The CGIAR’s Challenge Program Experiences: A Critical Analysis

This document has been prepared by staff of the four Challenge Programs (CPs) established by the CGIAR in 2002-2004 as a contribution to the first meeting of the Consortium Planning Team (CPT) with the Alliance Executive and Deputy Executive (17-20 February 2009)

Is the destruction or removal of atmospheric methane a worthwhile option?

Removing methane from the air is possible, but do the costs outweigh the benefits? This note explores the question of whether removing methane from the atmosphere is justifiable. Destruction of methane by oxidation to CO2 eliminates 97% of the warming impact on a 100-yr time scale. Methane can be oxidized by a variety of methods including thermal or ultraviolet photocatalysis and various processes of physical, chemical or biological oxidizers. Each removal method has energy costs (with the risk of causing embedded CO2 emission that cancel the global warming gain), but in specific circumstances, including settings where air with high methane is habitually present, removal may be competitive with direct efforts to cut fugitive methane leaks. In all cases however, great care must be taken to ensure that the destruction has a net positive impact on the total global warming, and that the resources required would not be better used for stopping the methane from being emitted

Religious Values, Practices and Pregnancy Outcomes: A Comparison of the Impact of Sect and Mainstream Christian Affiliation

In this report 6566 women enrolled in the Mater-University of Queensland Study of Pregnancy (MUSP) were separated into three groups; members of religious sects, Christians who attend church frequently and Christians who are infrequent attenders. These three groups, respectively labelled Christian sects, Christian attenders and lukewarm Christians were compared on a number of social background, lifestyle and pregnancy outcome variables. The sect members appeared to have the most favourable health, lifestyles and healthy babies at delivery, though this latter finding appears attributable to specific characteristics of the mother and her lifestyle. On most measures the children of lukewarm Christians appear to manifest the worst health while Christian attenders form a group whose children's health is between that of sect members and lukewarm Christians

PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data from 9 Studies of Blacks and Whites

PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy. Methods and Results - These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites). Conclusions - PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease