Recovery of the breast screening programme following pandemic-related delays: Should we focus on round length or uptake?

OBJECTIVES: The NHS Breast Screening programme is recovering from the hiatus in screening in 2020 due to the COVID-19 pandemic. Currently, open rather than timed invitations are issued, which leads to lower uptake but more rapid coverage of the eligible population by invitation and therefore closer adherence to a round length of 3 years. We aimed to estimate the likely effect on numbers of cancers detected at incident screens of a range of round lengths and uptake rates. METHODS: We assumed exponential distributions of time to incidence of preclinical screen-detectable cancer and of time to progression thereafter to symptomatic clinical disease. We derived numerical values of these, along with screening sensitivity, from published research results and statistics from the NHS Breast Screening programme. These were used to calculate numbers of cancers detected at incident screens at ages 51–70 by round length and uptake rates. RESULTS: We found that in a homogeneous population of cancers, a 4-year round length with uptake of 62%, as observed with timed appointments in London before the pandemic, would result in 295 cancers screen detected per 10,000 invited, compared to 222 cancers with a 3-year round and uptake of 46%, as observed in London during the recovery period. Similar results were found when we posited two populations, one of rapidly progressing and one of slowly progressing cancers. CONCLUSIONS: It may be more productive in terms of early detection to focus on uptake rather than round length in the programme's recovery from the pandemic

Information Ambiguity, Market Institutions and Asset Prices: Experimental Evidence

We explore how information ambiguity and traders’ attitudes toward such ambiguity affect expectations and asset prices under three different market institutions. Specifically, we test the prediction of Epstein & Schneider (2008) that information ambiguity will lead market prices to overreact to bad news and to underreact to good news. We find that such an asymmetric reaction exists and is strongest in individual prediction markets. It occurs to a lesser extent in single price call markets. It is weakest of all in double auction markets, where buyers’ asymmetric reaction to good/bad news is cancelled out by the opposite asymmetric reaction of sellers

Carrier density crossover and quasiparticle mass enhancement in a doped 5dd Mott insulator

High-temperature superconductivity in cuprates emerges upon doping the parent Mott insulator. Robust signatures of the low-doped electronic state include a Hall carrier density that initially tracks the number of doped holes and the emergence of an anisotropic pseudogap; the latter characterised by disconnected Fermi arcs, closure at a critical doping level $p^* \approx 0.19$, and, in some cases, a strongly enhanced carrier effective mass. In Sr$_2$IrO$_4$, a spin-orbit-coupled Mott insulator often regarded as a 5$d$ analogue of the cuprates, surface probes have revealed the emergence of an anisotropic pseudogap and Fermi arcs under electron doping, though neither the corresponding $p^*$ nor bulk signatures of pseudogap closing have as yet been observed. Here, we report electrical transport and specific heat measurements on Sr$_{2-x}$La$_x$IrO$_4$ over an extended doping range 0 $\leq x \leq$ 0.20. The effective carrier density $n_{\rm H}$ at low temperatures exhibits a crossover from $n_{\rm H} \approx x$ to $n_{\rm H} \approx 1+x$ near $x$ = 0.16, accompanied by \textcolor{blue}{a five-orders-of-magnitude increase in conductivity} and a six-fold enhancement in the electronic specific heat. These striking parallels in the bulk pseudogap phenomenology, coupled with the absence of superconductivity in electron-doped Sr$_2$IrO$_4$, disfavour the pseudogap as a state of precursor pairing and thereby narrow the search for the key ingredient underpinning the formation of the superconducting condensate in doped Mott insulators

Genome-wide association studies and genetic architecture of common human diseases

Genome-wide association scans provide the first successful method to identify genetic variation contributing to risk for common complex disease. Progress in identifying genes associated with melanoma show complex relationships between genes for pigmentation and the development of melanoma. Novel risk loci account for only a small fraction of the genetic variation contributing to this and many other diseases. Large meta-analyses find additional variants, but there is current debate about the contribution of common polymorphisms, rare polymorphisms or mutations to disease risk

