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In October 2023, the Baltic Sea coasts of Germany and Denmark experienced a severe storm surge, predominantly impacting the German state of Schleswig-Holstein and parts of southern Denmark. The surge led to extensive flooding in cities like Flensburg and Schleswig, causing the breaching of at least six (regional) dikes and causing over EUR 200 million in damages in Schleswig-Holstein. By chance, the peak water levels of this storm surge aligned well with those of recent hydrodynamic flood modelling studies of the region. This rare coincidence offers crucial insights for our understanding of flooding impacts, flood management, and modelling. By comparing those studies to the real-world example using extensive media reports, we aim to extract key insights and identify gaps to be tackled in order to improve flood risk modelling in the Baltic Sea region and beyond. [ABSTRACT FROM AUTHOR]

Aims Cardiac implantable electronic device (CIED) infections are a burden to hospitals and costly for healthcare systems. Chronic kidney disease (CKD) increases the risk of CIED infections, but its differential impact on healthcare utilization, costs, and outcomes is not known. Methods and results This retrospective analysis used de-identified Medicare Fee-for-Service claims to identify patients implanted with a CIED from July 2016 to December 2020. Outcomes were defined as hospital days and costs within 12 months post-implant, post-infection CKD progression, and mortality. Generalized linear models were used to calculate results by CKD and infection status while controlling for other comorbidities, with differences between cohorts representing the incremental effect associated with CKD. A total of 584 543 patients had a CIED implant, of which 26% had CKD and 1.4% had a device infection. The average total days in hospital for infected patients was 23.5 days with CKD vs. 14.5 days (P < 0.001) without. The average cost of infection was $121 756 with CKD vs. $55 366 without (P < 0.001), leading to an incremental cost associated with CKD of $66 390. Infected patients with CKD were more likely to have septicaemia or severe sepsis than those without CKD (11.0 vs. 4.6%, P < 0.001). After infection, CKD patients were more likely to experience CKD progression (hazard ratio 1.26, P < 0.001) and mortality (hazard ratio 1.89, P < 0.001). Conclusion Cardiac implantable electronic device infection in patients with CKD was associated with more healthcare utilization, higher cost, greater disease progression, and greater mortality compared to patients without CKD. [ABSTRACT FROM AUTHOR]

In October 2023, Germany and Denmark's Baltic Sea coasts experienced a severe storm surge, predominantly impacting the German state of Schleswig-Holstein and parts of southern Denmark. The surge led to extensive flooding in cities like Flensburg and Schleswig, causing the breaching of at least seven (regional) dikes and causing over 200 million Euros in damages in Schleswig-Holstein. This surge offers crucial insights for our understanding of flooding impacts, flood management and modelling. By analyzing recent studies from the region and extensive media reports, we aim to extract key insights and propose strategies for improving flood risk modelling in the Baltic Sea region and beyond. [ABSTRACT FROM AUTHOR]

PurposeTargeting of the HER2 protein in human breast cancer represents a major advance in oncology but relies on measurements of total HER2 protein and not HER2 signaling network activation. We used reverse-phase protein microarrays (RPMA) to measure total and phosphorylated HER2 in the context of HER family signaling to understand correlations between phosphorylated and total levels of HER2 and downstream signaling activity.Experimental designThree independent study sets, comprising a total of 415 individual patient samples from flash-frozen core biopsy samples and formalin-fixed and paraffin-embedded (FFPE) surgical and core samples, were analyzed via RPMA. The phosphorylation and total levels of the HER receptor family proteins and downstream signaling molecules were measured in laser capture microdissected (LCM) enriched tumor epithelium from 127 frozen pretreatment core biopsy samples and whole-tissue lysates from 288 FFPE samples and these results were compared with FISH and immunohistochemistry (IHC).ResultsRPMA measurements of total HER2 were highly concordant (>90% all sets) with FISH and/or IHC data, as was phosphorylation of HER2 in the FISH/IHC(+) population. Phosphorylation analysis of HER family signaling identified HER2 activation in some FISH/IHC(-) tumors and, identical to that seen with FISH/IHC(+) tumors, the HER2 activation was concordant with EGF receptor (EGFR) and HER3 phosphorylation and downstream signaling endpoint activation.ConclusionsMolecular profiling of HER2 signaling of a large cohort of human breast cancer specimens using a quantitative and sensitive functional pathway activation mapping technique reveals IHC(-)/FISH(-)/pHER2(+) tumors with HER2 pathway activation independent of total HER2 levels and functional signaling through HER3 and EGFR.

The response of coastal wetlands to sea-level rise during the twenty-first century remains uncertain. Global-scale projections suggest that between 20 and 90 per cent (for low and high sea-level rise scenarios, respectively) of the present-day coastal wetland area will be lost, which will in turn result in the loss of biodiversity and highly valued ecosystem services.sup.1-3. These projections do not necessarily take into account all essential geomorphological.sup.4-7 and socio-economic system feedbacks.sup.8. Here we present an integrated global modelling approach that considers both the ability of coastal wetlands to build up vertically by sediment accretion, and the accommodation space, namely, the vertical and lateral space available for fine sediments to accumulate and be colonized by wetland vegetation. We use this approach to assess global-scale changes in coastal wetland area in response to global sea-level rise and anthropogenic coastal occupation during the twenty-first century. On the basis of our simulations, we find that, globally, rather than losses, wetland gains of up to 60 per cent of the current area are possible, if more than 37 per cent (our upper estimate for current accommodation space) of coastal wetlands have sufficient accommodation space, and sediment supply remains at present levels. In contrast to previous studies.sup.1-3, we project that until 2100, the loss of global coastal wetland area will range between 0 and 30 per cent, assuming no further accommodation space in addition to current levels. Our simulations suggest that the resilience of global wetlands is primarily driven by the availability of accommodation space, which is strongly influenced by the building of anthropogenic infrastructure in the coastal zone and such infrastructure is expected to change over the twenty-first century. Rather than being an inevitable consequence of global sea-level rise, our findings indicate that large-scale loss of coastal wetlands might be avoidable, if sufficient additional accommodation space can be created through careful nature-based adaptation solutions to coastal management.A global modelling approach shows that in response to rises in global sea level, gains of up to 60% in coastal wetland areas are possible, if appropriate coastal management solutions are developed to help support wetland resilience., Author(s): Mark Schuerch [sup.1] [sup.2] , Tom Spencer [sup.2] , Stijn Temmerman [sup.3] , Matthew L. Kirwan [sup.4] , Claudia Wolff [sup.5] , Daniel Lincke [sup.6] , Chris J. McOwen [...]

Abstract Background The World Health Organization recommends that national malaria programmes universally distribute long-lasting insecticide-treated bed nets (LLINs). LLINs provide effective insecticide protection for at least three years while conventional nets must be retreated every 6-12 months. LLINs may also promise longer physical durability (lifespan), but at a higher unit price. No prospective data currently available is sufficient to calculate the comparative cost effectiveness of different net types. We thus constructed a model to explore the cost effectiveness of LLINs, asking how a longer lifespan affects the relative cost effectiveness of nets, and if, when and why LLINs might be preferred to conventional insecticide-treated nets. An innovation of our model is that we also considered the replenishment need i.e. loss of nets over time. Methods We modelled the choice of net over a 10-year period to facilitate the comparison of nets with different lifespan (and/or price) and replenishment need over time. Our base case represents a large-scale programme which achieves high coverage and usage throughout the population by distributing either LLINs or conventional nets through existing health services, and retreats a large proportion of conventional nets regularly at low cost. We identified the determinants of bed net programme cost effectiveness and parameter values for usage rate, delivery and retreatment cost from the literature. One-way sensitivity analysis was conducted to explicitly compare the differential effect of changing parameters such as price, lifespan, usage and replenishment need. Results If conventional and long-lasting bed nets have the same physical lifespan (3 years), LLINs are more cost effective unless they are priced at more than USD 1.5 above the price of conventional nets. Because a longer lifespan brings delivery cost savings, each one year increase in lifespan can be accompanied by a USD 1 or more increase in price without the cheaper net (of the same type) becoming more cost effective. Distributing replenishment nets each year in addition to the replacement of all nets every 3-4 years increases the number of under-5 deaths averted by 5-14% at a cost of USD 17-25 per additional person protected per annum or USD 1080-1610 per additional under-5 death averted. Conclusions Our results support the World Health Organization recommendation to distribute only LLINs, while giving guidance on the price thresholds above which this recommendation will no longer hold. Programme planners should be willing to pay a premium for nets which have a longer physical lifespan, and if planners are willing to pay USD 1600 per under-5 death averted, investing in replenishment is cost effective.