Walking the last mile on the long road to evidence-informed development: building capacity to use research evidence

The systematic application of rigorous evidence to inform the design and implementation of development policies and programmes has the potential to positively influence development outcomes. To achieve such evidence-informed development, a process of generating, transmitting, and using high-quality, policy-relevant evidence of development effectiveness is required. This article focuses on the final step in this casual chain – the use of evidence by national development policymakers. It proposes a people- and demandfocused approach to capacity building for the use of research evidence by policymakers. This support in building personal as well as team capacity and demand is assumed to encourage a growing institutionalisation of evidence use. The article integrates these capacity-building efforts into the wider theory of change for evidence-informed development, highlighting the importance of effective mechanisms to encourage research use in order to achieve the objective of improving lives through research evidence

Semiquantitative Estimates of Rainfall Variability During the 8.2 kyr Event in California Using Speleothem Calcium Isotope Ratios

A multiproxy record from a fast-growing stalagmite reveals variable hydroclimate on the California coast across the 8.2 kyr event and a precursor event likely caused by initial drainage of proglacial Lake Agassiz. Using speleothem δ Ca, we develop the first semiquantitative estimates of paleorainfall variability for California through calibration with measurements of the modern climate and cave environment. We find that the magnitude of rainfall variability during the 8.2 kyr event approached the multiyear variability observable in the recent past (1950–2019) and the magnitude of variability during the precursor event likely exceeded this range. Additionally, we observe other instances of multidecadal variability comparable in magnitude to the precursor event during the record. Our work suggests that speleothem calcium isotope ratios are a powerful semiquantitative means to reconstruct paleorainfall, although numerous factors must be assessed in each cave system before applying this approach. 4

Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

Dynamical downscaling of austral summer climate forecasts over southern Africa using a regional coupled model

The prediction skill of dynamical downscaling is evaluated for climate forecasts over southern Africa using the Advanced Research Weather Research and Forecasting (WRF) model. As a case study, forecasts for the December–February (DJF) season of 2011/12 are evaluated. Initial and boundary conditions for the WRF model were taken from the seasonal forecasts of the Scale Interaction Experiment-Frontier Research Center for Global Change (SINTEX-F) coupled general circulation model. In addition to sea surface temperature (SST) forecasts generated by nine-member ensemble forecasts of SINTEX-F, the WRF was also configured to use SST generated by a simple mixed layer Price–Weller–Pinkel ocean model coupled to the WRF model. Analysis of the ensemble mean shows that the uncoupled WRF model significantly increases the biases (errors) in precipitation forecasted by SINTEX-F. When coupled to a simple mixed layer ocean model, the WRF model improves the spatial distribution of precipitation over southern Africa through a better representation of the moisture fluxes. Precipitation anomalies forecasted by the coupled WRF are seen to be significantly correlated with the observed precipitation anomalies over South Africa, Zimbabwe, southern Madagascar, and parts of Zambia and Angola. This is in contrast to the SINTEX-F global model precipitation anomaly forecasts that are closer to observations only for parts of Zimbabwe and South Africa. Therefore, the dynamical downscaling with the coupled WRF adds value to the SINTEX-F precipitation forecasts over southern Africa. However, the WRF model yields positive biases (>2°C) in surface air temperature forecasts over the southern African landmass in both the coupled and uncoupled configurations because of biases in the net heat fluxesThe Japan Science and Technology Agency (JST)/Japan International Cooperation Agency (JICA) through the Science and Technology Research Partnership for Sustainable Development (SATREPS).http://www2.ametsoc.org/ams/index.cfm/publications/journals/journal-of-climate/hb2016Geography, Geoinformatics and Meteorolog

The Relationship between Population Structure and Aluminum Tolerance in Cultivated Sorghum

Background: Acid soils comprise up to 50% of the world's arable lands and in these areas aluminum (Al) toxicity impairs root growth, strongly limiting crop yield. Food security is thereby compromised in many developing countries located in tropical and subtropical regions worldwide. In sorghum, SbMATE, an Al-activated citrate transporter, underlies the Alt(SB) locus on chromosome 3 and confers Al tolerance via Al-activated root citrate release. Methodology: Population structure was studied in 254 sorghum accessions representative of the diversity present in cultivated sorghums. Al tolerance was assessed as the degree of root growth inhibition in nutrient solution containing Al. A genetic analysis based on markers flanking Alt(SB) and SbMATE expression was undertaken to assess a possible role for Alt(SB) in Al tolerant accessions. In addition, the mode of gene action was estimated concerning the Al tolerance trait. Comparisons between models that include population structure were applied to assess the importance of each subpopulation to Al tolerance. Conclusion/Significance: Six subpopulations were revealed featuring specific racial and geographic origins. Al tolerance was found to be rather rare and present primarily in guinea and to lesser extent in caudatum subpopulations. Alt(SB) was found to play a role in Al tolerance in most of the Al tolerant accessions. A striking variation was observed in the mode of gene action for the Al tolerance trait, which ranged from almost complete recessivity to near complete dominance, with a higher frequency of partially recessive sources of Al tolerance. A possible interpretation of our results concerning the origin and evolution of Al tolerance in cultivated sorghum is discussed. This study demonstrates the importance of deeply exploring the crop diversity reservoir both for a comprehensive view of the dynamics underlying the distribution and function of Al tolerance genes and to design efficient molecular breeding strategies aimed at enhancing Al tolerance.CGIAR[G3007.04]McKnight FoundationFundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)National Council for Scientific and Technological Development (CNPq

A double-blind comparative study of the safety and efficacy of caspofungin versus micafungin in the treatment of candidiasis and aspergillosis

The safety and efficacy profile of caspofungin and micafungin in Japanese patients with fungal infections were directly compared in this prospective, randomized, double-blind study. The proportion of patients who developed significant drug-related adverse event(s) (defined as a serious drug-related adverse event or a drug-related adverse event leading to study therapy discontinuation) was compared in 120 patients [caspofungin 50 mg, or 50 mg following a 70-mg loading dose on Day 1 (hereinafter, 70/50 mg) group: 60 patients; micafungin 150 mg: 60 patients]. The overall response rate was primarily evaluated in the per-protocol set (PPS) population. The proportion of patients who developed significant drug-related adverse events was 5.0 % (3/60) in the caspofungin group and 10.0 % (6/60) in the micafungin group [95 % confidence interval (CI) for the difference: -15.9 %, 5.2 %]. The favorable overall response in the PPS population for patients with esophageal candidiasis, invasive candidiasis, and chronic pulmonary aspergillosis including aspergilloma was 100.0 % (6/6), 100.0 % (3/3), and 46.7 % (14/30) in the caspofungin group, and 83.3 % (5/6), 100.0 % (1/1), and 42.4 % (14/33) in the micafungin group, respectively. In Japanese patients with Candida or Aspergillus infections, there was no statistical difference in the safety between caspofungin and micafungin. Consistent with other data on these two agents, the efficacy of caspofungin and micafungin was similar

Galactic cosmic radiation in the interplanetary space through a modern secular minimum

Recent solar conditions indicate a persistent decline in solar activity—possibly similar to thepast solar grand minima. During such periods of low solar activity, the fluxes of galactic cosmic rays(GCRs) increase remarkably, presenting a hazard for long-term crewed space missions. We used data fromthe Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter(LRO) to examine the correlation between the heliospheric magnetic field, solar wind speed, and solarmodulation potential of the GCRs through Cycle 24. We used this correlation to project observations frompast secular solar minima, including the Dalton minimum (1790–1830) and the Gleissberg minimum(1890–1920), into the next cycle. For the case of conditions similar to the Dalton (or Gleissberg) minimum,the heliospheric magnetic field could drop to 3.61 (or 4.06) nT, leading to a dose rate increase of75% (or34%). We showed that accounting for a floor in the modulation potential, invoked by the Badhwar-O'Neill2014 model, moderates the projected radiation levels in Cycle 25. We used these results to determine themost conservative permissible mission duration (PMD,290.4+37.7−35.9and 204.3+26.6−25.2days for 45-year-old maleand female astronauts, respectively) based on a 3% risk of exposure-induced death (REID) at the upper95% confidence interval in interplanetary space

Dissecting the Autocrine and Paracrine Roles of the CCR2-CCL2 Axis in Tumor Survival and Angiogenesis

The CCL2 CCR2 axis is likely to contributes to the development and progression of cancer diseases by two major mechanisms; autocrine effect of CCL2 as a survival/growth factor for CCR2+ cancer cells and, the attraction of CCR2+ CX3CR1+tumor associated macrophages that in the absence of CCR2 hardly migrate. Thus far no in vivo system has been set up to differentiate the selective contribution of each of these features to cancer development. Here we employed a chimera animal model in which all non-malignant cells are CCR2−/−, but all cancer cells are CCR2+, combined with an adoptive transfer system of bone marrow (BM) CX3CR1+ cells from CCR2+ mice harboring a targeted replacement of the CX3CR1gene by an enhanced green fluorescent protein (EGFP) reporter gene (cx3cr1gfp), together with the CD45.1 congene. Using this system we dissected the selective contribution of CX3CR1+CCR2+ cells, which comprise only about 7% of CD11b+ BM cells, to tumor development and angiogenesis. Showing that aside for their direct pro-angiogenic effect they are essential for the recruitment of other CD11b+ cells to the tumor site. We further show that the administration of CCR2-Ig, that selectively and specifically neutralize CCL2, to mice in which CCR2 is expressed only on tumor cells, further suppressed tumor development, implicating for the key role of this chemokine supporting tumor survival in an autocrine manner. This further emphasizes the important role of CCL2 as a target for therapy of cancer diseases