Childhood health and the changing distribution of foreign aid: Evidence from Nigeria’s transition to lower-middle-income status

With sustained economic growth in many parts of the developing world, an increasing number of countries are transitioning away from the most subsidized development finance as they exceed income and other qualification requirements. Cross-country evidence suggests that Development Assistance Committee (DAC) donors view the crossing over of the World Bank’s International Development Association (IDA) eligibility threshold to signal that a country needs less aid, with subsequent reductions in both IDA and other donors’ concessional funding. Within the health sector, it is particularly important to understand the implications of these status changes for children under five years of age since improving early childhood health is critical to fostering health and social and economic development. Therefore, we examine the implications of the IDA transition by measuring the extent t which World Bank commitments—including both IDA and IBRD—are directed to infant and child health needs in Nigeria. Ordinary Least Squares (OLS) models were used in a difference-indifferences (DID) strategy to compare World Bank IBRD/IDA lending before and after the crossover to regions with varying initial levels of under-five and infant need. We find that the infant need orientation of World Bank aid has increased post-crossover. Conversely, alignment of World Bank commitments to regional child needs appears to have diminished after Nigeria crosses the IDA threshold. However, these effects are statistically insignificant and therefore provides inconclusive evidence. This research addresses an important policy question because the transition away from concessional funding mechanisms will result in difficult tradeoffs in allocating limited health resources; without providing conclusive evidence that crossover results in changes in need-based allocation, it does offer an essential path for future research. These results are directly relevant to policy debates about what we know and do not know about aid in transition and health. This research’s value is especially important in the Sustainable Development Goal (SDG) era in understanding how donor exits could derail progress in health improvement

Microsecond dynamics control the HIV-1 Envelope conformation

The HIV-1 Envelope (Env) glycoprotein facilitates host cell fusion through a complex series of receptor-induced structural changes. Although remarkable progress has been made in understanding the structures of various Env conformations, microsecond timescale dynamics have not been studied experimentally. Here, we used time-resolved, temperature-jump small-angle x-ray scattering to monitor structural rearrangements in an HIV-1 Env SOSIP ectodomain construct with microsecond precision. In two distinct Env variants, we detected a transition that correlated with known Env structure rearrangements with a time constant in the hundreds of microseconds range. A previously unknown structural transition was also observed, which occurred with a time constant below 10 μs, and involved an order-to-disorder transition in the trimer apex. Using this information, we engineered an Env SOSIP construct that locks the trimer in the prefusion closed state by connecting adjacent protomers via disulfides. Our findings show that the microsecond timescale structural dynamics play an essential role in controlling the Env conformation with impacts on vaccine design

Involving research participants in a pan-European research initiative: the EPAD participant panel experience

Abstract: Background: Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts. Methods: In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer’s disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs. Results: The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings. Conclusions: The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations

BLAST: Correlations in the Cosmic Far-Infrared Background at 250, 350, and 500 microns Reveal Clustering of Star-Forming Galaxies

We detect correlations in the cosmic far-infrared background due to the clustering of star-forming galaxies in observations made with the Balloon-borne Large Aperture Submillimeter Telescope, BLAST, at 250, 350, and 500 microns. We perform jackknife and other tests to confirm the reality of the signal. The measured correlations are well fit by a power law over scales of 5-25 arcminutes, with Delta I/I = 15.1 +/- 1.7%. We adopt a specific model for submillimeter sources in which the contribution to clustering comes from sources in the redshift ranges 1.3 <= z <= 2.2, 1.5 <= z <= 2.7, and 1.7 <= z <= 3.2, at 250, 350, and 500 microns, respectively. With these distributions, our measurement of the power spectrum, P(k_theta), corresponds to linear bias parameters, b = 3.8 +/- 0.6, 3.9 +/- 0.6 and 4.4 +/- 0.7, respectively. We further interpret the results in terms of the halo model, and find that at the smaller scales, the simplest halo model fails to fit our results. One way to improve the fit is to increase the radius at which dark matter halos are artificially truncated in the model, which is equivalent to having some star-forming galaxies at z >= 1 located in the outskirts of groups and clusters. In the context of this model we find a minimum halo mass required to host a galaxy is log (M_min / M_sun) = 11.5 (+0.4/-0.1), and we derive effective biases $b_eff = 2.2 +/- 0.2, 2.4 +/- 0.2, and 2.6 +/- 0.2, and effective masses log (M_eff / M_sun) = 12.9 +/- 0.3, 12.8 +/- 0.2, and 12.7 +/- 0.2, at 250, 350, and 500 microns, corresponding to spatial correlation lengths of r_0 = 4.9, 5.0, and 5.2 +/- 0.7 h^-1 Mpc, respectively. Finally, we discuss implications for clustering measurement strategies with Herschel and Planck.Comment: Accepted for publication in the Astrophysical Journal. Maps and other results available at http://blastexperiment.info

