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In this study, we examine the key management and scientific traditions that inform the logical framework, a project planning and evaluation tool that is central to how many non-governmental organizations (NGOs) manage their projects and provide accounts to funders. Through an analysis of USAID reports from the 1960s and 1970s, interviews with the logical framework’s developers, and a close reading of seminal texts, we identify how systems theory, management by objectives, and scientific theory informed how USAID problematized its project planning and evaluation practices and how they came to be inscribed into the logical framework as a way to address such perceived problems. We argue that these traditions are important for understanding a particular strand of managerialization that informs international development NGOs, and, more generally, for understanding how funding agencies “see” through the logical framework.
Over the past decade, there has been an increase in the development of innovative cancer treatments that have positively impacted upon mortality rates. However, the approval process at the local level remains lengthy. This study estimated the clinical and economic impact of the availability of innovative therapies for treating advanced lung cancer in men in five Latin American countries.
Methods
Using public data, we analyzed the relationship between available innovative therapies and age-specific mortality rates for Argentina, Brazil, Chile, Colombia, and Mexico through a regression model. By comparing the number of therapies approved by the United States Food and Drug Administration (FDA) with those approved by each local regulatory agency, we estimated the avoidable deaths (ADs) that could have been averted if innovations had been available. We calculated years of life lost (YLLs) based on life expectancy, median age of death, and ADs. Productivity loss was estimated using each country’s retirement age and the annual gross domestic product (GDP) per capita in 2022.
Results
Between 2006 and 2021, the FDA approved 24 innovative treatments for 30 indications. By 2021, only 60 to 77 percent of these therapies were available locally. Total ADs, YLLs, and PL were USD8,694, USD114,477, and USD439,179,876, respectively. The most significant productivity losses were found in Brazil and Argentina due to the large Brazilian population and Argentina’s high GDP per capita. Despite its low population, Chile’s high GDP per capita resulted in considerable productivity loss. Colombia and Mexico showed a notable clinical impact, suggesting the advantages of early approval. Although the availability of FDA-approved therapies has increased, local time lags have recently increased.
Conclusions
Our results highlight the potential of improving regulatory processes to increase the availability of innovative therapies in five Latin American countries. Accelerating the introduction of these therapies for advanced lung cancer presents a major opportunity to enhance survival rates, instilling a sense of hope and optimism while avoiding substantial productivity losses.
The 17-subunit RNA polymerase III (RNAP III) synthesizes essential untranslated RNAs such as tRNAs and 5S rRNA. In yeast and vertebrates, subunit C82 forms a stable subcomplex with C34 and C31 that is necessary for promoter-specific transcription initiation. Little is known about RNAP III transcription in trypanosomatid parasites. To narrow this knowledge gap, we characterized the C82 subunit in Trypanosoma brucei and Leishmania major. Bioinformatic analyses showed that the 4 distinctive extended winged-helix (eWH) domains and the coiled-coil motif are present in C82 in these microorganisms. Nevertheless, C82 in trypanosomatids presents certain unique traits, including an exclusive loop within the eWH1 domain. We found that C82 localizes to the nucleus and binds to RNAP III-dependent genes in the insect stages of both parasites. Knock-down of C82 by RNA interference significantly reduced the levels of tRNAs and 5S rRNA and led to the death of procyclic forms of T. brucei. Tandem affinity purifications with both parasites allowed the identification of several C82-interacting partners, including C34 and some genus-specific putative regulators of transcription. However, the orthologue of C31 was not found in trypanosomatids. Interestingly, our data suggest a strong association of C82 with TFIIIC subunits in T. brucei, but not in L. major.
We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.
Technical summary
The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.
Social media summary
We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.
