Research inefficiencies in external validation studies of the Framingham Wilson coronary heart disease risk rule: A systematic review

Background: External validation studies create evidence about a clinical prediction rule’s (CPR’s) generalizability by evaluating and updating the CPR in populations different from those used in the derivation, and also by contributing to estimating its overall performance when meta-analysed in a systematic review. While most cardiovascular CPRs do not have any external validation, some CPRs have been externally validated repeatedly. Hence, we examined whether external validation studies of the Framingham Wilson coronary heart disease (CHD) risk rule contributed to generating evidence to their full potential. Methods: A forward citation search of the Framingham Wilson CHD risk rule’s derivation study was conducted to identify studies that evaluated the Framingham Wilson CHD risk rule in different populations. For external validation studies of the Framingham Wilson CHD risk rule, we examined whether authors updated the Framingham Wilson CHD risk rule when it performed poorly. We also assessed the contribution of external validation studies to understanding the Predicted/Observed (P/O) event ratio and c statistic of the Framingham Wilson CHD risk rule. Results: We identified 98 studies that evaluated the Framingham Wilson CHD risk rule; 40 of which were external validation studies. Of these 40 studies, 27 (67.5%) concluded the Framingham Wilson CHD risk rule performed poorly but did not update it. Of 23 external validation studies conducted with data that could be included in meta-analyses, 13 (56.5%) could not fully contribute to the meta-analyses of P/O ratio and/or c statistic because these performance measures were neither reported nor could be calculated from provided data. Discussion: Most external validation studies failed to generate evidence about the Framingham Wilson CHD risk rule’s generalizability to their full potential. Researchers might increase the value of external validation studies by presenting all relevant performance measures and by updating the CPR when it performs poorly

“Tinder Will Know You Are A 6”: Users’ Perceptions of Algorithms on Tinder

Through in-depth interviews of 22 Tinder users, we explore how users interpret their algorithmically mediated experience on the platform. We find that users have various explanations of whether and how Tinder uses algorithms and that users have varying degrees of certainty about these explanations. In response, users report that they act in particular ways given their explanations and degree of certainty. We discuss how users, as part of their sensemaking practice around how algorithms work, engage in forms of improvisation. In addition, we argue that algorithm awareness leads to a more nuanced acknowledgement of inequality and power, including the power-laden roles of platforms themselves

The Röt Halite Member of the Southern North Sea – a critical top seal for carbon dioxide storage in the Bunter Sandstone Formation

The Bunter Sandstone Formation is under consideration as a storage reservoir for carbon dioxide in the UK Southern North Sea, where the Dowsing Formation provides the top seal. Over much of the basin, an evaporitic unit known as the Röt Halite Member is present at the base of the Dowsing Formation. The Röt Halite is separated from the Bunter Sandstone by a thin mudstone unit equivalent to the Solling Formation of the Netherlands. Previous studies have suggested that the Röt Halite will provide an effective top seal for carbon dioxide storage on the basis that it is dominated by bedded halite (Heinemann et al., 2012; Williams et al., 2014). Despite this, detailed knowledge of the lithological heterogeneities and structural variations within the unit are lacking, specifically with respect to its potential to act as an effective seal for carbon dioxide. High-resolution correlation of petrophysical logs was conducted to provide an improved understanding of the distribution of individual halite cycles across the UK Southern North Sea. Seismic reflection data were then used to elicit information on post-depositional deformation styles, in an attempt to relate Röt Halite thickness and the number of individual cycles to the presence or absence of throughgoing faults

An analytical investigation into solute transport and sorption via intra-particle diffusion in the dual-porosity limit

We develop a mathematical model for adsorption based on averaging the flow around, and diffusion inside, adsorbent particles in a column. The model involves three coupled partial differential equations for the contaminant concentration both in the carrier fluid and within the particle as well as the adsorption rate. The adsorption rate is modelled using the Sips equation, which is suitable for describing both physical and chemical adsorption mechanisms. Non-dimensionalisation is used to determine the controlling parameter groups as well as to determine negligible terms and so reduce the system complexity. The inclusion of intra-particle diffusion introduces new dimensionless parameters to those found in standard works, including a form of internal Damk\"ohler number and a new characteristic time scale. We provide a numerical method for the full model and show how in certain situations a travelling wave approach can be utilized to find analytical solutions. The model is validated against available experimental data for the removal of Mercury(II) and CO$_\text{2}$. The results show excellent agreement with measurements of column outlet contaminant concentration and provide insights into the underlying chemical reactions.Comment: 36 pages, 10 figures, 8 table

How are maternal and fetal outcomes incorporated when measuring benefits of interventions in pregnancy? Findings from a systematic review of cost-utility analyses

Objective: Medical interventions used in pregnancy can affect the length and quality of life of both the pregnant person and fetus. The aim of this systematic review was to identify and describe the theoretical frameworks that underpin outcome measurement in cost-utility analyses of pregnancy interventions. Methods: Searches were conducted in the Paediatric Economic Database Evaluation (PEDE) database (up to 2017), as well as Medline, Embase and EconLit (2017–2019). We included all cost-utility analyses of any intervention given during pregnancy, published in English. We conducted a narrative synthesis of: study design; outcome construction (life expectancy, quality adjustment, discount rate); and whether the Incremental Cost-Effectiveness Ratio (ICER) was constructed using maternal or fetal outcomes. Where both outcomes were included, methods for combining them were extracted. Results: We identified 127 cost-utility analyses in pregnancy, of which 89 reported QALYs and 38 DALYs. Outcomes were considered solely for the fetus in 59 studies (47%), solely for the pregnant person in 13 studies (10%), and for both in 49 studies (39%). The choice to include or exclude one or both sets of outcomes was not consistent within particular clinical areas. Where outcomes for both mother and baby were included, methods for combining these outcomes varied. Twenty-nine studies summed QALYs/DALYs for maternal and fetal outcomes, with no adjustment. The remaining 20 took a variety of approaches designed to weigh maternal and fetal outcomes differently. These include (1) treating fetal outcomes as a component of maternal quality of life, rather than (or in addition to) an independent individual health outcome; (2) treating the maternal-fetal dyad as a single entity and applying a single utility value to each combination of outcomes; and (3) assigning a shorter time horizon to fetal outcomes to reduce the weight of lifetime fetal outcomes. Each approach made different assumptions about the relative value of maternal and fetal health outcomes, demonstrating a lack of consistency and the need for guidance. Conclusion: Methods for capturing QALY/DALY outcomes in cost-utility analysis in pregnancy vary widely. This lack of consistency indicates a need for new methods to support the valuation of maternal and fetal health outcomes

