Precise QCD predictions for W-boson production in association with a charm jet.

The production of a W-boson with a charm quark jet provides a highly sensitive probe of the strange quark distribution in the proton. Employing a novel flavour dressing procedure to define charm quark jets, we compute W+charm-jet production up to next-to-next-to-leading order (NNLO) in QCD. We study the perturbative stability of production cross sections with same-sign and opposite-sign charge combinations for the W boson and the charm jet. A detailed breakdown according to different partonic initial states allows us to identify particularly suitable observables for the study of the quark parton distributions of different flavours.

Routine first-trimester pre-eclampsia screening and maternal left ventricular geometry.

OBJECTIVE: Pre-eclampsia (PE) is a pregnancy complication associated with premature cardiovascular disease morbidity and mortality (i.e. before 60 years of age or in the first year postpartum). PE is associated with adverse left ventricular (LV) remodeling in the peri- and postpartum periods, an independent risk factor for cardiovascular disease. This study aimed to compare LV geometry by LV mass (LVM) and LVM index (LVMI) between participants with a high vs low screening risk for preterm PE in the first trimester. METHODS: This was a prospective cohort study of singleton pregnancies between 11 + 0 and 13 + 6 weeks' gestation that underwent screening for preterm PE as part of their routine first-trimester ultrasound assessment at a tertiary center in London, UK, from February 2019 until March 2020. Screening for preterm PE was performed using the Fetal Medicine Foundation algorithm. Participants with a screening risk of ≥ 1 in 50 for preterm PE were classified as high risk and those with a screening risk of ≤ 1 in 500 were classified as low risk. All participants underwent two-dimensional and M-mode transthoracic echocardiography. RESULTS: A total of 128 participants in the first trimester of pregnancy were included in the analysis, with 57 (44.5%) participants screened as low risk and 71 (55.5%) participants as high risk for PE. The risk groups did not vary in maternal age and gestational age at assessment. Maternal body surface area and body mass index were significantly higher in the high-risk group (all P < 0.05). The high-risk participants were significantly more likely to be Afro-Caribbean, nulliparous and have a family history of hypertensive disease in pregnancy as well as other cardiovascular disease (all P < 0.05). In addition, mean arterial blood pressure (P < 0.001), mean heart rate (P < 0.001), median LVM (130.06 (interquartile range, 113.62-150.50) g vs 97.44 (81.68-114.16) g; P < 0.001) and mean LVMI (72.87 ± 12.2 g/m2 vs 57.54 ± 12.72 g/m2 ; P < 0.001) were significantly higher in the high-risk group. Consequently, those in the high-risk group were more likely to have abnormal LV geometry (37.1% vs 7.0%; P < 0.001). CONCLUSIONS: Early echocardiographic assessment in participants at high risk of preterm PE may unmask clinically healthy individuals who are at increased risk for future cardiovascular disease. Adverse cardiac remodeling in the first trimester of pregnancy may be an indicator of decreased cardiovascular reserve and subsequent dysfunctional cardiovascular adaptation in pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

NNLO QCD predictions for Z-boson production in association with a charm jet within the LHCb fiducial region.

We compute next-to-next-to-leading order (NNLO) QCD corrections to neutral vector boson production in association with a charm jet at the LHC. This process is studied in the forward kinematics at s = 13  TeV, which may provide valuable constraints on the intrinsic charm component of the proton. A comparison is performed between fixed order and NLO predictions matched to a parton shower showing mutual compatibility within the respective uncertainties. NNLO corrections typically lead to a reduction of theoretical uncertainties by a factor of two and the perturbative convergence is further improved through the introduction of a theory-inspired constraint on the transverse momentum of the vector boson plus jet system. A comparison between these predictions with data will require an alignment of a flavour-tagging procedure in theory and experiment that is infrared and collinear safe.

NNLO interpolation grids for jet production at the LHC.

Fast interpolation-grid frameworks facilitate an efficient and flexible evaluation of higher-order predictions for any choice of parton distribution functions or value of the strong coupling α s . They constitute an essential tool for the extraction of parton distribution functions and Standard Model parameters, as well as studies of the dependence of cross sections on the renormalisation and factorisation scales. The APPLfast project provides a generic interface between the parton-level Monte Carlo generator and both the APPLgrid and the fastNLO libraries for the grid interpolation. The extension of the project to include hadron-hadron collider processes at next-to-next-to-leading order in perturbative QCD is presented, together with an application for jet production at the LHC.

