Socio-economic assessment of two small-scale irrigation schemes in Adami Tullu Jido Kombolcha Woreda, Central Rift Valley of Ethiopia

The sustainability of irrigated agriculture is questioned and the challenge is to increase simultaneously land and water productivity in the face of the limited availability of land and water in the CRV, the Central Rift Valley. The aim of this research is to assess the social-economic performance of two communitybased small-scale irrigation schemes in Adami Tullu Jido Kombolcha Woreda (ATJK) and to identify options to improve irrigation performance and resource managemen

Immune related endonucleases and GTPases are not associated with tumor response in patients with advanced non-small cell lung cancer treated with checkpoint inhibitors

Immune related endonucleases have recently been described as potential therapeutic targets and predictors of response to treatment with immune checkpoint inhibitors (ICI). The aim is to evaluate the association between the expression of 5 biomarkers involved in the immune response (CD73, CD39, VISTA, Arl4d and Cytohesin-3) in parallel with the more common ICI-predictive markers, PD-L1 expression and Tumor Mutation Burden (TMB) with response to ICI therapy in an advanced non-small cell lung cancer (NSCLC) cohort. METHODS: Patients with advanced NSCLC treated with ICI single agent were divided into responders and non-responders according to RECIST v1.1 and duration of response (DOR) criteria. Immunohistochemistry was performed on pretreatment tumor tissue samples for PD-L1, CD73, CD39, VISTA, Arl4d, and Cytohesin-3 expression. TMB was estimated with NEOplus v2 RUO (NEO New Oncology GmbH) hybrid capture next generation sequencing assay. Resistance mutations in STK11/KEAP1 and positive predictive mutations in ARID1A/POLE were also evaluated. RESULTS: Included were 56 patients who were treated with ICI single agent. The median progression-free and overall survival for the whole cohort was 3.0 (95% CI, 2.4-3.6) and 15 (95% CI, 9.7-20.2) months, respectively. The distribution of CD73 in tumor cells and CD39, VISTA, Arl4d and Cytohesin-3 expression in immune cells were not different between responders and non-responders. Also, PD-L1 and TMB were not predictive for response. The frequency of STK11, KEAP1 and ARID1A mutations was low and only observed in the non-responder group. CONCLUSION: Separate and combined expression of 5 biomarkers involved in the immune response (CD73, CD39, VISTA, Arl4d, and Cytohesin-3) was not associated with response in our cohort of advanced NSCLC patients receiving single agent ICI. To confirm our findings the analysis of independent larger cohorts is warranted

Golden Rice, VAD, Covid and Public Health: Saving Lives and Money

On July 21, 2021, Golden Rice was registered in the Philippines allowing cultivation and consumption. Research, as an intervention to combat vitamin A deficiency (VAD), started in 1991, and proof of concept for what was to become Golden Rice, was achieved in 1999. In the 1990s, 23–34% deaths globally of children less than 5 years old were caused by VAD, and in developing countries, the percentage was even higher. By 2013, progress against the Millennium Development Goals had reduced <5-y child deaths globally from VAD to about 2% of all such deaths. The progress included significant vaccination programs against measles, and better access to clean water, as well as vitamin A supplementation, all delivered through community health programs. Economic development and education about diet reduced food insecurity. In contrast to continuing VAD deaths, the Covid-19 pandemic has attracted huge political attention, including in low- and middle-income countries. Community health programs have been adversely affected by the pandemic. There is a danger that as a result VAD rates, child and maternal mortality climbs again toward 1990’s levels. Adoption of Golden Rice provides a safe, culturally simple amelioration and is costless. Other countries should seize the opportunity. Bangladesh is first in line, possibly followed by Indonesia and India

Donor-acceptor Stenhouse adduct functionalised polymer microspheres

Polymers that carry donor-acceptor Stenhouse adducts (DASAs) are a very relevant class of light-responsive materials. Capable of undergoing reversible, photoinduced isomerisations under irradiation with visible light, DASAs allow for on-demand property changes to be performed in a non-invasive fashion. Applications include photothermal actuation, wavelength-selective biocatalysis, molecular capture and lithography. Typically, such functional materials incorporate DASAs either as dopants or as pendent functional groups on linear polymer chains. By contrast, the covalent incorporation of DASAs into crosslinked polymer networks is under-explored. Herein, we report DASA-functionalised crosslinked styrene-divinylbenzene-based polymer microspheres and investigate their light-induced property changes. This presents the opportunity to expand DASA-material applications into microflow assays, polymer-supported reactions and separation science. Poly(divinylbenzene-co-4-vinylbenzyl chloride-co-styrene) microspheres were prepared by precipitation polymerisation and functionalised via post-polymerisation chemical modification reactions with 3rd generation trifluoromethyl-pyrazolone DASAs to varying extents. The DASA content was verified via 19F solid-state NMR (ssNMR), and DASA switching timescales were probed by integrated sphere UV-Vis spectroscopy. Irradiation of DASA functionalised microspheres led to significant changes in their properties, notably improving their swelling in organic and aqueous environments, dispersibility in water and increasing mean particle size. This work sets the stage for future developments of light-responsive polymer supports in solid-phase extraction or phase transfer catalysis

Europe’s Farm to Fork Strategy and Its Commitment to Biotechnology and Organic Farming: Conflicting or Complementary Goals?