Presenting symptoms of cancer and stage at diagnosis: evidence from a cross-sectional, population-based study.

BACKGROUND: Early diagnosis interventions such as symptom awareness campaigns increasingly form part of global cancer control strategies. However, these strategies will have little impact in improving cancer outcomes if the targeted symptoms represent advanced stage of disease. Therefore, we aimed to examine associations between common presenting symptoms of cancer and stage at diagnosis. METHODS: In this cross-sectional study, we analysed population-level data from the English National Cancer Diagnosis Audit 2014 for patients aged 25 years and older with one of 12 types of solid tumours (bladder, breast, colon, endometrial, laryngeal, lung, melanoma, oral or oropharyngeal, ovarian, prostate, rectal, and renal cancer). We considered 20 common presenting symptoms and examined their associations with stage at diagnosis (TNM stage IV vs stage I-III) using logistic regression. For each symptom, we estimated these associations when reported as a single presenting symptom and when reported together with other symptoms. FINDINGS: We analysed data for 7997 patients. The proportion of patients diagnosed with stage IV cancer varied substantially by presenting symptom, from 1% (95% CI 1-3; eight of 584 patients) for abnormal mole to 80% (71-87; 84 of 105 patients) for neck lump. Three of the examined symptoms (neck lump, chest pain, and back pain) were consistently associated with increased odds of stage IV cancer, whether reported alone or with other symptoms, whereas the opposite was true for abnormal mole, breast lump, postmenopausal bleeding, and rectal bleeding. For 13 of the 20 symptoms (abnormal mole, breast lump, post-menopausal bleeding, rectal bleeding, lower urinary tract symptoms, haematuria, change in bowel habit, hoarseness, fatigue, abdominal pain, lower abdominal pain, weight loss, and the "any other symptom" category), more than 50% of patients were diagnosed at stages other than stage IV; for 19 of the 20 studied symptoms (all except for neck lump), more than a third of patients were diagnosed at stages other than stage IV. INTERPRETATION: Despite specific presenting symptoms being more strongly associated with advanced stage at diagnosis than others, for most symptoms, large proportions of patients are diagnosed at stages other than stage IV. These findings provide support for early diagnosis interventions targeting common cancer symptoms, countering concerns that they might be simply expediting the detection of advanced stage disease. FUNDING: UK Department of Health's Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis; and Cancer Research UK

TRAPHIC - Radiative Transfer for Smoothed Particle Hydrodynamics Simulations

We present TRAPHIC, a novel radiative transfer scheme for Smoothed Particle Hydrodynamics (SPH) simulations. TRAPHIC is designed for use in simulations exhibiting a wide dynamic range in physical length scales and containing a large number of light sources. It is adaptive both in space and in angle and can be employed for application on distributed memory machines. The commonly encountered computationally expensive scaling with the number of light sources in the simulation is avoided by introducing a source merging procedure. The (time-dependent) radiative transfer equation is solved by tracing individual photon packets in an explicitly photon-conserving manner directly on the unstructured grid traced out by the set of SPH particles. To accomplish directed transport of radiation despite the irregular spatial distribution of the SPH particles, photons are guided inside cones. We present and test a parallel numerical implementation of TRAPHIC in the SPH code GADGET-2, specified for the transport of mono-chromatic hydrogen-ionizing radiation. The results of the tests are in excellent agreement with both analytic solutions and results obtained with other state-of-the-art radiative transfer codes.Comment: 31 pages, 20 figures. Accepted for publication in MNRAS. Revised version includes many clarifications and a new time-dependent radiative transfer calculation (fig. 19

Improving convergence in smoothed particle hydrodynamics simulations without pairing instability

The numerical convergence of smoothed particle hydrodynamics (SPH) can be severely restricted by random force errors induced by particle disorder, especially in shear flows, which are ubiquitous in astrophysics. The increase in the number NH of neighbours when switching to more extended smoothing kernels at fixed resolution (using an appropriate definition for the SPH resolution scale) is insufficient to combat these errors. Consequently, trading resolution for better convergence is necessary, but for traditional smoothing kernels this option is limited by the pairing (or clumping) instability. Therefore, we investigate the suitability of the Wendland functions as smoothing kernels and compare them with the traditional B-splines. Linear stability analysis in three dimensions and test simulations demonstrate that the Wendland kernels avoid the pairing instability for all NH, despite having vanishing derivative at the origin (disproving traditional ideas about the origin of this instability; instead, we uncover a relation with the kernel Fourier transform and give an explanation in terms of the SPH density estimator). The Wendland kernels are computationally more convenient than the higher-order B-splines, allowing large NH and hence better numerical convergence (note that computational costs rise sub-linear with NH). Our analysis also shows that at low NH the quartic spline kernel with NH ~= 60 obtains much better convergence then the standard cubic spline.Comment: substantially revised version, accepted for publication in MNRAS, 15 pages, 13 figure