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Summary: Background: In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period. Methods: Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time. Findings: A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn’s disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 105 person-years, respectively. The incidence of CD increased from 5.1/105 in 1988–1990 to 7.9/105 in 2015–2017 (annual percent change (APC): +1.9%, p

Abstract Every austral spring when Antarctic sea ice melts, favorable growing conditions lead to an intense phytoplankton bloom, which supports much of the local marine ecosystem. Recent studies have found that Antarctic sea ice is predictable several years in advance, suggesting that the spring bloom might exhibit similar predictability. Using a suite of perfect model predictability experiments, we find that November net primary production (NPP) is potentially predictable 7 to 10 years in advance in many Southern Ocean regions. Sea ice extent predictability peaks in late winter, followed by absorbed shortwave radiation and NPP with a 2 to 3 months lag. This seasonal progression of predictability supports our hypothesis that sea ice and light limitation control the inherent predictability of the spring bloom. Our results suggest skillful interannual predictions of NPP may be achievable, with implications for managing fisheries and the marine ecosystem, and guiding conservation policy in the Southern Ocean.

Extreme events can severely impact marine organisms and ecosystems. Of particular concern are multivariate compound events, namely when conditions are simultaneously extreme for multiple ocean ecosystem stressors. In 2013–2015 for example, an extensive marine heatwave (MHW), known as the Blob, co-occurred locally with extremely low net primary productivity (NPPX) and negatively impacted marine life in the northeast Pacific. Yet, little is known about the characteristics and drivers of such multivariate compound MHW–NPPX events. Using five different satellite-derived net primary productivity (NPP) estimates and large-ensemble-simulation output of two widely used and comprehensive Earth system models, the Geophysical Fluid Dynamics Laboratory (GFDL) ESM2M-LE and Community Earth System Model version 2 (CESM2-LE), we assess the present-day distribution of compound MHW–NPPX events and investigate their potential drivers on the global scale. The satellite-based estimates and both models reveal hotspots of frequent compound events in the center of the equatorial Pacific and in the subtropical Indian Ocean, where their occurrence is at least 3 times higher (more than 10 d yr−1) than if MHWs (temperature above the seasonally varying 90th-percentile threshold) and NPPX events (NPP below the seasonally varying 10th-percentile threshold) were to occur independently. However, the models show disparities in the northern high latitudes, where compound events are rare in the satellite-based estimates and GFDL ESM2M-LE (less than 3 d yr−1) but relatively frequent in CESM2-LE. In the Southern Ocean south of 60∘ S, low agreement between the observation-based estimates makes it difficult to determine which of the two models better simulates MHW–NPPX events. The frequency patterns can be explained by the drivers of compound events, which vary among the two models and phytoplankton types. In the low latitudes, MHWs are associated with enhanced nutrient limitation on phytoplankton growth, which results in frequent compound MHW–NPPX events in both models. In the high latitudes, NPPX events in GFDL ESM2M-LE are driven by enhanced light limitation, which rarely co-occurs with MHWs, resulting in rare compound events. In contrast, in CESM2-LE, NPPX events in the high latitudes are driven by reduced nutrient supply that often co-occurs with MHWs, moderates phytoplankton growth, and causes biomass to decrease. Compound MHW–NPPX events are associated with a relative shift towards larger phytoplankton in most regions, except in the eastern equatorial Pacific in both models, as well as in the northern high latitudes and between 35 and 50∘ S in CESM2-LE, where the models suggest a shift towards smaller phytoplankton, with potential repercussions on marine ecosystems. Overall, our analysis reveals that the likelihood of compound MHW–NPPX events is contingent on model representation of the factors limiting phytoplankton production. This identifies an important need for improved process understanding in Earth system models used for predicting and projecting compound MHW–NPPX events and their impacts.

As extreme event attribution (EEA) matures, explaining the impacts of extreme events has risen to be a key focus for attribution scientists. Studies of this type usually assess the contribution of anthropogenic climate change to observed impacts. Other scientific communities have developed tools to assess how human activities influence impacts of extreme weather events on ecosystems and societies. For example, the disaster risk reduction (DRR) community analyses how the structure of human societies affects exposure, vulnerability, and ultimately the impacts of extreme weather events, with less attention to the role of anthropogenic climate change. In this perspective, we argue that adapting current practice in EEA to also consider other causal factors in attribution of extreme weather impacts would provide richer and more comprehensive insight into the causes of disasters. To this end, we propose a framework for EEA that would generate a more complete picture of human influences on impacts and bridge the gap between the EEA and DRR communities. We provide illustrations for five case studies: the 2021–2022 Kenyan drought; the 2013–2015 marine heatwave in the northeast Pacific; the 2017 forest fires in Portugal; Acqua Alta (flooding) events in Venice and evaluation of the efficiency of the Experimental Electromechanical Module, an ensemble of mobile barriers that can be activated to mitigate the influx of seawater in the city; and California droughts and the Forecast Informed Reservoir Operations system as an adaptation strategy.

