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Improving our understanding of future ocean carbon uptake requires a nuanced understanding of the value of the annual ocean sink. Here, we combine an abatement cost-based approach and a climate damage-based approach to assess the value of the annual ocean sink. The former shows that the aggregate cost of national climate policies could increase by up to USD 80 billion if the ocean carbon sink weakens by 10 percent. As a complementary perspective, the damage-based approach shows that the annual ocean carbon sink contributes between USD 300 billion and USD 2,332 billion to countries’ inclusive wealth. Despite the conceptual appeal of the damage-based approach for its potential insights into regional wealth redistribution, uncertainties in national social cost of carbon estimates make it less reliable than the abatement cost-based approach, which in turn provides more reliable estimates for a fiscal cost assessment of improved monitoring services of the ocean carbon sink.

Improving our understanding of future ocean carbon uptake requires a nuanced understanding of the value of the annual ocean sink. Here, we combine an abatement cost-based approach and a climate damage-based approach to assess the value of the annual ocean sink. The former shows that the aggregate cost of national climate policies could increase by up to USD 80 billion if the ocean carbon sink weakens by 10 percent. As a complementary perspective, the damage-based approach shows that the annual ocean carbon sink contributes between USD 300 billion and USD 2,332 billion to countries’ inclusive wealth. Despite the conceptual appeal of the damage-based approach for its potential insights into regional wealth redistribution, uncertainties in national social cost of carbon estimates make it less reliable than the abatement cost-based approach, which in turn provides more reliable estimates for a fiscal cost assessment of improved monitoring services of the ocean carbon sink.

Improving our understanding of future ocean carbon uptake requires a nuanced understanding of the value of the annual ocean sink. Here, we combine an abatement cost-based approach and a climate damage-based approach to assess the value of the annual ocean sink. The former shows that the aggregate cost of national climate policies could increase by up to USD 80 billion if the ocean carbon sink weakens by 10 percent. As a complementary perspective, the damage-based approach shows that the annual ocean carbon sink contributes between USD 300 billion and USD 2,332 billion to countries’ inclusive wealth. Despite the conceptual appeal of the damage-based approach for its potential insights into regional wealth redistribution, uncertainties in national social cost of carbon estimates make it less reliable than the abatement cost-based approach, which in turn provides more reliable estimates for a fiscal cost assessment of improved monitoring services of the ocean carbon sink.

Currently, the ocean carbon sink annually removes about a third of anthropogenic fossil fuel and industrial CO2 emissions, reducing therefore climate change damages and CO2 abatement costs. While the land sinks have entered climate policies, the ocean sink has not—for good reasons since the former stores carbon within the boundaries of a state while the ocean removes carbon from the atmosphere rather in its property as a global common. However, the question remains what is the value of the ocean carbon sink and should it be differently attributed when comparing a coastal state with a large exclusive economic zone (EEZ) compared to landlocked state. Here, we demonstrate different approaches to value the ocean sink, comparing a climate-change damage-based approach with an abatement, market-based approach. We use a high-resolution carbon flux dataset (0.25x0.25 degree) to estimate the ocean carbon sink and source in coastal areas. We assign a net sink of 1.72 GtC proportional to countries with negative carbon fluxes in their EEZ. In our calculation the annual value of the global ocean sink ranges from 61.19 B USD (Std 31.80), equivalent to the 2021 GDP of Slovenia, to 1433 B USD (Std 94.30), equivalent to the 2021 GDP of Spain (World Bank data) for the abatement cost-based assessment approach (assuming full emission trading and low ambition levels in the national determined contribution) and for the climate-change damage-based assessment approach relying on an upper value of the social cost of carbon in our investigation. By breaking down the carbon sink by nations EEZ we estimate which countries are the largest donors of ocean carbon wealth and which countries would be affected the most if a weakening of the ocean sink would need to be compensated by higher emission reduction levels.

Currently, the ocean carbon sink annually removes about a third of anthropogenic fossil fuel and industrial CO2 emissions, reducing therefore climate change damages and CO2 abatement costs. While the land sinks have entered climate policies, the ocean sink has not—for good reasons since the former stores carbon within the boundaries of a state while the ocean removes carbon from the atmosphere rather in its property as a global common. However, the question remains what is the value of the ocean carbon sink and should it be differently attributed when comparing a coastal state with a large exclusive economic zone (EEZ) compared to landlocked state. Here, we demonstrate different approaches to value the ocean sink, comparing a climate-change damage-based approach with an abatement, market-based approach. We use a high-resolution carbon flux dataset (0.25x0.25 degree) to estimate the ocean carbon sink and source in coastal areas. We assign a net sink of 1.72 GtC proportional to countries with negative carbon fluxes in their EEZ. In our calculation the annual value of the global ocean sink ranges from 61.19 B USD (Std 31.80), equivalent to the 2021 GDP of Slovenia, to 1433 B USD (Std 94.30), equivalent to the 2021 GDP of Spain (World Bank data) for the abatement cost-based assessment approach (assuming full emission trading and low ambition levels in the national determined contribution) and for the climate-change damage-based assessment approach relying on an upper value of the social cost of carbon in our investigation. By breaking down the carbon sink by nations EEZ we estimate which countries are the largest donors of ocean carbon wealth and which countries would be affected the most if a weakening of the ocean sink would need to be compensated by higher emission reduction levels.

The ocean carbon sink annually removes about a third of anthropogenic CO2 emissions, reducing climate change damage and CO2 abatement costs. While land sinks have been integrated into climate policies, the ocean sink has not—for good reason, since the former stores carbon within the boundaries of a given country, while the latter removes carbon from the atmosphere as global commons. However, the question of the value of the oceanic carbon sink remains, and how it should be attributed when comparing a coastal country with a large exclusive economic zone (EEZ) to a landlocked country. Here, we demonstrate different approaches to valuing the ocean carbon sink, comparing a climate-change-damage-based approach with an abatement-based and market-based approach. We use a high-resolution carbon flux dataset (0.25x0.25 degrees) to estimate the oceanic carbon sinks and sources in coastal areas. We assign a net sink of 1.72 GtC proportional to countries with negative carbon fluxes in their EEZs. In our calculation, the annual value of the global ocean sink ranges from 66 B USD to 1432 B USD.

Currently, the ocean carbon sink annually removes about a third of anthropogenic fossil fuel and industrial CO2 emissions, reducing therefore climate change damages and CO2 abatement costs. While the land sinks have entered climate policies, the ocean sink has not—for good reasons since the former stores carbon within the boundaries of a state while the ocean removes carbon from the atmosphere rather in its property as a global common. However, the question remains what is the value of the ocean carbon sink and should it be differently attributed when comparing a coastal state with a large exclusive economic zone (EEZ) compared to landlocked state. Here, we demonstrate different approaches to value the ocean sink, comparing a climate-change damage-based approach with an abatement, market-based approach. We use a high-resolution carbon flux dataset (0.25x0.25 degree) to estimate the ocean carbon sink and source in coastal areas. We assign a net sink of 1.72 GtC proportional to countries with negative carbon fluxes in their EEZ. In our calculation the annual value of the global ocean sink ranges from 61.19 B USD (Std 31.80), equivalent to the 2021 GDP of Slovenia, to 1433 B USD (Std 94.30), equivalent to the 2021 GDP of Spain (World Bank data) for the abatement cost-based assessment approach (assuming full emission trading and low ambition levels in the national determined contribution) and for the climate-change damage-based assessment approach relying on an upper value of the social cost of carbon in our investigation. By breaking down the carbon sink by nations EEZ we estimate which countries are the largest donors of ocean carbon wealth and which countries would be affected the most if a weakening of the ocean sink would need to be compensated by higher emission reduction levels.