Phosphate Energy Metabolism During Domoic Acid-Induced Seizures

The effect of domoic acid-induced seizure activity on energy metabolism and on brain pH in mice was studied by continuous EEC recording and in vivo 31 P nuclear magnetic resonance (NMR) spectroscopy. Mice were divided into ventilated (n = 6) and nonventilated (n = 7) groups. Baseline EEG was 0.1-mV amplitude with frequence of >30-Hz and of 4–5 Hz. After intraperitoneal (i.p.) administration of domoic acid (6 mg/kg), electro graphic spikes appeared at increasing frequency, pro gressing to high-amplitude (0.1-0.8 mV) continuous sei zure activity (status epilepticus). In ventilated mice, the [ 31 P]NMR spectra showed that high-energy phosphate levels and tissue pH did not change after domoic acid administration or during the intervals of spiking or status epilepticus. Nonventilated mice showed periods of EEG suppression accompanied by decreases in the levels of high-energy phosphate metabolites and in pH, corresponding to episodic respiratory suppression during the spiking interval. In all animals, status epilepticus was fol lowed by a marked decrease in EEG amplitude that pro gressed rapidly to isoelectric silence. [ 31 P]NMR spectra obtained after this were indicative of total energy failure and tissue acidosis. In a separate group of ventilated mice (n = 4), domoic acid-induced status epilepticus was ac companied initially by an increase in mean arterial blood pressure (MAP) that slowly returned to baseline level. Isoelectric silence was accompanied by a decrease in MAP to 75 ± 8 mm Hg. These experiments suggest that domoic acid-induced seizures are not accompanied by an increase in substrate demand that exceeds supply.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65953/1/j.1528-1157.1993.tb02124.x.pd

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling.

Published version. Copyright © 2008 NIHR Health Technology Assessment ProgrammeOBJECTIVES: To identify combinations of tests and treatments to predict and prevent spontaneous preterm birth. DATA SOURCES: Searches were run on the following databases up to September 2005 inclusive: MEDLINE, EMBASE, DARE, the Cochrane Library (CENTRAL and Cochrane Pregnancy and Childbirth Group trials register) and MEDION. We also contacted experts including the Cochrane Pregnancy and Childbirth Group and checked reference lists of review articles and papers that were eligible for inclusion. REVIEW METHODS: Two series of systematic reviews were performed: (1) accuracy of tests for the prediction of spontaneous preterm birth in asymptomatic women in early pregnancy and in women symptomatic with threatened preterm labour in later pregnancy; (2) effectiveness of interventions with potential to reduce cases of spontaneous preterm birth in asymptomatic women in early pregnancy and to reduce spontaneous preterm birth or improve neonatal outcome in women with a viable pregnancy symptomatic of threatened preterm labour. For the health economic evaluation, a model-based analysis incorporated the combined effect of tests and treatments and their cost-effectiveness. RESULTS: Of the 22 tests reviewed for accuracy, the quality of studies and accuracy of tests was generally poor. Only a few tests had LR+ > 5. In asymptomatic women these were ultrasonographic cervical length measurement and cervicovaginal prolactin and fetal fibronectin screening for predicting spontaneous preterm birth before 34 weeks. In this group, tests with LR- 5 were absence of fetal breathing movements, cervical length and funnelling, amniotic fluid interleukin-6 (IL-6), serum CRP for predicting birth within 2-7 days of testing, and matrix metalloprotease-9, amniotic fluid IL-6, cervicovaginal fetal fibronectin and cervicovaginal human chorionic gonadotrophin (hCG) for predicting birth before 34 or 37 weeks. In this group, tests with LR- < 0.2 included measurement of cervicovaginal IL-8, cervicovaginal hCG, cervical length measurement, absence of fetal breathing movement, amniotic fluid IL-6 and serum CRP, for predicting birth within 2-7 days of testing, and cervicovaginal fetal fibronectin and amniotic fluid IL-6 for predicting birth before 34 or 37 weeks. The overall quality of the trials included in the 40 interventional topics reviewed for effectiveness was also poor. Antibiotic treatment was generally not beneficial but when used to treat bacterial vaginosis in women with intermediate flora it significantly reduced the incidence of spontaneous preterm birth. Smoking cessation programmes, progesterone, periodontal therapy and fish oil appeared promising as preventative interventions in asymptomatic women. Non-steroidal anti-inflammatory agents were the most effective tocolytic agent for reducing spontaneous preterm birth and prolonging pregnancy in symptomatic women. Antenatal corticosteroids had a beneficial effect on the incidence of respiratory distress syndrome and the risk of intraventricular haemorrhage (28-34 weeks), but the effects of repeat courses were unclear. For asymptomatic women, costs ranged from 1.08 pounds for vitamin C to 1219 pounds for cervical cerclage, whereas costs for symptomatic women were more significant and varied little, ranging from 1645 pounds for nitric oxide donors to 2555 pounds for terbutaline; this was because the cost of hospitalisation was included. The best estimate of additional average cost associated with a case of spontaneous preterm birth was approximately 15,688 pounds for up to 34 weeks and 12,104 pounds for up to 37 weeks. Among symptomatic women there was insufficient evidence to draw firm conclusions for preventing birth at 34 weeks. Hydration given to women testing positive for amniotic fluid IL-6 was the most cost-effective test-treatment combination. Indomethacin given to all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among symptomatic women. For a symptomatic woman, the most cost-effective test-treatment combination for postponing delivery by at least 48 h was the cervical length (15 mm) measurement test with treatment with indomethacin for all those testing positive. This combination was also the most cost-effective option for postponing delivery by at least 7 days. Antibiotic treatment for asymptomatic bacteriuria of all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among asymptomatic women but this does not take into account the potential side effects of antibiotics or issues such as increased resistance. CONCLUSIONS: For primary prevention, an effective, affordable and safe intervention applied to all mothers without preceding testing is likely to be the most cost-effective approach in asymptomatic women in early pregnancy. For secondary prevention among women at risk of preterm labour in later pregnancy, a management strategy based on the results of testing is likely to be more cost-effective. Implementation of a treat-all strategy with simple interventions, such as fish oils, would be premature for asymptomatic women. Universal provision of high-quality ultrasound machines in labour wards is more strongly indicated for predicting spontaneous preterm birth among symptomatic women than direct management, although staffing issues and the feasibility and acceptability to mothers and health providers of such strategies need to be explored. Further research should include investigations of low-cost and effective tests and treatments to reduce and delay spontaneous preterm birth and reduce the risk of perinatal mortality arising from preterm birth

