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Tropical Small Island Developing States (SIDS), such as those in the Caribbean, are among the most vulnerable to the impacts of climate change, most notably sea-level rise. The current sea-level rise in the Caribbean is 3.40 ± 0.3 mm/year (1993–2019), which is similar to the 3.25 ± 0.4 mm/year global mean sea-level (GMSL) rise (1993–2018). Throughout the year, Caribbean seasonal sea-level variability is found to respond to sea surface temperature variability. Over the past few decades, the trend in Caribbean Sea-level rise is also found to be variable. Satellite altimetry and steric sea-level records of the Caribbean region reveal a shift in the late 2003-early 2004, which separates two distinct periods of sea-level rise. Thermal expansion dominates the sea-level trend from 1993–2003. Following this period, there is an increased trend in sea-level rise, with a dominance of mass changes from 2004–2019, as confirmed by GRACE data. During this period, the sea-level trend is 6.15 ± 0.5 mm/year, which is 67% faster than the most recent estimates of global mean sea-level rise provided by the Intergovernmental Panel on Climate Change (3.69 ± 0.5 mm/year for the period 2006–2018). Despite its reduced importance, increasing temperatures contribute greatly to sea-level rise in the Caribbean region through thermal expansion of ocean water, hence there is a need to limit the current trend of global warming.

The warm and saline Atlantic Water has long been recognized as being subjected to substantial heat loss during its transit towards the polar regions. In particular, the Lofoten Basin, a subpolar sea with energetic eddy activity and strong air-sea interactions, plays a crucial role in the transformation of Atlantic Water. Vertical heat transport at submesoscales (0.1-10 km) in the Lofoten Basin is potentially a key link in the heat transfer to the atmosphere. Here, based on multi-year Seaglider observations augmented by satellite altimeters, radiometers, and high-resolution numerical model results, we evaluate the oceanic vertical heat transport in the Lofoten Basin and demonstrate how geostrophic strain enhances heat transport. The enhancement is found to be associated with submesoscale ageostrophic motions along the mesoscale eddy edges, occurring on spatial scales smaller than 10 km and below the mixed layer depth. These strain-induced submesoscale vertical motions transport heat from the ocean interior to the surface, leading to a 0.4 °C increase in sea surface temperature and the formation of “warm ring” structures in both cyclones and anticyclones. The dominant role of submesoscale heat transport likely represents the primary mechanism for substantial heat loss from Atlantic Water in the Lofoten Basin. The authors use data from underwater gliders, satellites and numerical simulations and show that submesoscale motions at ocean eddy edges pump heat upward, forming “warm rings” and a ~ 0.4 °C warming in the Lofoten Basin—a key pathway for Atlantic water heat loss.

Studies of the global sea-level budget (SLB) and the global ocean-mass budget (OMB) are essential to assess the reliability of our knowledge of sea-level change and its contributors. Here we present datasets for times series of the SLB and OMB elements developed in the framework of ESA's Climate Change Initiative. We use these datasets to assess the SLB and the OMB simultaneously, utilising a consistent framework of uncertainty characterisation. The time series, given at monthly sampling and available at https://doi.org/10.5285/17c2ce31784048de93996275ee976fff (Horwath et al., 2021), include global mean sea-level (GMSL) anomalies from satellite altimetry, the global mean steric component from Argo drifter data with incorporation of sea surface temperature data, the ocean-mass component from Gravity Recovery and Climate Experiment (GRACE) satellite gravimetry, the contribution from global glacier mass changes assessed by a global glacier model, the contribution from Greenland Ice Sheet and Antarctic Ice Sheet mass changes assessed by satellite radar altimetry and by GRACE, and the contribution from land water storage anomalies assessed by the global hydrological model WaterGAP (Water Global Assessment and Prognosis). Over the period January 1993–December 2016 (P1, covered by the satellite altimetry records), the mean rate (linear trend) of GMSL is 3.05 ± 0.24 mm yr−1. The steric component is 1.15 ± 0.12 mm yr−1 (38 % of the GMSL trend), and the mass component is 1.75 ± 0.12 mm yr−1 (57 %). The mass component includes 0.64  ± 0.03 mm yr−1 (21 % of the GMSL trend) from glaciers outside Greenland and Antarctica, 0.60 ± 0.04 mm yr−1 (20 %) from Greenland, 0.19 ± 0.04 mm yr−1 (6 %) from Antarctica, and 0.32 ± 0.10 mm yr−1 (10 %) from changes of land water storage. In the period January 2003–August 2016 (P2, covered by GRACE and the Argo drifter system), GMSL rise is higher than in P1 at 3.64 ± 0.26 mm yr−1. This is due to an increase of the mass contributions, now about 2.40 ± 0.13 mm yr−1 (66 % of the GMSL trend), with the largest increase contributed from Greenland, while the steric contribution remained similar at 1.19 ± 0.17 mm yr−1 (now 33 %). The SLB of linear trends is closed for P1 and P2; that is, the GMSL trend agrees with the sum of the steric and mass components within their combined uncertainties. The OMB, which can be evaluated only for P2, shows that our preferred GRACE-based estimate of the ocean-mass trend agrees with the sum of mass contributions within 1.5 times or 0.8 times the combined 1σ uncertainties, depending on the way of assessing the mass contributions. Combined uncertainties (1σ) of the elements involved in the budgets are between 0.29 and 0.42 mm yr−1, on the order of 10 % of GMSL rise. Interannual variations that overlie the long-term trends are coherently represented by the elements of the SLB and the OMB. Even at the level of monthly anomalies the budgets are closed within uncertainties, while also indicating possible origins of remaining misclosures.

