Defining and identifying per-protocol effects in randomized trials

In trials with noncompliance to assigned treatment, researchers might be interested in estimating a per-protocol effect - a comparison of two counterfactual outcomes defined by treatment assignment and (often time-varying) compliance with a well-defined treatment protocol. Here, we provide a general counterfactual definition of a per-protocol effect and discuss examples of per-protocol effects that are of either substantive or methodologic interest. In doing so, we seek to make more concrete what per-protocol effects are and highlight that one can estimate per-protocol effects that are more than just a comparison of always taking treatment in two distinct treatment arms. We then discuss one set of identifiability conditions that allow for identification of a causal per-protocol effect, highlighting some potential violations of those conditions that might arise when estimating per-protocol effects

Diet quality indices for research in low- and middle-income countries: a systematic review

Nutrition insecurity among urban poor in modernizing Asian metropolises is a critical issue. It is well recognized that in urban Asia the poor are food insecure. Across Asia the food retail environment is transforming rapidly, in which supermarkets increasingly replace traditional food vending, like markets and street vendors that the urban poor depend upon. The question is, how these transformations impact the diets of the urban poor? What drives their food choice? What are their daily shopping practices and how does that affect their dietary intake? To investigate this, we developed a cross-disciplinary nutrition and social practices study with a sequential quantitative-qualitative mixed-method design. Building on empirical evidence from Hanoi, Vietnam, the study links (i) food choice and measured dietary intake, with (ii) food retail environment, through (iii) food shopping practices and preferences of 400 women of reproductive age within the context of (iv) their transformative urban lifestyles. Methods included are a retail census with GPS coordinates to map the food retail environment, a household survey, a 24-h diet recall, multi-generation household interviews and shopping trips. We demonstrate that integrated sociological and nutritional perspectives are productive in rapidly generating evidence to comprehend the complex trade-offs between food safety and nutrition in everyday food consumption practices. We describe and reflect on our theoretical mix of dietary intake and social practices research, and our holistic mixed method approach which besides combining quantitative and qualitative methods, also voices the urban poor first hand

Optimal designs for rational function regression

We consider optimal non-sequential designs for a large class of (linear and nonlinear) regression models involving polynomials and rational functions with heteroscedastic noise also given by a polynomial or rational weight function. The proposed method treats D-, E-, A-, and $\Phi_p$-optimal designs in a unified manner, and generates a polynomial whose zeros are the support points of the optimal approximate design, generalizing a number of previously known results of the same flavor. The method is based on a mathematical optimization model that can incorporate various criteria of optimality and can be solved efficiently by well established numerical optimization methods. In contrast to previous optimization-based methods proposed for similar design problems, it also has theoretical guarantee of its algorithmic efficiency; in fact, the running times of all numerical examples considered in the paper are negligible. The stability of the method is demonstrated in an example involving high degree polynomials. After discussing linear models, applications for finding locally optimal designs for nonlinear regression models involving rational functions are presented, then extensions to robust regression designs, and trigonometric regression are shown. As a corollary, an upper bound on the size of the support set of the minimally-supported optimal designs is also found. The method is of considerable practical importance, with the potential for instance to impact design software development. Further study of the optimality conditions of the main optimization model might also yield new theoretical insights.Comment: 25 pages. Previous version updated with more details in the theory and additional example

The Pediatric Cell Atlas: defining the growth phase of human development at single-cell resolution

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan

ARDD 2020: from aging mechanisms to interventions

Aging is emerging as a druggable target with growing interest from academia, industry and investors. New technologies such as artificial intelligence and advanced screening techniques, as well as a strong influence from the industry sector may lead to novel discoveries to treat age-related diseases. The present review summarizes presentations from the 7th Annual Aging Research and Drug Discovery (ARDD) meeting, held online on the 1st to 4th of September 2020. The meeting covered topics related to new methodologies to study aging, knowledge about basic mechanisms of longevity, latest interventional strategies to target the aging process as well as discussions about the impact of aging research on society and economy. More than 2000 participants and 65 speakers joined the meeting and we already look forward to an even larger meeting next year. Please mark your calendars for the 8th ARDD meeting that is scheduled for the 31st of August to 3rd of September, 2021, at Columbia University, USA

Search for heavy Majorana or Dirac neutrinos and right-handed W gauge bosons in final states with charged leptons and jets in pp collisions at √s = 13 TeV with the ATLAS detector

A search for heavy right-handed Majorana or Dirac neutrinos NR and heavy right-handed gauge bosons WR is performed in events with energetic electrons or muons, with the same or opposite electric charge, and energetic jets. The search is carried out separately for topologies of clearly separated final-state products (“resolved” channel) and topologies with boosted final states with hadronic and/or leptonic products partially overlapping and reconstructed as a large-radius jet (“boosted” channel). The events are selected from pp collision data at the LHC with an integrated luminosity of 139 fb−1 collected by the ATLAS detector at √s = 13 TeV. No significant deviations from the Standard Model predictions are observed. The results are interpreted within the theoretical framework of a left-right symmetric model, and lower limits are set on masses in the heavy righthanded WR boson and NR plane. The excluded region extends to about m(WR) = 6.4 TeV for both Majorana and Dirac NR neutrinos at m(NR) < 1 TeV. NR with masses of less than 3.5 (3.6) TeV are excluded in the electron (muon) channel at m(WR) = 4.8 TeV for the Majorana neutrinos, and limits of m(NR) up to 3.6 TeV for m(WR) = 5.2 (5.0) TeV in the electron (muon) channel are set for the Dirac neutrinos. These constitute the most stringent exclusion limits to date for the model considered