Extreme events in the ocean severely impact marine organisms and ecosystems. Of particular concern are compound events, i.e., when conditions are extreme for multiple potential ocean ecosystem stressors such as temperature and chlorophyll. Yet, little is known about the occurrence, intensity, and duration of such compound high-temperature (a.k.a. marine heatwaves – MHWs) and low-chlorophyll (LChl) extreme events, whether their distributions have changed in the past decades, and what the potential drivers are. Here we use satellite-based sea surface temperature and chlorophyll concentration estimates to provide a first assessment of such compound extreme events. We reveal hotspots of compound MHW and LChl events in the equatorial Pacific, along the boundaries of the subtropical gyres, in the northern Indian Ocean, and around Antarctica. In these regions, compound events that typically last 1 week occur 3 to 7 times more often than expected under the assumption of independence between MHWs and LChl events. The occurrence of compound MHW and LChl events varies on seasonal to interannual timescales. At the seasonal timescale, most compound events occur in summer in both hemispheres. At the interannual timescale, the frequency of compound MHW and LChl events is strongly modulated by large-scale modes of natural climate variability such as the El Niño–Southern Oscillation, whose positive phase is associated with increased compound event occurrence in the eastern equatorial Pacific and in the Indian Ocean by a factor of up to 4. Our results provide a first understanding of where, when, and why compound MHW and LChl events occur. Further studies are needed to identify the exact physical and biological drivers of these potentially harmful events in the ocean and their evolution under global warming.

Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising microcephaly, craniofacial anomalies, hearing loss, dysmorphic features, and, in some cases, esophageal atresia. Haploinsufficiency of a spliceosomal GTPase, U5-116 kDa/EFTUD2, is responsible. Here, we review the molecular basis of MFDM in the 69 individuals described to date, and report mutations in 38 new individuals, bringing the total number of reported individuals to 107 individuals from 94 kindreds. Pathogenic EFTUD2 variants comprise 76 distinct mutations and seven microdeletions. Among point mutations, missense substitutions are infrequent (14 out of 76; 18%) relative to stop-gain (29 out of 76; 38%), and splicing (33 out of 76; 43%) mutations. Where known, mutation origin was de novo in 48 out of 64 individuals (75%), dominantly inherited in 12 out of 64 (19%), and due to proven germline mosaicism in four out of 64 (6%). Highly penetrant clinical features include, microcephaly, first and second arch craniofacial malformations, and hearing loss; esophageal atresia is present in an estimated ∼27%. Microcephaly is virtually universal in childhood, with some adults exhibiting late "catch-up" growth and normocephaly at maturity. Occasionally reported anomalies, include vestibular and ossicular malformations, reduced mouth opening, atrophy of cerebral white matter, structural brain malformations, and epibulbar dermoid. All reported EFTUD2 mutations can be found in the EFTUD2 mutation database (http://databases.lovd.nl/shared/genes/EFTUD2).

Maintenance of DNA integrity is crucial for all cell types, but neurons are particularly sensitive to mutations in DNA repair genes, which lead to both abnormal development and neurodegeneration. We describe a previously unknown autosomal recessive disease characterized by microcephaly, early-onset, intractable seizures and developmental delay (denoted MCSZ). Using genome-wide linkage analysis in consanguineous families, we mapped the disease locus to chromosome 19q13.33 and identified multiple mutations in PNKP (polynucleotide kinase 3'-phosphatase) that result in severe neurological disease; in contrast, a splicing mutation is associated with more moderate symptoms. Unexpectedly, although the cells of individuals carrying this mutation are sensitive to radiation and other DNA-damaging agents, no such individual has yet developed cancer or immunodeficiency. Unlike other DNA repair defects that affect humans, PNKP mutations universally cause severe seizures. The neurological abnormalities in individuals with MCSZ may reflect a role for PNKP in several DNA repair pathways.

This paper seeks to contribute to the growing literature on ‘soft power’ by focusing on East Asia as a region gaining in political and economic significance; equally, we highlight the role sports mega-events play in the region’s most powerful states’ soft power strategies. For the purpose of this paper, we focus on South Korea’s soft power strategy and how the hosting of major sporting events has become a central part of this. We introduce both a novel tripartite approach to the study of the motives behind hosting sports mega-events, along with new, empirical data on the chosen case of South Korea. Our findings strengthen the notion that an explanation of why states seek to host major sports events can be better understood by considering the domestic, regional and international dimensions to capture the complexities behind such decisions.

Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations.