF) approach, where the model exchange hole ρXmodel(r, u) is multiplied by a CF (fC(r, u)) to yield an approximation to the exchange-correlation hole ρXC(r, u) = fC(r, u) ρXmodel(r, u), has proven to be a powerful tool for the development of new approximations. One of the remaining challenges within the CF approach is the self-consistent implementation of the resulting functionals. To address this issue, here we propose a simplification of the previously developed CFs such that self-consistent implementations become feasible. As an illustration of the simplified CF model, we develop a new meta-GGA functional, and using only a minimum of empiricism, we provide an easy derivation of an approximation that is of an accuracy similar to more involved meta-GGA functionals.

Optimized basis sets for DMRG calculations of quantum chains of rotating water molecules.

In this contribution, we employ a density matrix-based optimization procedure to obtain customized basis functions to describe chains of rotating water molecules in interaction regimes associated with different intermolecular distances. This procedure is shown to yield a very compact basis with a clear truncation criterion based on the population of the single particle basis functions. For the water trimer, we discuss the convergence behavior of several properties and show it to be superior when compared to an energy-based truncated basis. It is demonstrated that the optimized basis reduces the necessary number of basis functions by at least an order of magnitude. Finally, the optimization procedure is employed to study larger chains of up to ten water molecules. The formation of hydrogen bonds as well as its impact on the net polarization of the chain is discussed.

The electron-centric approach to the exchange-correlation energy.

The Kohn-Sham theory addresses the challenge of representing the kinetic energy by re-quantizing density functional theory at a level of non-interacting electrons. It transforms the many-electron problem into a fictitious non-interacting electron problem, with the many-electron effects concealed within the exchange-correlation (XC) energy, which is expressed in terms of the electron density ρ(r). Unlike the wave function, ρ(r) can be viewed as a classical quantity, and expressing the XC energy in terms of it circumvents the need for correlated wave functions. In this work, we once again employ the re-quantization strategy and determine the XC energy using a local one-particle Schrödinger equation. The ground-state eigenfunction of the corresponding Hamiltonian is a reference point (r) dependent orbital φr,σ(u, σ') which is subsequently used to generate the XC hole and the XC energy. The spin coordinate is denoted by σ and u is the electron-electron separation. The one-particle equation for φr,σ(u, σ') includes a local potential vr,σ(u, σ') that we approximate using two simple physical constraints. We assess the approximation by applying it to the helium iso-electronic series, the homogeneous electron gas, and the dissociation of the hydrogen molecule.

On the nature of the Schottky anomaly in endohedral water.

In this work, we study the heat capacity contribution of a rigid water molecule encapsulated in C60 by performing six-dimensional eigenstate calculations with the inclusion of its quantized rotational and translational degrees of freedom. Two confinement model potentials are considered: in the first, confinement is described using distributed pairwise Lennard-Jones interactions, while in the second, the water molecule is trapped within an eccentric but isotropic 3D harmonic effective confinement potential [Wespiser et al., J. Chem. Phys. 156, 074304 (2022)]. Contributions to the heat capacity from both the ortho and para nuclear spin isomers of water are considered to enable the effects of their interconversion to be assessed. By including a symmetry-breaking quadrupolar potential energy term in the Hamiltonian, we can reproduce the experimentally observed Schottky anomaly at ∼2 K [Suzuki et al., J. Phys. Chem. Lett. 10, 1306 (2019)]. Furthermore, our calculations predict a second Schottky anomaly at ∼0.1 K resulting from the H configuration, a different orientational arrangement of the fullerene cages in crystalline solid C60. Contributions from the H configuration to CV also explain the second peak observed at ∼7 K in the experimentally measured heat capacity.

Risk for Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation : A Multicenter Prospective Cohort Study.