The European Commission's Farm to Fork (F2F) strategy, under the European Green Deal, acknowledges that innovative techniques, including biotechnology, may play a role in increasing sustainability. At the same time, organic farming will be promoted, and at least 25% of the EU's agricultural land shall be under organic farming by 2030. How can both biotechnology and organic farming be developed and promoted simultaneously to contribute to achieving the Sustainable Development Goals (SDGs)? We illustrate that achieving the SDGs benefits from the inclusion of recent innovations in biotechnology in organic farming. This requires a change in the law. Otherwise, the planned increase of organic production in the F2F strategy may result in less sustainable, not more sustainable, food systems

Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer

In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved "precision" drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate; however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC

Probing embryonic development enables the discovery of unique small-molecule bone morphogenetic protein potentiators

We report on the feasibility to harness embryonic development in vitro for the identification of small-molecule cytokine mimetics and signaling activators. Here, a phenotypic, target-agnostic, high throughput assay is presented that probes bone morphogenetic protein (BMP) signaling during mesodermal patterning of embryonic stem cells. The temporal discrimination of BMP- and transforming growth factor-β (TGFβ)-driven stages of cardiomyogenesis underpins a selective, authentic orchestration of BMP cues that can be recapitulated for the discovery of BMP activator chemotypes. Proof of concept is shown from a chemical screen of 7000 compounds, provides a robust hit validation workflow, and afforded 2,3 disubstituted 4H-chromen-4-ones as potent BMP potentiators with osteogenic efficacy. Mechanistic studies suggest that Chromenone 1 enhances canonical BMP outputs at the expense of TGFβ-Smads in an unprecedented manner. Pharmacophoric features were defined, providing a set of novel chemical probes for various applications in (stem) cell biology, regenerative medicine, and basic research on the BMP pathway

Investing in antibiotics to alleviate future catastrophic outcomes : what is the value of having an effective antibiotic to mitigate pandemic influenza?

Over 95% of post-mortem samples from the 1918 pandemic, which caused 50 to 100 million deaths, showed bacterial infection complications. The introduction of antibiotics in the 1940s has since reduced the risk of bacterial infections, but growing resistance to antibiotics could increase the toll from future influenza pandemics if secondary bacterial infections are as serious as in 1918, or even if they are less severe. We develop a valuation model of the option to withhold wide use of an antibiotic until significant outbreaks such as pandemic influenza or foodborne diseases are identified. Using real options theory, we derive conditions under which withholding wide use is beneficial, and calculate the option value for influenza pandemic scenarios that lead to secondary infections with a resistant Staphylococcus aureus strain. We find that the value of withholding an effective novel oral antibiotic can be positive and significant unless the pandemic is mild and causes few secondary infections with the resistant strain or if most patients can be treated intravenously. Although the option value is sensitive to parameter uncertainty, our results suggest that further analysis on a case-by-case basis could guide investment in novel agents as well as strategies on how to use them

Economic Transition and Natural Resource Management in East-and Southeast Asia

Abstract: For several decades the effective and efficient dissemination of new agricultural knowledge among farmers in developing countries has been problematic. Two major programs were implemented in Indonesia, namely The Training and Visit (T&amp;V) Extension Program or The Massive Guidance (BIMAS) Program, from the mid 1960s until the end of the1980s, and the Farmer Field School (FFS) Program, during the 1990s. The main difference between these two programs is that, where the T&amp;V was concerned, farmers were instructed what to do, while the FFS program encouraged and stimulated farmers to make their own decisions. This paper aims to discuss and compare the effectiveness of these two programs with reference to rice production in Indonesia. This paper would like to argue that, for regions where the level of development is still very low, implementing a T&amp;V program instructing farmers what to do is probably more appropriate than an FFS. As for regions where agriculture is relatively developed, an effective FFS program is more appropriate

Post COVID-19 implications on genetic diversity and genomics research & innovation: A call for governance and research capacity. White paper.

This is the final version. Available from the Food and Agriculture Organisation via the DOI in this record. At a time of significant technological change and digitization in the biological sciences, the COVID19 pandemic has highlighted again the inequities in the research and innovation ecosystem. Based on a consultation with an internationally diverse group of stakeholders from multiple fields and professions, and on a broadly representative set of case studies, this report offers a new approach to the global governance of genetic diversity and genomic research and innovation. We recommend that in addition to the many valuable efforts at the macro-policy level and at the micro-level of projects, teams and organizations, the global community concerned with genetic diversity and genomic research and innovation should devise and implement a meso-level initiative that includes three main components: 1. First, it should establish a new professional capacity to govern research and innovation at the meso-level. Governance capacity, built through a networked community of practice, has the benefit of connecting and integrating macrolevel policy intentions with micro-level actions. It facilitates a consistent professional basis from which local and regional level flexibilities can generate new norms of reflection that better integrate multiple synergies, reconcile tensions, recognize inequities, and redress persistent inequalities. 2. Second, the global community should redouble efforts to build research capacity in genomic research and innovation in the Global South and for Indigenous Peoples. Such an effort should be focused on broader programmatic objectives that facilitate cross-national and cross-regional collaboration, as well as enhancing research communities in the Global South and in Indigenous communities. Together, the twin capacities of governance and research can reduce power differentials among diverse actors and support crisisbased imperatives for data openness. 3. Third, we recommend that existing global policy frameworks interface with research governance and capacity investment. This meso-level approach should gain the commitment and support from national and international policy bodies, embedded within existing specific issue-areas (health, agriculture, environment). A new approach, one that can better respond to global crises though more open, inclusive and equitable participation in research and innovation, is necessary to resolve the tensions among openness, innovation and equity that the current discourse on genetic diversity reiterates. Failure to systematically address the social and technical governance challenges will result in further fragmentation, inequity and vulnerability for decades to come. Conversely, investing in the current historical moment of the pandemic to build twin capacities for meso-level governance and research is poised to prevent and/or reduce the impact of future ecological crises, while contributing to planetary sustainability and prosperity in the 21st century for current and future generations.European CommissionAlan Turing Institut