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The viability of small island developing states (SIDS) is threatened by three distinct processes – a backlash against globalisation; rising geopolitical competition between powers; and accelerating climate change – which are pulling at the threads binding the liberal international order together. We suggest that this order has been kinder to SIDS than is often acknowledged because its underpinning norms – sovereign equality, non-interference, and right to development – are inherently permissive and thus provide SIDS with choices rather than imperatives. Their leaders should fight for the continuation and enhancement of that order rather than be seduced by alternatives. We provide a rationale for and examples of policies to achieve this, including reforms to the way ODA is measured, debt restructured, climate finance allocated, and global governance organised. These enhancements represent the most plausible pathway for SIDS in a period of significant global upheaval. This title is also available as Open Access on Cambridge Core.
End members and species defined with permissible ranges of composition are presented for the true micas, the brittle micas and the interlayer-cation-deficient micas. The determination of the crystallochemical formula for different available chemical data is outlined, and a system of modifiers and suffixes is given to allow the expression of unusual chemical substitutions or polytypic stacking arrangements. Tables of mica synonyms, varieties, ill-defined materials and a list of names formerly or erroneously used for micas are presented. The Mica Subcommittee was appointed by the Commission on New Minerals and Mineral Names (“Commission”) of the International Mineralogical Association (IMA). The definitions and recommendations presented were approved by the Commission.
OBJECTIVES/GOALS: The EWSR1-FLI1 gene fusion is implicated as a source of oncogenic activity in the majority of Ewing sarcoma (EwS) cases (>70%). Our studies will provide unparalleled insight into the transformative mechanics of EWS-FLI1 METHODS/STUDY POPULATION: EWS-FLI1 is an intrinsically disordered protein (IDP). IDPs do not form stable secondary or tertiary folds in biological conditions and ofter contain proline-rich regions and other multivalent binding regions. These regions interact with numerous partners resulting in highly dynamic and complex protein-protein interactions. Recent advances in proximity labelling techniques, such as the use of a biotin ligase fused to a protein of interest are exceptionally well suited to identifying IDP interactomes since they do not rely on the binding affinities but rather the distance between interacting proteins. Combining novel discovery proteomics with Nuclear Magnetic Resonance (NMR) approaches will provide unparalleled insight into the transformative mechanics of EWS-FLI1. RESULTS/ANTICIPATED RESULTS: Using the proximity labeling technique TurboID, which limits the number of false-positive interactions, we have shown that EWSR1 and EWS-FLI1 act within the spliceosome (responsible for mRNA splicing and processing). Using bioinformatics techniques, we show EWS-FLI1 interacts with peptidyl-prolyl isomerase (PPI) proteins, specifically PPIL1, through the EWS-FLI1 N-terminal region (EWS-LCD). We used NMR to provide insight into the interaction between PPIL1 and EWS-LCD, showing that EWS-LCD interacts with the catalytic region of PPIL1. We anticipate that PPIL1 isomerizes EWS-FLI1 to modulate its activity, and that EWS-FLI1 interacts with the spliceosome through formation of a biological condensate. However, future proximity labeling and NMR studies are needed to verify this activity. DISCUSSION/SIGNIFICANCE: Our studies will yield actionable insights regarding the protein-protein interfaces in EWS-FLI1 that can be targeted to attenuate the oncogenic activity of EWS-FLI1. More broadly, our results will be applicable toward understanding the etiology of other pediatric cancers and for guiding the development of novel targeted treatments.
Transposition of great arteries with intact ventricular septum and left ventricular outflow tract obstruction (TGA + IVS + LVOTO) is uncommon. We reviewed operations performed in patients with TGA + IVS + LVOTO in the European Congenital Heart Surgeons Association Congenital Database (ECHSA-CD).
Methods:
All 109 patients with a diagnosis of TGA + IVS + LVOTO in ECHSA-CD who underwent cardiac surgery during a 21-year period (01/2000-02/2021, inclusive) were included. Preoperative variables, operative data, and postoperative outcomes were collected.
Results:
These 109 patients underwent 176 operations, including 37 (21.0%) arterial switch operations (ASO), 26 (14.2%) modified Blalock-Taussig-Thomas shunts (MBTTS), 11 (6.2%) Rastelli operations, and 13 (7.3%) other palliative operations (8 superior cavopulmonary anastomosis[es], 4 Fontan, and 1 other palliative procedure). Of 37 patients undergoing ASO, 22 had a concomitant procedure.
There were 68 (38.6%) reoperations, including 11 pacemaker procedures and 8 conduit operations. After a systemic-to-pulmonary artery shunt, reoperations included shunt reoperation (n = 4), Rastelli (n = 4), and superior cavopulmonary anastomosis (n = 3).
Overall Operative Mortality was 8.2% (9 deaths), including three following ASO, two following “Nikaidoh, Kawashima, or LV-PA conduit” procedures, and two following Rastelli. Postoperative complications occurred after 36 operations (20.4%). The most common complications were delayed sternal closure (n = 11), postoperative respiratory insufficiency requiring mechanical ventilation >7 days (n = 9), and renal failure requiring temporary dialysis (n = 8).
Conclusion:
TGA + IVS + LVOTO is rare (109 patients in ECHSA-CD over 21 years). ASO, MBTTS, and Rastelli are the most common operations performed for TGA + IVS + LVOTO. Larger international studies with long-term follow-up are needed to better define the anatomy of the LVOTO and to determine the optimal surgical strategy.
Since the 1980s, the Upper Jurassic lithographic limestone of the Causse Méjean (southern France) has been known by local naturalists to yield fossils. However, until the beginning of the 21st century, this plattenkalk remained largely undersampled and scientifically underestimated. Here, we present the results of two decades of prospection and sampling in the Drigas and the Nivoliers quarries. We provide the first palaeontological inventory of the fossil flora, the fauna and the ichnofauna for these localities. The fossil assemblages show the co-occurrence of marine and terrestrial organisms. Marine organisms include algae, bivalves, brachiopods, cephalopods (ammonites, belemnites and coleoids such as Trachyteuthis), echinoderms, decapod crustaceans (ghost shrimps, penaeoid shrimps and glypheoid lobsters) and fishes (including several actinopterygians and a coelacanth). Terrestrial organisms consist of plant remains (conifers, bennettitaleans, pteridosperms) and a single rhynchocephalian (Kallimodon cerinensis). Ichnofossils comprise traces of marine invertebrates (e.g. limulid trackways, ammonite touch mark) as well as coprolites and regurgitalites. Given the exquisite preservation of these fossils, the two quarries can be considered as Konservat-Lagerstätten. Both lithological features and fossil content suggest a calm, protected and shallow-marine environment such as a lagoon partially or occasionally open to the sea. Most fossils are allochthonous to parautochthonous and document diverse ecological habitats. Similarly to other famous Upper Jurassic plattenkalks of western Europe such as Solnhofen, Cerin or Canjuers, the Causse Méjean is a key landmark for our understanding of coastal/lagoonal palaeoecosystems during the Kimmeridgian–Tithonian interval.
The Caribbean has seen a dramatic shift in the obesity and chronic disease prevalence over the past decades, suggesting a nutrition transition. Simultaneously, Martinique has faced a demographic transition marked by significant population ageing. We aimed to differentiate the contribution of changes in health status and dietary intakes due to shifts in demographic and socio-economic characteristics (DSEC) from that due to unobserved factors.
Design:
Two cross-sectional surveys conducted in 2003 (n 743) and 2013 (n 573) on representative samples were used. Dietary intakes were estimated by 24-h recalls. The contribution of changes in health status and dietary intakes due to shifts in observed DSEC was differentiated from that due to unobserved factors over a 10-year interval, using Oaxaca–Blinder decomposition models.
Setting:
Martinique, French region in the Caribbean.
Participants:
Martinican adults (≥16 years).
Results:
Over the study period, health status deteriorated, partly owing to shifts in DSEC, explaining 62 % of the change in the prevalence of hypertension (+13 percentage points (pp)) and 48 % of waist circumference change (+3 cm). Diet quality decreased (mean adequacy ratio –2pp and mean excess ratio + 2 pp) and energy supplied by ultra-processed food increased (+4 pp). Shifts in DSEC marginally explained some changes in dietary intakes (e.g. increased diet quality), while the changes that remained unexplained were of opposite sign, with decreased diet quality, lower fruits, tubers and fish intakes and higher energy provided by ultra-processed foods.
Conclusion:
Explained dietary changes were of opposite sign to nutrition transition conceptual framework, probably because unobserved drivers are in play, such as food price trends or supermarkets spread.
Dietary indexes measure the adherence of individuals to a set of nutritional recommendations. However, the health gains associated with adherence to various dietary indexes may vary. Our objective was to compare the magnitude of estimated avoided deaths by chronic diseases obtained by improving diet quality in the French population, measured by a variety of dietary indexes.
Design:
Simulation study based on observational data.
Setting:
Weighted data from a French population-based cohort study.
Participants:
In participants from the NutriNet-Santé cohort, we computed dietary scores reflecting the adherence to various recommendations (Medi-Lite, Healthy Diet Indicator (HDI), Programme National Nutrition Santé/National Nutrition and Health Program – Guidelines Score, Diet Quality Index (DQI), Alternative Healthy Eating Index (AHEI) and the modified Food Standards Agency nutrient profiling system dietary index (FSAm-NPS DI)). Quintiles of the food groups’ consumption and dietary intakes were used as input in a simulation model (Preventable Risk Integrated ModEl (PRIME)), yielding the number of delayed or avoided deaths in nutrition-related non-communicable diseases, comparing between very high or very low nutritional quality of the diet and medium nutritional quality.
Results:
A modification of dietary intakes from medium quality to very low quality (i.e. from the middle quintile to the quintile with the lowest nutritional quality) was associated with an increased number of deaths ranging from 3485 (95 % uncertainty interval (CI) 4002, 2987) for HDI and 3379 (95 % CI 3881, 2894) for FSAm-NPS DI to 838 (95 % CI 1163, 523) for Medi-Lite. Conversely, a modification of dietary intakes from medium quality to very high quality was associated with a decrease in the number of deaths ranging from 1995 (95 % CI 1676, 2299) for Probability of Adequate Nutrient intake diet, 1986 (95 % CI 1565, 2361) for DQI-International, 1931 (95 % CI 1499, 2316) for FSAm-NPS DI and 858 (95 % CI 499, 1205) for HDI.
Conclusions:
Our results provide some insights as the potential impact of following various dietary guidelines to reduce mortality from nutrition-related diseases.
We sought to develop a teaching pilot to help year 2 medical students meet the following learning outcomes: Develop a better understanding of patient and carer experiences of mental illness; Recognise and challenge unhelpful attitudes towards people with mental illness; Promote a broader understanding of cultural issues surrounding mental illness, including stigma and discrimination.
Method
337 medical students were invited to attend a lecture by author LQ, a documentary photographer who presented a narrative of his brother Justin's lived experience of schizophrenia (louisquail.com/big-brother-introduction). 197 students attended the session, which was recorded and made available online. Students were invited to enter a competition to win a signed copy of LQ's book, ‘Big Brother’ and asked to submit either a 500-word written reflective piece, or a creative work accompanied by a 200-word statement. 13 submissions were received, including paintings, drawings, collage, photography, and poetry, all of which were blind rated by authors SR and GB, based on originality and quality of reflection. Of the six shortlisted, three winning entries were chosen by author LQ.
Result
All reflections moved away from a technical understanding of schizophrenia, towards person-centred interpretations, with dominant themes of ‘stigma’, ‘disempowerment’, ‘understanding people as individuals’, ‘subjective experience of mental illness’, ‘inclusion’ and ‘healing power of nature’.
The three prize winners (authors GY, AK and KT) used different mediums: GY painted an osprey over a chaotic collage of disordered and stigmatizing words (the osprey representing empowerment and the “reservoir for wellbeing in nature”); AK's sonnet began as an ode to the chaos of Justin's experience, but the concluding lines reframed this struggle, conveying feelings of hope and beauty; and KT's self-portrait, produced with a slow shutter-speed photograph, powerfully conveyed a sense of disorientation and disturbance. She reflected on how the stigma of mental illness affects self-perception. The talk was well-attended, and reflections were of high quality. A limitation of this pilot was that only a small proportion of students completed the reflective assignment.
Conclusion
Innovative teaching strategies are needed to address negative attitudes towards mental illness and psychiatry, which are prevalent amongst the medical profession. This pilot provides a model for combining carer-led, reflective, and creative elements in undergraduate psychiatry teaching, with the aim of challenging stigma. This model will be evaluated in a further study involving fifth year medical students, which will use a validated scale to measure change in students’ attitudes towards mental illness and psychiatry.