BACKGROUND: The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, suggesting a lesser severity of illness. The clinical importance of patients with pulmonary embolism isolated to the subsegmental vessels is unknown. OBJECTIVE: To determine the rate of recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation. DESIGN: Multicenter prospective cohort study. (ClinicalTrials.gov: NCT01455818). SETTING: Eighteen sites between February 2011 and February 2021. PATIENTS: Patients with isolated subsegmental pulmonary embolism. INTERVENTION: At diagnosis, patients underwent bilateral lower-extremity venous ultrasonography, which was repeated 1 week later if results were negative. Patients without deep venous thrombosis did not receive anticoagulant therapy. MEASUREMENTS: The primary outcome was recurrent venous thromboembolism during the 90-day follow-up period. RESULTS: Recruitment was stopped prematurely because the predefined stopping rule was met after 292 of a projected 300 patients were enrolled. Of the 266 patients included in the primary analysis, the primary outcome occurred in 8 patients, for a cumulative incidence of 3.1% (95% CI, 1.6% to 6.1%) over the 90-day follow-up. The incidence of recurrent venous thromboembolism was 2.1% (CI, 0.8% to 5.5%) and 5.7% (CI, 2.2% to 14.4%) over the 90-day follow-up in patients with single and multiple isolated subsegmental pulmonary embolism, respectively. No patients had a fatal recurrent pulmonary embolism. LIMITATION: The study was restricted to patients with low-risk subsegmental pulmonary embolism. CONCLUSION: Overall, patients with subsegmental pulmonary embolism who did not have proximal deep venous thrombosis had a higher-than-expected rate of recurrent venous thromboembolism. PRIMARY FUNDING SOURCE: Heart and Stroke Foundation of Canada and French Ministry of Health Programme Hospitalier de Recherche Clinique.

Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic Review and Individual-Patient Data Meta-analysis.

BACKGROUND: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. PURPOSE: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. DATA SOURCES: MEDLINE from 1 January 1995 until 1 January 2021. STUDY SELECTION: 16 studies assessing at least 1 diagnostic strategy. DATA EXTRACTION: Individual-patient data from 20 553 patients. DATA SYNTHESIS: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. LIMITATIONS: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. CONCLUSION: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. PRIMARY FUNDING SOURCE: Dutch Research Council. (PROSPERO: CRD42018089366).

Management of epistaxis associated with oral antithrombotic drugs in emergency department and impact on prescription thereafter.

OBJECTIVES: To describe management, and to assess factors associated with antithrombotic prescription thereafter in patients who had epistaxis referred to emergency department (ED). DESIGN: Prospective cohort study. From EDs, clinical, biological and hospital data were collected. The clinical database was linked to the French Health Insurance Database where we retrieved antithrombotic drug deliveries in a 3-month period before and after referral. SETTING: Multicentric population-based cohort study within five well-defined areas. PARTICIPANTS: We considered 306 patients referred for epistaxis with a stable oral antithrombotic regimen before referral. MAIN OUTCOME MEASURES: We considered management, hospital outcome and case fatality. Antithrombotic prescription in a 3-month follow-up period was categorised into three classes: no change, class change, or discontinuation. During follow-up, hospitalisation for epistaxis or ischaemic events was searched. RESULTS: Among 306 adult individuals (mean age: 76 years), 166 took oral anticoagulant and 140 an antiplatelet drug. Blood transfusion was needed in 13.7% of patients and anterior packing alone in 61%. Half of the patients were hospitalised; 301 were discharged alive. Considering antithrombotic prescription thereafter we observed no change in 219 patients (72.8%), class changes in 47 patients (15.6%) and discontinuation in 35 patients (11.6%). We identified four independent predictors for antithrombotic prescription: hospitalisation (vs. returning home, p = .05), age (p = .03), haemoglobin level (p = .03) and oral anticoagulant (vs. antiplatelet agent, p < .001). During the 3 months following discharge, 2 thrombotic and 15 bleeding events were identified. CONCLUSIONS: Epistaxis referred to emergency department had an impact on subsequent antithrombotic prescription. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02886533.

Ruling out pulmonary embolism across different healthcare settings: A systematic review and individual patient data meta-analysis.