[Adaptation to changing needs in mental health care: mental health centers]. / Aanpassing aan veranderende zorgbehoefte in de ggz: mentale gezondheidscentra.

BACKGROUND: The increasing healthcare needs in the Netherlands lead to increasing healthcare costs and waiting lists and warrants sufficient (staff-)capacity. The current market-driven organization of care affects qualitative, accessible, and affordable care. Whether the Dutch mental healthcare system can adapt efficiently is questioned in this article. AIM: Gaining insight into the developments and bottlenecks that can contribute to the realization of appropriate care in mental health. METHOD: An overview of literature is given regarding developments and necessary adjustments in mental healthcare. RESULTS: Appropriate care is value-driven, focused on health (instead of the absence of illness), based on management of health of the client and his network, is accessible, affordable and is offered at the right time and place. The collaborative innovation of Mental Healthcare Centers, in which GGz Breburg (specialized mental health care), Indigo Brabant (general mental health care), and health insurance company, form a sustainable coalition which is presented as a solution for manageability of the mental healthcaresystem. This coalition aims to improve the public values of mental healthcare as a response to the required paradigm shift and future model of mental healthcare. CONCLUSION: As a regional network model, the Mental Healthcare Centers offer a desirable answer to the demand for an appropriate and future-proof mental healthcare. w.

Incidence of postpartum hypertension within 2 years of a pregnancy complicated by pre-eclampsia: a systematic review and meta-analysis.

BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased long-term risk of cardiovascular disease. However, there has been increasing evidence on the same risks in the months following birth. OBJECTIVES: This review aims to estimate the incidence of hypertension in the first 2 years after HDP. SEARCH STRATEGY: MEDLINE, Embase and Cochrane databases were systematically searched in October 2019. SELECTION CRITERIA: Observational studies comparing hypertension rate following HDP and normotensive pregnancies up to 2 years. DATA COLLECTION AND ANALYSIS: A meta-analysis to calculate the odds ratio (OR) with a 95% confidence interval (CI) and a sub-group analysis excluding women with chronic hypertension were performed. MAIN RESULTS: Hypertension was diagnosed within the first 2 years following pregnancy in 468/1646 (28.4%) and 584/6395 (9.1%) of the HDP and control groups, respectively (OR 6.28; 95% CI 4.18-9.43; I2  = 56%). The risk of hypertension in HDP group was significantly higher in the first 6 months following delivery (OR 18.33; 95% CI 1.35-249.48; I2  = 84%) than at 6-12 months (OR 4.36; 95% CI 2.81-6.76; I2  = 56%) or between 1-2 years postpartum (OR 7.24; 95% CI 4.44-11.80; I2  = 9%). A sub-group analysis demonstrated a similar increase in the risk of developing postpartum hypertension after HDP (OR 5.75; 95% CI 3.92-8.44; I2  = 49%) and pre-eclampsia (OR 6.83; 95% CI 4.25-10.96; I2  = 53%). CONCLUSIONS: The augmented risk of hypertension after HDP is highest in the early postpartum period, suggesting that diagnosis and targeted interventions to improve maternal cardiovascular health may need to be commenced in the immediate postpartum period. TWEETABLE ABSTRACT: The risk of hypertension within 2 years of birth is six-fold higher in women who experienced pre-eclampsia.

Predictions for Z-Boson Production in Association with a b-Jet at O(α_{s}

Precise predictions are provided for the production of a Z boson and a b-jet in hadron-hadron collisions within the framework of perturbative QCD, at O(α_{s}^{3}). To obtain these predictions, we perform the first calculation of a hadronic scattering process involving the direct production of a flavored jet at next-to-next-to-leading-order accuracy in massless QCD and extend techniques to also account for the impact of finite heavy-quark mass effects. The predictions are compared to CMS data obtained in pp collisions at a center-of-mass energy of 8 TeV, which are the most precise data from run I of the LHC for this process, where a good description of the data is achieved. To allow this comparison, we have performed an unfolding of the data, which overcomes the long-standing issue that the experimental and theoretical definitions of jet flavor are incompatible.

Calculations for deep inelastic scattering using fast interpolation grid techniques at NNLO in QCD and the extraction of α s from HERA data.