Advice on replacing unhealthy foods with healthier alternatives within the same food category may be more acceptable and might ease the transition towards a healthy diet. Here, we studied the potential impact of substitutions within the pizza category on the risk of type 2 diabetes (T2D). The study sample consisted of 2510 adults from the INCA2 French national survey. Based on their nutritional characteristics, the 353 pizzas marketed in France were grouped into 100 clusters that were used to run various scenarios of pizza substitutions, which were either isoenergetic (IE) or non-isoenergetic (NIE). We then used a model structurally similar to the Preventable Risk Integrated ModEl to assess the expected rate of change in risk of T2D. Pizzas characterised by a low energy, high vegetable content and whole grain dough were associated with a greater reduction in the risk of T2D. The rates of change in risk of T2D were markedly stronger in men and for NIE substitutions. When the rates of change were estimated in the subsample of pizza consumers, replacing the observed pizzas with the best pizza resulted in a T2D risk reduction of −6·7 % (–8·4 %; −4·9 %, IE) and −8·9 % (–11·2 %; −6·3 %, NIE), assuming that this is their usual diets. The greatest risk reduction induced by an IE substitution of the observed pizza with a mixed dish was similar to that observed with the best pizzas. Overall, this modelling study suggests that healthy swaps within a category can effectively supplement broader dietary changes towards a healthier diet.
Competition from weeds is one of the major biophysical constraints to rice (Oryza spp.) production in sub-Saharan Africa. Smallholder rice farmers require efficient, affordable and labour-saving weed management technologies. Mechanical weeders have shown to fit this profile. Several mechanical weeder types exist but little is known about locally specific differences in performance and farmer preference between these types. Three to six different weeder types were evaluated at 10 different sites across seven countries – i.e., Benin, Burkina Faso, Côte d'Ivoire, Ghana, Nigeria, Rwanda and Togo. A total of 310 farmers (173 male, 137 female) tested the weeders, scored them for their preference, and compared them with their own weed management practices. In a follow-up study, 186 farmers from Benin and Nigeria received the ring hoe, which was the most preferred in these two countries, to use it during the entire crop growing season. Farmers were surveyed on their experiences. The probability of the ring hoe having the highest score among the tested weeders was 71%. The probability of farmers’ preference of the ring hoe over their usual practices – i.e., herbicide, traditional hoe and hand weeding – was 52, 95 and 91%, respectively. The preference of this weeder was not related to gender, years of experience with rice cultivation, rice field size, weed infestation level, water status or soil texture. In the follow-up study, 80% of farmers who used the ring hoe indicated that weeding time was reduced by at least 31%. Of the farmers testing the ring hoe in the follow-up study, 35% used it also for other crops such as vegetables, maize, sorghum, cassava and millet. These results suggest that the ring hoe offers a gender-neutral solution for reducing labour for weeding in rice as well as other crops and that it is compatible with a wide range of environments. The implications of our findings and challenges for out-scaling of mechanical weeders are discussed.
Across the globe, the implementation of quality improvement science and collaborative learning has positively affected the care and outcomes for children born with CHD. These efforts have advanced the collective expertise and performance of inter-professional healthcare teams. In this review, we highlight selected quality improvement initiatives and strategies impacting the field of cardiovascular care and describe implications for future practice and research. The continued leveraging of technology, commitment to data transparency, focus on team-based practice, and recognition of cultural norms and preferences ensure the success of sustainable models of global collaboration.
Regulatory impact analyses (RIAs) weigh the benefits of regulations against the burdens they impose and are invaluable tools for informing decision makers. We offer 10 tips for nonspecialist policymakers and interested stakeholders who will be reading RIAs as consumers.
1. Core problem: Determine whether the RIA identifies the core problem (compelling public need) the regulation is intended to address.
2. Alternatives: Look for an objective, policy-neutral evaluation of the relative merits of reasonable alternatives.
3. Baseline: Check whether the RIA presents a reasonable “counterfactual” against which benefits and costs are measured.
4. Increments: Evaluate whether totals and averages obscure relevant distinctions and trade-offs.
5. Uncertainty: Recognize that all estimates involve uncertainty, and ask what effect key assumptions, data, and models have on those estimates.
6. Transparency: Look for transparency and objectivity of analytical inputs.
7. Benefits: Examine how projected benefits relate to stated objectives.
8. Costs: Understand what costs are included.
9. Distribution: Consider how benefits and costs are distributed.
10. Symmetrical treatment: Ensure that benefits and costs are presented symmetrically.
Eemian lake deposits in Grande Pile and Ribains, France, correlate with marine isotope substages (MIS) 5e and 5d as delimited in two pollen-bearing deep-sea cores off Portugal. The Eemian forests in France lasted for approximately 20 millennia, from at least 126,000 to ca. 107,000 yr B.P. Oscillatory climate deteriorations began about 115,000 yr ago. An intense cold spell affected the region approximately 110,000 yr ago.
The last interglacial, commonly understood as an interval with climate as warm or warmer than today, is represented by marine isotope stage (MIS) 5e, which is a proxy record of low global ice volume and high sea level. It is arbitrarily dated to begin at approximately 130,000 yr B.P. and end at 116,000 yr B.P. with the onset of the early glacial unit MIS 5d. The age of the stage is determined by correlation to uranium–thorium dates of raised coral reefs. The most detailed proxy record of interglacial climate is found in the Vostok ice core where the temperature reached current levels 132,000 yr ago and continued rising for another two millennia. Approximately 127,000 yr ago the Eemian mixed forests were established in Europe. They developed through a characteristic succession of tree species, probably surviving well into the early glacial stage in southern parts of Europe. After ca. 115,000 yr ago, open vegetation replaced forests in northwestern Europe and the proportion of conifers increased significantly farther south. Air temperature at Vostok dropped sharply. Pulses of cold water affected the northern North Atlantic already in late MIS 5e, but the central North Atlantic remained warm throughout most of MIS 5d. Model results show that the sea surface in the eastern tropical Pacific warmed when the ice grew and sea level dropped. The essentially interglacial conditions in southwestern Europe remained unaffected by ice buildup until late MIS 5d when the forests disappeared abruptly and cold water invaded the central North Atlantic ca. 107,000 yr ago.
Although diffuse knapweed, kochia, and Russian thistle are important tumbleweeds of the western United States, environmental factors contributing to their dispersal are not well understood. Bolting rosettes of these species were transplanted to pots and reared in a common garden to determine the affect of postsenescence water on stem strength. There were no differences in stem strength among three water treatments for Russian thistle. Kochia, under moderate water treatment, required more than twice the force to break compared to plants under the zero and high water treatments. In contrast, diffuse knapweed plants under zero water treatment required four to six times greater force to break compared to plants under the moderate and high water treatments. There was a strong difference in diffuse knapweed stem strength between field collection sites that corresponded to observed differences in proportion of plants tumbling. A wind tunnel was used to develop a conversion factor between force and wind velocity. Wind velocities necessary to break diffuse knapweed stems ranged from 16 to 37 m/s (36 to 77 mph).
Several studies demonstrating that central line–associated bloodstream infections (CLABSIs) are preventable prompted a national initiative to reduce the incidence of these infections.
Methods.
We conducted a collaborative cohort study to evaluate the impact of the national “On the CUSP: Stop BSI” program on CLABSI rates among participating adult intensive care units (ICUs). The program goal was to achieve a unit-level mean CLABSI rate of less than 1 case per 1,000 catheter-days using standardized definitions from the National Healthcare Safety Network. Multilevel Poisson regression modeling compared infection rates before, during, and up to 18 months after the intervention was implemented.
Results.
A total of 1,071 ICUs from 44 states, the District of Columbia, and Puerto Rico, reporting 27,153 ICU-months and 4,454,324 catheter-days of data, were included in the analysis. The overall mean CLABSI rate significantly decreased from 1.96 cases per 1,000 catheter-days at baseline to 1.15 at 16–18 months after implementation. CLABSI rates decreased during all observation periods compared with baseline, with adjusted incidence rate ratios steadily decreasing to 0.57 (95% confidence intervals, 0.50–0.65) at 16–18 months after implementation.
Conclusion.
Coincident with the implementation of the national “On the CUSP: Stop BSI” program was a significant and sustained decrease in CLABSIs among a large and diverse cohort of ICUs, demonstrating an overall 43% decrease and suggesting the majority of ICUs in the United States can achieve additional reductions in CLABSI rates.