Adaptive versus eductive learning: Theory and evidence

Adaptive and eductive learning are two widely used ways of modeling the process by which agents learn a rational expectation equilibrium (REE). In this paper we report an experiment where we exploit differences in the conditions under which adaptive and eductive learning converge to REE so as to investigate which approach provides the better description of the learning behavior of human subjects. Our results suggest that the path by which the system converges appears to be a mixture of both adaptive and eductive learning model predictions.Accepted versio

Review of Inverse Laplace Transform Algorithms for Laplace-Space Numerical Approaches

A boundary element method (BEM) simulation is used to compare the efficiency of numerical inverse Laplace transform strategies, considering general requirements of Laplace-space numerical approaches. The two-dimensional BEM solution is used to solve the Laplace-transformed diffusion equation, producing a time-domain solution after a numerical Laplace transform inversion. Motivated by the needs of numerical methods posed in Laplace-transformed space, we compare five inverse Laplace transform algorithms and discuss implementation techniques to minimize the number of Laplace-space function evaluations. We investigate the ability to calculate a sequence of time domain values using the fewest Laplace-space model evaluations. We find Fourier-series based inversion algorithms work for common time behaviors, are the most robust with respect to free parameters, and allow for straightforward image function evaluation re-use across at least a log cycle of time

Mass and Hot Baryons in Massive Galaxy Clusters from Subaru Weak Lensing and AMiBA SZE Observations

We present a multiwavelength analysis of a sample of four hot (T_X>8keV) X-ray galaxy clusters (A1689, A2261, A2142, and A2390) using joint AMiBA Sunyaev-Zel'dovich effect (SZE) and Subaru weak lensing observations, combined with published X-ray temperatures, to examine the distribution of mass and the intracluster medium (ICM) in massive cluster environments. Our observations show that A2261 is very similar to A1689 in terms of lensing properties. Many tangential arcs are visible around A2261, with an effective Einstein radius \sim 40 arcsec (at z \sim 1.5), which when combined with our weak lensing measurements implies a mass profile well fitted by an NFW model with a high concentration c_{vir} \sim 10, similar to A1689 and to other massive clusters. The cluster A2142 shows complex mass substructure, and displays a shallower profile (c_{vir} \sim 5), consistent with detailed X-ray observations which imply recent interaction. The AMiBA map of A2142 exhibits an SZE feature associated with mass substructure lying ahead of the sharp north-west edge of the X-ray core suggesting a pressure increase in the ICM. For A2390 we obtain highly elliptical mass and ICM distributions at all radii, consistent with other X-ray and strong lensing work. Our cluster gas fraction measurements, free from the hydrostatic equilibrium assumption, are overall in good agreement with published X-ray and SZE observations, with the sample-averaged gas fraction of = 0.133 \pm 0.027, for our sample = (1.2 \pm 0.1) \times 10^{15} M_{sun} h^{-1}. When compared to the cosmic baryon fraction f_b = \Omega_b/\Omega_m constrained by the WMAP 5-year data, this indicates /f_b = 0.78 \pm 0.16, i.e., (22 \pm 16)% of the baryons are missing from the hot phase of clusters.Comment: accepted for publication in ApJ; high resolution figures available at http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/AMiBA7/ms_highreso.pd