The extension of interpolation-grid frameworks for perturbative QCD calculations at next-to-next-to-leading order (NNLO) is presented for deep inelastic scattering (DIS) processes. A fast and flexible evaluation of higher-order predictions for any a posteriori choice of parton distribution functions (PDFs) or value of the strong coupling constant is essential in iterative fitting procedures to extract PDFs and Standard Model parameters as well as for a detailed study of the scale dependence. The APPLfast project, described here, provides a generic interface between the parton-level Monte Carlo program NNLOjet and both the APPLgrid and fastNLO libraries for the production of interpolation grids at NNLO accuracy. Details of the interface for DIS processes are presented together with the required interpolation grids at NNLO, which are made available. They cover numerous inclusive jet measurements by the H1 and ZEUS experiments at HERA. An extraction of the strong coupling constant is performed as an application of the use of such grids and a best-fit value of α s ( M Z ) = 0.1170 ( 15 ) exp ( 25 ) th is obtained using the HERA inclusive jet cross section data.

Triple Differential Dijet Cross Section at the LHC.

The measurement of the triple-differential dijet production cross section as a function of the average transverse momentum p_{T,avg}, half the rapidity separation y^{*}, and the boost y_{b} of the two leading jets in the event enables a kinematical scan of the underlying parton momentum distributions. We compute for the first time the second-order perturbative QCD corrections to this triple-differential dijet cross section, at leading color in all partonic channels, thereby enabling precision studies with LHC dijet data. A detailed comparison with experimental CMS 8 TeV data is performed, demonstrating how the shape of this differential cross section probes the parton densities in different kinematical ranges.

Vector boson production in association with a jet at forward rapidities.

Final states with a vector boson and a hadronic jet allow one to infer the Born-level kinematics of the underlying hard scattering process, thereby probing the partonic structure of the colliding protons. At forward rapidities, the parton collisions are highly asymmetric and resolve the parton distributions at very large or very small momentum fractions, where they are less well constrained by other processes. Using theory predictions accurate to next-to-next-to-leading order (NNLO) in QCD for both W ± and Z production in association with a jet at large rapidities at the LHC, we perform a detailed phenomenological analysis of recent LHC measurements. The increased theory precision allows us to clearly identify specific kinematical regions where the description of the data is insufficient. By constructing ratios and asymmetries of these cross sections, we aim to identify possible origins of the deviations, and highlight the potential impact of the data on improved determinations of parton distributions.

Next-to-Next-to-Leading-Order QCD Corrections to the Transverse Momentum Distribution of Weak Gauge Bosons.

The transverse momentum spectra of weak gauge bosons and their ratios probe the underlying dynamics and are crucial in testing our understanding of the standard model. They are an essential ingredient in precision measurements, such as the W boson mass extraction. To fully exploit the potential of the LHC data, we compute the second-order [next-to-next-to-leading-order (NNLO)] QCD corrections to the inclusive-p_{T}^{W} spectrum as well as to the ratios of spectra for W^{-}/W^{+} and Z/W. We find that the inclusion of NNLO QCD corrections considerably improves the theoretical description of the experimental CMS data and results in a substantial reduction of the residual scale uncertainties.

Precise Predictions for Dijet Production at the LHC.

We present the calculation of dijet production, doubly differential in dijet mass m_{jj} and rapidity difference |y^{*}|, at leading color in all partonic channels at next-to-next-to-leading order (NNLO) in perturbative QCD. We consider the long-standing problems associated with scale choice for dijet production at next-to-leading order (NLO) and investigate the impact of including the NNLO contribution. We find that the NNLO theory provides reliable predictions, even when using scale choices that display pathological behavior at NLO. We choose the dijet invariant mass as the theoretical scale on the grounds of perturbative convergence and residual scale variation and compare the predictions to the ATLAS 7 TeV 4.5 fb^{-1} data.

Precise predictions for V + jets dark matter backgrounds.

High-energy jets recoiling against missing transverse energy (MET) are powerful probes of dark matter at the LHC. Searches based on large MET signatures require a precise control of the Z ( ν ν ¯ ) +  jet background in the signal region. This can be achieved by taking accurate data in control regions dominated by Z ( ℓ + ℓ - ) +  jet, W ( ℓ ν ) +  jet and γ +  jet production, and extrapolating to the Z ( ν ν ¯ ) +  jet background by means of precise theoretical predictions. In this context, recent advances in perturbative calculations open the door to significant sensitivity improvements in dark matter searches. In this spirit, we present a combination of state-of-the-art calculations for all relevant V +  jets processes, including throughout NNLO QCD corrections and NLO electroweak corrections supplemented by Sudakov logarithms at two loops. Predictions at parton level are provided together with detailed recommendations for their usage in experimental analyses based on the reweighting of Monte Carlo samples. Particular attention is devoted to the estimate of theoretical uncertainties in the framework of dark matter searches, where subtle aspects such as correlations across different V +  jet processes play a key role. The anticipated theoretical uncertainty in the Z ( ν ν ¯ ) +  jet background is at the few percent level up to the TeV range.

Combination treatment with mirabegron and solifenacin in patients with overactive bladder: exploratory responder analyses of efficacy and evaluation of patient-reported outcomes from a randomized, double-blind, factorial, dose-ranging, Phase II study (SYMPHONY).

PURPOSE: This large dose-ranging study explored the benefits of different combinations of mirabegron and solifenacin on health-related quality of life (HRQoL), based on patient-reported outcomes (PROs), and patients ('responders') achieving clinically meaningful improvements in efficacy and HRQoL. METHODS: SYMPHONY (NCT01340027) was a Phase II, placebo- and monotherapy-controlled, dose-ranging, 12-week trial. Adult patients with overactive bladder (OAB) for ≥3 months were randomized to 1 of 12 groups: 6 combination (solifenacin 2.5/5/10 mg + mirabegron 25/50 mg), 5 monotherapy (solifenacin 2.5/5/10 mg, or mirabegron 25/50 mg), or placebo. Change from baseline to end of treatment was assessed, versus placebo and solifenacin 5 mg in: PROs (OAB-q [Symptom Bother/total HRQoL] and Patient Perception of Bladder Condition score), and responders achieving minimally important differences (MIDs) in PROs and predetermined clinically meaningful improvements in efficacy (e.g. <8 micturitions/24 h). Changes in PROs and responders were analysed using an ANCOVA model and logistic regression, respectively. RESULTS: The Full Analysis Set included 1278 patients. Combination therapy of solifenacin 5/10 mg + mirabegron 25/50 mg significantly improved PROs versus solifenacin 5 mg and placebo, and significantly more responders achieved MIDs in PROs and efficacy. Micturition frequency normalization was approximately twofold greater with 10 + 25 mg (OR 2.06 [95 % CI 1.11, 3.84; p = 0.023]) and 5 + 50 mg (OR 1.91 [95 % CI 1.14, 3.21; p = 0.015]) versus solifenacin 5 mg. CONCLUSION: Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg.

Impaired contrast sensitivity is associated with more severe cognitive impairment in Parkinson disease.

OBJECTIVES: Dopaminergic degeneration affects both nigrostriatal projection neurons and retinal amacrine cells in Parkinson disease (PD). Parkinsonian retinopathy is associated with impaired color discrimination and contrast sensitivity. Some prior studies described associations between color discrimination deficits and cognitive deficits in PD, suggesting that contrast discrimination deficits are due, at least in part, to cognitive deficits in PD. We investigated the relationship between cognitive deficits and impaired contrast sensitivity in PD. METHODS: PD subjects, n = 43; 15F/28M; mean age 66.5 ± 8.2, Hoehn and Yahr stage 2.6 ± 0.6, and duration of disease of 6.2 ± 5.0 years underwent neuropsychological and Rabin contrast sensitivity testing. RESULTS: Mean Rabin contrast sensitivity score was 1.34 ± 0.40. Bivariate analyses showed significant correlation between Rabin contrast sensitivity scores and global cognitive z-scores (R = 0.54, P = 0.0002). Cognitive domain Z-score post hoc analysis demonstrated most robust correlation between Rabin scores and executive functions (R = 0.49, P = 0.0009), followed by verbal learning (R = 0.44, P = 0.0028), visuospatial (R = 0.39, P = 0.001) and attention z-scores (R = 0.32, P = 0.036). CONCLUSIONS: Impaired contrast sensitivity in PD is robustly associated with cognitive deficits, particularly executive function deficits. These results suggest that contrast sensitivity may be a useful biomarker for cognitive changes in PD and may have implications for driving safety evaluations in PD.