Dissolved inorganic carbon (DIC) in ocean water is a major sink of fossil fuel derived CO2. Carbon isotopes in DIC serve as tracers for oceanic water masses, biogeochemical processes, and air-sea gas exchange. We present a timeseries of surface DIC δ13C and Δ14C values from 2011 to 2022 from Newport Beach, California. This is a continuation of previous timeseries (Hinger et al. 2010; Santos et al. 2011) that together provide an 18-year record. These data show that DIC Δ14C values have declined by 42‰ and that DIC δ13C values have declined by 0.4‰ since 2004. By 2020, DIC Δ14C values were within analytical error of nearby clean atmospheric CO2 Δ14C values. These long-term trends are likely the result of significant fossil fuel derived CO2 in surface DIC from air-sea gas exchange. Seasonally, Δ14C values varied by 3.4‰ between 2011 and 2022, where seasonal δ13C values varied by 0.7‰. The seasonal variation in Δ14C values is likely driven by variations in upwelling, surface eddies, and mixed layer depth. The variation in δ13C values appears to be driven by isotopic fractionation from marine primary producers. The DIC δ13C and Δ14C values record the influence of the drought that began in 2012, and a major upwelling event in 2016.
Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance.
Methods:
We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education.
Results:
Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory.
Conclusions:
Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.
In resource limited settings, children with cardiac disease present late, have poor outcomes and access to paediatric cardiology programmes is limited. Cardiac point of care ultrasound was introduced at several Médecins Sans Frontières sites to facilitate cardiopulmonary assessment. We describe the spectrum of disease, case management and outcomes of cases reviewed over the Telemedicine platform.
Methods:
Previously ultrasound naïve, remotely placed clinical teams received ultrasound training on focussed image acquisition. The Médecins Sans Frontières Telemedicine platform was utilised for remote case and imaging review to diagnose congenital and acquired heart disease and guide management supported by a remotely situated paediatric cardiologist.
Results:
Two-hundred thirty-three cases were reviewed between 2016 and 2018. Of 191 who underwent focussed cardiac ultrasound, diagnoses included atrial and ventricular septal defects 11%, atrioventricular septal defects 7%, Tetralogy of Fallot 9%, cardiomyopathy/myocarditis 8%, rheumatic heart disease 8%, isolated pericardiac effusion 6%, complex congenital heart disease 4% and multiple other diagnoses in 15%. In 17%, there was no identifiable abnormality while 15% had inadequate imaging to make a diagnosis. Cardiologist involvement led to management changes in 75% of cases with a diagnosis. Mortality in the entire group was disproportionately higher among neonates (38%, 11/29) and infants (20%, 16/81). There was good agreement on independent review of selected cases between two independent paediatric cardiologists.
Conclusion:
Cardiac point of care ultrasound performed by remote clinical teams facilitated diagnosis and influenced management in cases reviewed over a Telemedicine platform. This is a feasible method to support clinical care in resource limited settings.
Impairments in social cognition contribute significantly to disability in schizophrenia patients (SzP). Perception of facial expressions is critical for social cognition. Intact perception requires an individual to visually scan a complex dynamic social scene for transiently moving facial expressions that may be relevant for understanding the scene. The relationship of visual scanning for these facial expressions and social cognition remains unknown.
Methods
In 39 SzP and 27 healthy controls (HC), we used eye-tracking to examine the relationship between performance on The Awareness of Social Inference Test (TASIT), which tests social cognition using naturalistic video clips of social situations, and visual scanning, measuring each individual's relative to the mean of HC. We then examined the relationship of visual scanning to the specific visual features (motion, contrast, luminance, faces) within the video clips.
Results
TASIT performance was significantly impaired in SzP for trials involving sarcasm (p < 10−5). Visual scanning was significantly more variable in SzP than HC (p < 10−6), and predicted TASIT performance in HC (p = 0.02) but not SzP (p = 0.91), differing significantly between groups (p = 0.04). During the visual scanning, SzP were less likely to be viewing faces (p = 0.0001) and less likely to saccade to facial motion in peripheral vision (p = 0.008).
Conclusions
SzP show highly significant deficits in the use of visual scanning of naturalistic social scenes to inform social cognition. Alterations in visual scanning patterns may originate from impaired processing of facial motion within peripheral vision. Overall, these results highlight the utility of naturalistic stimuli in the study of social cognition deficits in schizophrenia.
Little is known about who would benefit from Internet-based personalised nutrition (PN) interventions. This study aimed to evaluate the characteristics of participants who achieved greatest improvements (i.e. benefit) in diet, adiposity and biomarkers following an Internet-based PN intervention. Adults (n 1607) from seven European countries were recruited into a 6-month, randomised controlled trial (Food4Me) and randomised to receive conventional dietary advice (control) or PN advice. Information on dietary intake, adiposity, physical activity (PA), blood biomarkers and participant characteristics was collected at baseline and month 6. Benefit from the intervention was defined as ≥5 % change in the primary outcome (Healthy Eating Index) and secondary outcomes (waist circumference and BMI, PA, sedentary time and plasma concentrations of cholesterol, carotenoids and omega-3 index) at month 6. For our primary outcome, benefit from the intervention was greater in older participants, women and participants with lower HEI scores at baseline. Benefit was greater for individuals reporting greater self-efficacy for ‘sticking to healthful foods’ and who ‘felt weird if [they] didn’t eat healthily’. Participants benefited more if they reported wanting to improve their health and well-being. The characteristics of individuals benefiting did not differ by other demographic, health-related, anthropometric or genotypic characteristics. Findings were similar for secondary outcomes. These findings have implications for the design of more effective future PN intervention studies and for tailored nutritional advice in public health and clinical settings.
In the current work, we compared the green synthesis of silver nanoparticles (AgNP) using plant extracts, a promising methodology against the use of chemical reducers, such as oleic acid and oleylamine. The advantages of green synthesis are one-step method, economic and ecological while the advantages of classic synthesis methods are high nanoparticle performance, homogeneity in size and smaller average sizes. With this work we want to demonstrate that plant extracts with specific mixtures of chemical compounds can obtain smaller average sizes with greater homogeneity in nanoparticles compared to the use of classical synthesis. Myrtillocactus geometrizans was used as a polar plant extract, which was selected by the chemical components contained in the extract. Phytosterols, oleic acid and betalains contained in Myrtillocactus geometrizans are biomolecules responsible for the reduction and stability of AgNP below 5 nm. TEM analysis of the green synthesis of nanoparticles revealed the formation of spherical particles with an average diameter of 5 nm and with preferential crystallographic directions of the silver plane [111].
The present work investigated the application of detailed airborne images and a resistivity soil sensor (Veris 3100) to detect soil and crop spatial variability to assist in orchard management. The research was carried out in a peach orchard (Prunus persica). Soil apparent electrical conductivity (ECa), NDVI from a multispectral image (0.25 m/pixel) and soil properties at 40 sampling points (0–30 cm) were acquired. The ECa was standardized at 25°C. It showed a strong relationship with former landforms, altered by land levelling. A positive correlation of EC25 with EC1:5, water holding capacity at −1500 kPa and soil depth was found. NDVI was correlated only in the textural fractions coarser than clay. Two types of management zones were proposed: a) to improve the water holding capacity of soils and b) to regulate tree vigour and yield.
Eukaryotic 5S rRNA, synthesized by RNA polymerase III (Pol III), is an essential component of the large ribosomal subunit. Most organisms contain hundreds of 5S rRNA genes organized into tandem arrays. However, the genome of the protozoan parasite Leishmania major contains only 11 copies of the 5S rRNA gene, which are interspersed and associated with other Pol III-transcribed genes. Here we report that, in general, the number and order of the 5S rRNA genes is conserved between different species of Leishmania. While in most organisms 5S rRNA genes are normally associated with the nucleolus, combined fluorescent in situ hybridization and indirect immunofluorescence experiments showed that 5S rRNA genes are mainly located at the nuclear periphery in L. major. Similarly, the tandemly repeated 5S rRNA genes in Trypanosoma cruzi are dispersed throughout the nucleus. In contrast, 5S rRNA transcripts in L. major were localized within the nucleolus, and scattered throughout the cytoplasm, where mature ribosomes are located. Unlike other rRNA species, stable antisense RNA complementary to 5S rRNA is not detected in L. major.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Design
Longitudinal study.
Setting
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Subjects
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Results
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Conclusions
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.