BACKGROUND: The challenging clinical dilemma of detecting pulmonary embolism (PE) in suspected patients is encountered in a variety of healthcare settings. We hypothesized that the optimal diagnostic approach to detect these patients in terms of safety and efficiency depends on underlying PE prevalence, case mix, and physician experience, overall reflected by the type of setting where patients are initially assessed. The objective of this study was to assess the capability of ruling out PE by available diagnostic strategies across all possible settings. METHODS AND FINDINGS: We performed a literature search (MEDLINE) followed by an individual patient data (IPD) meta-analysis (MA; 23 studies), including patients from self-referral emergency care (n = 12,612), primary healthcare clinics (n = 3,174), referred secondary care (n = 17,052), and hospitalized or nursing home patients (n = 2,410). Multilevel logistic regression was performed to evaluate diagnostic performance of the Wells and revised Geneva rules, both using fixed and adapted D-dimer thresholds to age or pretest probability (PTP), for the YEARS algorithm and for the Pulmonary Embolism Rule-out Criteria (PERC). All strategies were tested separately in each healthcare setting. Following studies done in this field, the primary diagnostic metrices estimated from the models were the "failure rate" of each strategy-i.e., the proportion of missed PE among patients categorized as "PE excluded" and "efficiency"-defined as the proportion of patients categorized as "PE excluded" among all patients. In self-referral emergency care, the PERC algorithm excludes PE in 21% of suspected patients at a failure rate of 1.12% (95% confidence interval [CI] 0.74 to 1.70), whereas this increases to 6.01% (4.09 to 8.75) in referred patients to secondary care at an efficiency of 10%. In patients from primary healthcare and those referred to secondary care, strategies adjusting D-dimer to PTP are the most efficient (range: 43% to 62%) at a failure rate ranging between 0.25% and 3.06%, with higher failure rates observed in patients referred to secondary care. For this latter setting, strategies adjusting D-dimer to age are associated with a lower failure rate ranging between 0.65% and 0.81%, yet are also less efficient (range: 33% and 35%). For all strategies, failure rates are highest in hospitalized or nursing home patients, ranging between 1.68% and 5.13%, at an efficiency ranging between 15% and 30%. The main limitation of the primary analyses was that the diagnostic performance of each strategy was compared in different sets of studies since the availability of items used in each diagnostic strategy differed across included studies; however, sensitivity analyses suggested that the findings were robust. CONCLUSIONS: The capability of safely and efficiently ruling out PE of available diagnostic strategies differs for different healthcare settings. The findings of this IPD MA help in determining the optimum diagnostic strategies for ruling out PE per healthcare setting, balancing the trade-off between failure rate and efficiency of each strategy.

Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism.

BACKGROUND: Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with suspected pulmonary embolism undergo computed tomographic (CT) pulmonary angiography or ventilation-perfusion scanning, both of which involve radiation exposure to the mother and fetus. Whether a pregnancy-adapted algorithm could be used to safely avoid diagnostic imaging in pregnant women with suspected pulmonary embolism is unknown. METHODS: In a prospective study involving pregnant women with suspected pulmonary embolism, we assessed three criteria from the YEARS algorithm (clinical signs of deep-vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the d-dimer level. Pulmonary embolism was ruled out if none of the three criteria were met and the d-dimer level was less than 1000 ng per milliliter or if one or more of the three criteria were met and the d-dimer level was less than 500 ng per milliliter. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep-vein thrombosis; if the results were positive (i.e., a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism. RESULTS: A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep-vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval [CI], 0.04 to 1.2); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% CI, 35 to 44). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester. CONCLUSIONS: Pulmonary embolism was safely ruled out by the pregnancy-adapted YEARS diagnostic algorithm across all trimesters of pregnancy. CT pulmonary angiography was avoided in 32 to 65% of patients. (Funded by Leiden University Medical Center and 17 other participating hospitals; Artemis Netherlands Trial Register number, NL5726.).

ROESY and 13C NMR to distinguish between D- and L-rhamnose in the α-D-Manp-(1 → 4)-ß-Rhap-(1 → 3) repeating motif.

Many children suffering from autism spectrum disorder (ASD) experience gastrointestinal (GI) conditions. Enterocloster bolteae has been regularly detected in the stool of individuals suffering from GI symptoms and autism. Literature has suggested that E. bolteae strains WAL 16351 and WAL 14578 produce an immunogenic capsular polysaccharide (CPS) comprised of disaccharide repeating units: α-D-Man-(1 → 4)-ß-Rha-(1 → 3) that could be used for the development of an immunotherapeutic vaccine. Ambiguity in the configuration of rhamnose led to the synthesis of tri- and disaccharide analogues containing D-rhamnose and L-rhamnose, respectively. ROESY-NMR spectra showed that CH3-6 of rhamnose and H-2 of mannose in the L-Rha containing disaccharide gave correlation. No such correlation was seen between the CH3-6 of rhamnose and the H-2 of mannose in the D-Rha containing trisaccharide. Molecular dynamics studies on hexasaccharide containing L-Rha or D-Rha confirmed that these structures adopt conformations resulting in different distances between the C6-rhamnose and the H-2 mannose of the preceding residue. We also demonstrate that assignment of the absolute configuration of the rhamnosyl residue in the ß-Rhap-(1 → 3)-D-Man linkage can be determined using the 13C chemical shift of C-2 in of D-Mannose. While ß-D-Rha will lead to an upfield shift of C-2 due to γ-gauche interaction between H-1 Rha and H-2 Man, ß-L-Rha will not. Our results provide insights to distinguish between D- and L-rhamnose in the α-D-Manp-(1 → 4)-ß-Rhap-(1 → 3) repeating motif.