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by poor response to standard therapies and therefore unfavorable clinical outcomes. Better understanding of TNBC and new therapeutic strategies are urgently needed. ROR nuclear receptors are multifunctional transcription factors with important roles in circadian pathways and other processes including immunity and tumorigenesis. Nobiletin (NOB) is a natural compound known to display anticancer effects, and our previous studies showed that NOB activates RORs to enhance circadian rhythms and promote physiological fitness in mice. Here, we identified several TNBC cell lines being sensitive to NOB, by itself or in combination. Cell and xenograft experiments showed that NOB significantly inhibited TNBC cell proliferation and motility in vitro and in vivo. ROR loss- and gain-of-function studies showed concordant effects of the NOB–ROR axis on MDA-MB-231 cell growth. Mechanistically, we found that NOB activates ROR binding to the ROR response elements (RRE) of the IκBα promoter, and NOB strongly inhibited p65 nuclear translocation. Consistent with transcriptomic analysis indicating cancer and NF-κB signaling as major pathways altered by NOB, p65-inducible expression abolished NOB effects, illustrating a requisite role of NF-κB suppression mediating the anti-TNBC effect of NOB. Finally, in vivo mouse xenograft studies showed that NOB enhanced the antitumor efficacy in mammary fat pad implanted TNBC, as a single agent or in combination with the chemotherapy agent Docetaxel. Together, our study highlights an anti-TNBC mechanism of ROR-NOB via suppression of NF-κB signaling, suggesting novel preventive and chemotherapeutic strategies against this devastating disease.

Introduction Healthcare provider burnout is highly prevalent and has negative consequences. However, many healthcare workers in LMICs, including Nepal, rarely recognize or ameliorate it. This problem is worse in rural settings. Competency-focused interventions that are developed using theoretical frameworks can address this gap. Methods We used Kern’s framework of curriculum development to create, refine, and assess a theory-driven intervention tailored to the needs and constraints of rural healthcare workers in Nepal. During the first phase, we conducted a targeted needs assessment using an online survey among nine rural primary care physicians working in Charikot Hospital. We then developed learning objectives for knowledge, attitude, and skills domains based on the World Health Organization (WHO) definition of burnout. Then, we created animated educational videos designed to meet the learning objectives. We then implemented the educational intervention with rural physicians and assessed their knowledge, attitudes, and feedback. During the second phase, we further developed the intervention based on findings from the first phase and assessed acceptability, feasibility, and preliminary impact using pre- and post-intervention questionnaires and key informant interviews. Results In the first phase, nine physicians participated in the targeted needs assessment, and eight responded to the post-intervention assessment. In the second phase, 18 attendees completed the pre-intervention burnout assessment, and 16 completed both the pre-test and post-test questionnaires. On the pre-test, correct answers across questions ranged from 31–88%, while on the post-test, participants responded correctly 88–100% of the time. Related-samples Wilcoxon signed-rank test showed a statistically significant difference ( P  = 0.007) in the post-test scores on the knowledge domain. Qualitative results showed burnout as an unrecognized and unreported issue, and its drivers included stigma and feelings of helplessness. Participants praised the interventions and reported that they translated learned skills into practice. Conclusion In this proof-of-concept study, we found that educational interventions developed using a theory-driven framework to meet the unique needs of rural healthcare workers are acceptable and feasible. Future studies can test the intervention impact in well-powered trials to support scale-up efforts to identify and address burnout.

Cuprous oxide (Cu2O) is a p-type semiconductor with high optical absorption and a direct bandgap of about 2.1 eV, making it an attractive material for photovoltaic applications. For a high-performance photovoltaic device, the formation of low-resistivity contacts on Cu2O thin films is a prerequisite, which can be achieved by, for instance, nitrogen doping of Cu2O in order to increase the carrier concentration. In this work, nitrogen-doped p-type Cu2O thin films were prepared on quartz substrates by magnetron sputter deposition. By adding N2 gas during the deposition process, a nitrogen concentration of up to 2.3 × 1021 atoms/cm3 in the Cu2O thin films was achieved, as determined from secondary ion mass spectroscopy measurements. The effect of nitrogen doping on the structural, optical, and electrical properties of the Cu2O thin films was investigated. X-ray diffraction measurements suggest a preservation of the Cu2O phase for the nitrogen doped thin films, whereas spectrophotometric measurements show that the optical properties were not significantly altered by incorporation of nitrogen into the Cu2O matrix. A significant conductivity enhancement was achieved for the nitrogen-doped Cu2O thin films, based on Hall effect measurements, i.e., the hole concentration was increased from 4 × 1015 to 3 × 1019 cm−3 and the resistivity was reduced from 190 to 1.9 Ω⋅cm by adding nitrogen to the Cu2O thin films.