Precise QCD Predictions for the Production of a Z Boson in Association with a Hadronic Jet.

We compute the cross section and differential distributions for the production of a Z boson in association with a hadronic jet to next-to-next-to-leading order (NNLO) in perturbative QCD, including the leptonic decay of the Z boson. We present numerical results for the transverse momentum and rapidity distributions of both the Z boson and the associated jet at the LHC. We find that the NNLO corrections increase the NLO predictions by approximately 1% and significantly reduce the scale variation uncertainty.

Patient and physician preferences for oral pharmacotherapy for overactive bladder: two discrete choice experiments.

OBJECTIVE: We examined patient and treating physician (general practitioners, urologists, and [uro]gynecologists) preferences for oral pharmacotherapy (antimuscarinics and beta-3 adrenoceptor agonists) for overactive bladder to gain a deeper understanding of which attributes drive their treatment decision-making and to quantify to what extent. RESEARCH DESIGN AND METHODS: Two separate discrete choice experiments were developed and validated using the input of patients and physicians. The patient experiment contained the following attributes: micturition frequency, incontinence, nocturia, urgency, dry mouth, constipation, increased heart rate, and increased blood pressure. The physician experiment contained two additional attributes: coping and atrial fibrillation. Both were fielded in five European countries. To allow for preference heterogeneity, utility functions were estimated using a mixed multinomial logit model. RESULTS: A total of 442 patient and 318 physician responses were analyzed. Patients ranked the attributes based on their largest potential impact on treatment value as follows: incontinence, nocturia, risk of an increased heart rate, urgency, frequency, risk of increased blood pressure, risk of constipation, and risk of dry mouth; and physicians as follows: incontinence, urgency, nocturia, frequency, risk of dry mouth, coping, risk of increased heart rate, risk of increased blood pressure, risk of atrial fibrillation, and risk of constipation. CONCLUSION AND LIMITATIONS: In their valuations, physicians put more emphasis on increasing benefits, whereas patients put more emphasis on limiting risks of side effects. Another contrast that emerged was that patients' valuations of side effects were found to be fairly insensitive to the presented risk levels (with the exception of risk of dry mouth), whereas physicians' evaluated all side effects in a risk-level dependent manner. The obtained utility functions can be used to predict whether, to what extent, and for which reasons patients and physicians would choose one oral pharmacotherapy over another, as well as to advance shared decision-making.

A quantitative benefit-risk assessment approach to improve decision making in drug development: Application of a multicriteria decision analysis model in the development of combination therapy for overactive bladder.

A multicriteria decision analysis (MCDA) approach was developed and used to estimate the benefit-risk of solifenacin and mirabegron and their combination in the treatment of overactive bladder (OAB). The objectives were 1) to develop an MCDA tool to compare drug effects in OAB quantitatively, 2) to establish transparency in the evaluation of the benefit-risk profile of various dose combinations, and 3) to quantify the added value of combination use compared to monotherapies. The MCDA model was developed using efficacy, safety, and tolerability attributes and the results of a phase II factorial design combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron 25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and supported combination therapy development of solifenacin and mirabegron for phase III clinical development at these dose regimens. This case study underlines the benefit of using a quantitative approach in clinical drug development programs.

The analysis of incontinence episodes and other count data in patients with overactive bladder by Poisson and negative binomial regression.

Clinical studies in overactive bladder have traditionally used analysis of covariance or nonparametric methods to analyse the number of incontinence episodes and other count data. It is known that if the underlying distributional assumptions of a particular parametric method do not hold, an alternative parametric method may be more efficient than a nonparametric one, which makes no assumptions regarding the underlying distribution of the data. Therefore, there are advantages in using methods based on the Poisson distribution or extensions of that method, which incorporate specific features that provide a modelling framework for count data. One challenge with count data is overdispersion, but methods are available that can account for this through the introduction of random effect terms in the modelling, and it is this modelling framework that leads to the negative binomial distribution. These models can also provide clinicians with a clearer and more appropriate interpretation of treatment effects in terms of rate ratios. In this paper, the previously used parametric and non-parametric approaches are contrasted with those based on Poisson regression and various extensions in trials evaluating solifenacin and mirabegron in patients with overactive bladder. In these applications, negative binomial models are seen to fit the data well.