A global database of Holocene paleotemperature records

A comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in data-sparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. The multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database. This database can be used to reconstruct the spatiotemporal evolution of Holocene temperature at global to regional scales, and is publicly available in Linked Paleo Data (LiPD) format.Fil: Kaufman, Darrell. Northern Arizona University.; Estados UnidosFil: McKay, Nicholas. Northern Arizona University.; Estados UnidosFil: Routson, Cody. Northern Arizona University.; Estados UnidosFil: Erb, Michael. Northern Arizona University.; Estados UnidosFil: Davis, Basil. University Of Lausanne; SuizaFil: Heiri, Oliver. University Of Basel; SuizaFil: Jaccard, Samuel. University Of Bern; SuizaFil: Tierney, Jessica. University of Arizona; Estados UnidosFil: Dätwyler, Christoph. University Of Bern; SuizaFil: Axford, Yarrow. Northwestern University; Estados UnidosFil: Brussel, Thomas. University of Utah; Estados UnidosFil: Cartapanis, Olivier. University Of Bern; SuizaFil: Chase, Brian. Universite de Montpellier; FranciaFil: Dawson, Andria. Mount Royal University; CanadáFil: de Vernal, Anne. Université du Québec a Montreal; CanadáFil: Engels, Stefan. University of London; Reino UnidoFil: Jonkers, Lukas. University Of Bremen; AlemaniaFil: Marsicek, Jeremiah. University of Wisconsin-Madison; Estados UnidosFil: Moffa Sánchez, Paola. University of Durham; Reino UnidoFil: Morrill, Carrie. University of Colorado; Estados UnidosFil: Orsi, Anais. Université Paris-Saclay; FranciaFil: Rehfeld, Kira. Heidelberg University; AlemaniaFil: Saunders, Krystyna. Australian Nuclear Science And Technology Organisation; AustraliaFil: Sommer, Philipp. University Of Lausanne; SuizaFil: Thomas, Elizabeth. University At Buffalo; Estados UnidosFil: Tonello, Marcela Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Tóth, Mónika. Balaton Limnological Institute; HungríaFil: Vachula, Richard. Brown University; Estados UnidosFil: Andreev, Andrei. Alfred Wegener Institut Helmholtz Centre for Polar and Marine Research; AlemaniaFil: Bertrand, Sebastien. Ghent University; BélgicaFil: Massaferro, Julieta. Administración de Parques Nacionales. Parque Nacional "Nahuel Huapi"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Involving research participants in a pan-European research initiative: the EPAD participant panel experience.

BACKGROUND: Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts. METHODS: In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer's disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs. RESULTS: The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings. CONCLUSIONS: The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations

Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes

Detection of somatic mutations in human leukocyte antigen (HLA) genes using whole-exome sequencing (WES) is hampered by the high polymorphism of the HLA loci, which prevents alignment of sequencing reads to the human reference genome. We describe a computational pipeline that enables accurate inference of germline alleles of class I HLA-A, B and C genes and subsequent detection of mutations in these genes using the inferred alleles as a reference. Analysis of WES data from 7,930 pairs of tumor and healthy tissue from the same patient revealed 298 nonsilent HLA mutations in tumors from 266 patients. These 298 mutations are enriched for likely functional mutations, including putative loss-of-function events. Recurrence of mutations suggested that these \u27hotspot\u27 sites were positively selected. Cancers with recurrent somatic HLA mutations were associated with upregulation of signatures of cytolytic activity characteristic of tumor infiltration by effector lymphocytes, supporting immune evasion by altered HLA function as a contributory mechanism in cancer

Plunge Show Card

Haggerty Gallery Inaugural Opening. Show Card for Plunge.https://digitalcommons.udallas.edu/plunge/1000/thumbnail.jp

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead