WIDER Advisory Group on International Economic Issues

(A research and training centre of the United Nations University

A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE):a multicentre, open-label randomised controlled trial

Background: Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies. Methods: PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP &gt;upper limit of normal or faecal calprotectin ≥200 μg/g, or both), while remission was the converse—ie, quiescent symptoms (HBI &lt;5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin &lt;200 μg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228). Findings: Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0–191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker–treatment interaction effect (absolute difference 1 percentage points, 95% CI –15 to 15; p=0·944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p&lt;0·0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infections (three vs eight). Interpretation: Top-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease. Funding: Wellcome and PredictImmune Ltd.</p

Foreign Portfolio Investment in Emerging Equity Markets

It is increasingly appreciated that improved markets for investment in equities can help promote faster economic growth. Such improvement also allows the ordinary saver to share in that growth. The past decade has seen quite extraordinary expansion in equity markets in a whole range of countries and cross border investment has expanded even faster than investment in domestic equities. One important purpose of this report is to address the question as to whether developing countries can expect to attract net flows of private portfolio capital in any significant amount to their emerging equity markets. The answer of this report is clearly affirmative. As part of the rapid development of a global securities industry, a wide range of developing countries including low income and highly indebted countries can expect to be able to attract a portion of the flows invested in foreign markets by investors from the world's major financial centres. But to do this successfully, each country will have to compete for investor attention with other markets; that is, address a critical shortage of suitable stock, reduce obstacles to access and take actions to support the development of their markets; development which is in any event required for sound domestic reasons. The report focuses on these questions and makes a number of recommendations to the developing countries themselves and to the international community. The issues which developing countries have to address in fostering the growth of their capital markets and in creating conditions attractive for foreign investors as well as for domestic investors are by no means unique to developing countries. On the contrary, many of the issues apply to varying degrees to the markets in developed countries. The difficult and long standing nature of some of the problems is apparent from the fact that developed countries continue to grapple with them — not necessarily always with success

Linking Housing Policy, Housing Typology, and Residential Energy Demand in the United States

Residential energy demand can be greatly influenced by the types of housing structures that households live in, but few studies have assessed changes in the composition of housing stocks as a strategy for reducing residential energy demand or greenhouse gas (GHG) emissions. In this paper we examine the effects of three sequenced federal policies on the share of new housing construction by type in the U.S., and estimate the cumulative influence of those policies on the composition of the 2015 housing stock. In a counterfactual 2015 housing stock without the policy effects, 14 million housing units exist as multifamily rather than single-family, equal to 14.1% of urban housing. Accompanied by floor area reductions of 0–50%, the switch from single- to multifamily housing reduces energy demand by 27–47% per household, and total urban residential energy by 4.6–8.3%. This paper is the first to link federal policies to housing outcomes by type and estimate associated effects on residential energy and GHG emissions. Removing policy barriers and disincentives to multifamily housing can unlock a large potential for reducing residential energy demand and GHG emissions in the coming decades

Drivers of change in US residential energy consumption and greenhouse gas emissions, 1990-2015

Annual greenhouse gas (GHG) emissions from residential energy use in the United States peaked in 2005 at 1.26 Gt CO2-eq yr−1, and have since decreased at an average annual rate of 2% yr−1 to 0.96 Gt CO2-eq yr−1 in 2019. In this article we decompose changes in US residential energy supply and GHG emissions over the period 1990–2015 into relevant drivers for four end-use categories. The chosen drivers encompass changing demographics, housing characteristics, energy end-use intensities, and generation efficiency and GHG intensity of electricity. Reductions in household size, growth in heated floor area per house, and increased access to space cooling are the main drivers of increases in energy and GHG emissions after population growth. Growing shares of newer homes, and reductions in intensity of energy use per capita, household, or floor area have produced moderate primary energy and GHG emission reductions, but improved generation efficiency and decarbonization of electricity supply have brought about far bigger primary energy and GHG emission reductions. Continued decline of residential emissions from electrification of residential energy and decarbonization of electricity supply can be expected, but not fast enough to limit climate change to 1.5 °C warming. US residential final energy demand will therefore need to decline in absolute terms to meet such a target. However, without changes in the age distribution, type mix, or average size of housing, improvements in energy efficiency are unlikely to outweigh growth in the number of households from population growth and further household size reductions

QMCPACK : an open source ab initio quantum Monte Carlo package for the electronic structure of atoms, molecules and solids

International audienceQMCPACK is an open source quantum Monte Carlo package for ab-initio electronic structure calculations. It supports calculations of metallic and insulating solids, molecules, atoms, and some model Hamiltonians. Implemented real space quantum Monte Carlo algorithms include variational, diffusion, and reptation Monte Carlo. QMCPACK uses Slater-Jastrow type trial wave functions in conjunction with a sophisticated optimizer capable of optimizing tens of thousands of parameters. The orbital space auxiliary field quantum Monte Carlo method is also implemented, enabling cross validation between different highly accurate methods. The code is specifically optimized for calculations with large numbers of electrons on the latest high performance computing architectures, including multicore central processing unit (CPU) and graphical processing unit (GPU) systems. We detail the program's capabilities, outline its structure, and give examples of its use in current research calculations. The package is available at http://www.qmcpack.org