The ocean carbon sink annually removes about a third of anthropogenic CO2 emissions, reducing climate change damage and CO2 abatement costs. While land sinks have been integrated into climate policies, the ocean sink has not—for good reason, since the former stores carbon within the boundaries of a given country, while the latter removes carbon from the atmosphere as global commons. However, the question of the value of the oceanic carbon sink remains, and how it should be attributed when comparing a coastal country with a large exclusive economic zone (EEZ) to a landlocked country. Here, we demonstrate different approaches to valuing the ocean carbon sink, comparing a climate-change-damage-based approach with an abatement-based and market-based approach. We use a high-resolution carbon flux dataset (0.25x0.25 degrees) to estimate the oceanic carbon sinks and sources in coastal areas. We assign a net sink of 1.72 GtC proportional to countries with negative carbon fluxes in their EEZs. In our calculation, the annual value of the global ocean sink ranges from 66 B USD to 1432 B USD.

The ocean carbon sink annually removes about a third of anthropogenic CO2 emissions, reducing climate change damage and CO2 abatement costs. While land sinks have been integrated into climate policies, the ocean sink has not—for good reason, since the former stores carbon within the boundaries of a given country, while the latter removes carbon from the atmosphere as global commons. However, the question of the value of the oceanic carbon sink remains, and how it should be attributed when comparing a coastal country with a large exclusive economic zone (EEZ) to a landlocked country. Here, we demonstrate different approaches to valuing the ocean carbon sink, comparing a climate-change-damage-based approach with an abatement-based and market-based approach. We use a high-resolution carbon flux dataset (0.25x0.25 degrees) to estimate the oceanic carbon sinks and sources in coastal areas. We assign a net sink of 1.72 GtC proportional to countries with negative carbon fluxes in their EEZs. In our calculation, the annual value of the global ocean sink ranges from 66 B USD to 1432 B USD.

Carbon sequestration and storage in mangroves, salt marshes and seagrass meadows is an essential coastal ‘blue carbon’ ecosystem service for climate change mitigation. Here we offer a comprehensive, global and spatially explicit economic assessment of carbon sequestration and storage in three coastal ecosystem types at the global and national levels. We propose a new approach based on the country-specific social cost of carbon that allows us to calculate each country’s contribution to, and redistribution of, global blue carbon wealth. Globally, coastal ecosystems contribute a mean ± s.e.m. of US$190.67 ± 30 bn yr−1 to blue carbon wealth. The three countries generating the largest positive net blue wealth contribution for other countries are Australia, Indonesia and Cuba, with Australia alone generating a positive net benefit of US$22.8 ± 3.8 bn yr−1 for the rest of the world through coastal ecosystem carbon sequestration and storage in its territory.

Carbon sequestration and storage in mangroves, salt marshes and seagrass meadows is an essential coastal ‘blue carbon’ ecosystem service for climate change mitigation. Here we offer a comprehensive, global and spatially explicit economic assessment of carbon sequestration and storage in three coastal ecosystem types at the global and national levels. We propose a new approach based on the country-specific social cost of carbon that allows us to calculate each country’s contribution to, and redistribution of, global blue carbon wealth. Globally, coastal ecosystems contribute a mean ± s.e.m. of US$190.67 ± 30 bn yr−1 to blue carbon wealth. The three countries generating the largest positive net blue wealth contribution for other countries are Australia, Indonesia and Cuba, with Australia alone generating a positive net benefit of US$22.8 ± 3.8 bn yr−1 for the rest of the world through coastal ecosystem carbon sequestration and storage in its territory.

Carbon sequestration and storage in mangroves, salt marshes and seagrass meadows is an essential coastal ‘blue carbon’ ecosystem service for climate change mitigation. Here we offer a comprehensive, global and spatially explicit economic assessment of carbon sequestration and storage in three coastal ecosystem types at the global and national levels. We propose a new approach based on the country-specific social cost of carbon that allows us to calculate each country’s contribution to, and redistribution of, global blue carbon wealth. Globally, coastal ecosystems contribute a mean ± s.e.m. of US$190.67 ± 30 bn yr−1 to blue carbon wealth. The three countries generating the largest positive net blue wealth contribution for other countries are Australia, Indonesia and Cuba, with Australia alone generating a positive net benefit of US$22.8 ± 3.8 bn yr−1 for the rest of the world through coastal ecosystem carbon sequestration and storage in its territory.

Carbon sequestration and storage in mangroves, salt marshes and seagrass meadows is an essential coastal ‘blue carbon’ ecosystem service for climate change mitigation. Here we offer a comprehensive, global and spatially explicit economic assessment of carbon sequestration and storage in three coastal ecosystem types at the global and national levels. We propose a new approach based on the country-specific social cost of carbon that allows us to calculate each country’s contribution to, and redistribution of, global blue carbon wealth. Globally, coastal ecosystems contribute a mean ± s.e.m. of US$190.67 ± 30 bn yr−1 to blue carbon wealth. The three countries generating the largest positive net blue wealth contribution for other countries are Australia, Indonesia and Cuba, with Australia alone generating a positive net benefit of US$22.8 ± 3.8 bn yr−1 for the rest of the world through coastal ecosystem carbon sequestration and storage in its territory.

We introduce a novel approach to statistically assess the non-linear interaction of tide and non-tidal residual in order to quantify its contribution to extreme sea levels and hence its role in modulating coastal protection levels, globally. We demonstrate that extreme sea levels are up to 30% (or 70 cm) higher if non-linear interactions are not accounted for (e.g., by independently adding astronomical and non-astronomical components, as is often done in impact case studies). These overestimates are similar to recent sea-level rise projections to 2100 at some locations. Furthermore, we further find evidence for changes in this non-linear interaction over time, which has the potential for counteracting the increasing flood risk associated with sea-level rise and tidal and/or meteorological changes alone. Finally, we show how accounting for non-linearity in coastal impact assessment modulates coastal exposure, reducing recent estimates of global coastal flood costs by ~16%, and population affected by ~8%.

We introduce a novel approach to statistically assess the non-linear interaction of tide and non-tidal residual in order to quantify its contribution to extreme sea levels and hence its role in modulating coastal protection levels, globally. We demonstrate that extreme sea levels are up to 30% (or 70 cm) higher if non-linear interactions are not accounted for (e.g., by independently adding astronomical and non-astronomical components, as is often done in impact case studies). These overestimates are similar to recent sea-level rise projections to 2100 at some locations. Furthermore, we further find evidence for changes in this non-linear interaction over time, which has the potential for counteracting the increasing flood risk associated with sea-level rise and tidal and/or meteorological changes alone. Finally, we show how accounting for non-linearity in coastal impact assessment modulates coastal exposure, reducing recent estimates of global coastal flood costs by ~16%, and population affected by ~8%.

We have developed a new coastal database for the Mediterranean basin that is intended for coastal impact and adaptation assessment to sea-level rise and associated hazards on a regional scale. The data structure of the database relies on a linear representation of the coast with associated spatial assessment units. Using information on coastal morphology, human settlements and administrative boundaries, we have divided the Mediterranean coast into 13 900 coastal assessment units. To these units we have spatially attributed 160 parameters on the characteristics of the natural and socio-economic subsystems, such as extreme sea levels, vertical land movement and number of people exposed to sea-level rise and extreme sea levels. The database contains information on current conditions and on plausible future changes that are essential drivers for future impacts, such as sea-level rise rates and socio-economic development. Besides its intended use in risk and impact assessment, we anticipate that the Mediterranean Coastal Database (MCD) constitutes a useful source of information for a wide range of coastal applications., Peer Reviewed, Postprint (published version)

Bei neuen Ansätzen zur Behandlung von Tumorpatienten nimmt die umfassende Charakterisierung deregulierter Signalproteine im erkrankten Gewebe eine Schlüsselrolle ein. Damit lassen sich zum einen Zielstrukturen für effektivere Therapien entwickeln, zum anderen stellen abnormal aktivierte Signalmoleküle Biomarker dar, um Patienten für diese neuen Therapieoptionen auswählen zu können. In meiner Arbeit habe ich zunächst die Proteinextraktion aus klinischen Tumorproben (Formalin-fixierte Brustkrebsgewebe) optimiert. Durch den nachfolgenden Einsatz der Hochdurchsatztechnik des „Reverse Phase Protein Arrays“ konnten in den Tumorzelllysaten erstmals Therapie-relevante Markerproteine (u.a. HER2, uPA und PAI-1) und deren assoziierte Netzwerke quantitativ dargestellt werden. Die Ergebnisse dieser Arbeit liefern ein besseres Verständnis für die Tumorbiologie und sind Ausgangspunkt zur Translation der funktionellen Signalwegskartierung in die molekulare in-vitro-Diagnostik., In oncology a clear trend away from systemic therapies towards targeted treatment was recognizable in recent years. For some tumor types, like for example breast cancer, several molecular markers are available to support both treatment decision and personalised therapy. However problems still occur when it comes to the quantitative determination of these markers in clinical relevant, formalin-fixed tissues. Moreover in many entities only very little is known about the tumor biology. This knowledge however would be necessary to systematically identify novel molecular marker. The extraction of proteins from clinical tissues which was developed during the last years is an important step to overcome the mentioned obstacles. However, the current protocols are stretched to their limits if long-time stored or over-fixed samples are used for protein extraction. To deal with this issue an enhanced extraction protocol was developed in this thesis. Applying the optimised method the determination of three molecular breast cancer markers (uPA, PAI-1, HER2) should be enabled. For the two invasion-associated proteins uPA and PAI-1 this should be achieved first by using the clinically approved Femtelle-ELISA. Yet, this assay turned out to be incompatible with denatured proteins from formalin-fixed tissues. Not until the application of the Reverse Phase Protein Microarry (RPPA) approach it was possible to determine uPA and PAI-1 together with their associated protein networks. This high-throughput technology allows the parallel screening of a plurality of tumors for the expression and activation of whole protein networks. This method was also used for an absolute HER2 quantification from fixed tissue which was reached for the first time in this study. Furthermore capitalising the mentioned advantages of the RPPA, p-HER2 could be identified as a potential biomarker in breast cancer patients and p-HSP27(Ser15) and HER2 as markers in oesophageal adenocarcinoma. In conclusion, the resul

Bei neuen Ansätzen zur Behandlung von Tumorpatienten nimmt die umfassende Charakterisierung deregulierter Signalproteine im erkrankten Gewebe eine Schlüsselrolle ein. Damit lassen sich zum einen Zielstrukturen für effektivere Therapien entwickeln, zum anderen stellen abnormal aktivierte Signalmoleküle Biomarker dar, um Patienten für diese neuen Therapieoptionen auswählen zu können. In meiner Arbeit habe ich zunächst die Proteinextraktion aus klinischen Tumorproben (Formalin-fixierte Brustkrebsgewebe) optimiert. Durch den nachfolgenden Einsatz der Hochdurchsatztechnik des „Reverse Phase Protein Arrays“ konnten in den Tumorzelllysaten erstmals Therapie-relevante Markerproteine (u.a. HER2, uPA und PAI-1) und deren assoziierte Netzwerke quantitativ dargestellt werden. Die Ergebnisse dieser Arbeit liefern ein besseres Verständnis für die Tumorbiologie und sind Ausgangspunkt zur Translation der funktionellen Signalwegskartierung in die molekulare in-vitro-Diagnostik., In oncology a clear trend away from systemic therapies towards targeted treatment was recognizable in recent years. For some tumor types, like for example breast cancer, several molecular markers are available to support both treatment decision and personalised therapy. However problems still occur when it comes to the quantitative determination of these markers in clinical relevant, formalin-fixed tissues. Moreover in many entities only very little is known about the tumor biology. This knowledge however would be necessary to systematically identify novel molecular marker. The extraction of proteins from clinical tissues which was developed during the last years is an important step to overcome the mentioned obstacles. However, the current protocols are stretched to their limits if long-time stored or over-fixed samples are used for protein extraction. To deal with this issue an enhanced extraction protocol was developed in this thesis. Applying the optimised method the determination of three molecular breast cancer markers (uPA, PAI-1, HER2) should be enabled. For the two invasion-associated proteins uPA and PAI-1 this should be achieved first by using the clinically approved Femtelle-ELISA. Yet, this assay turned out to be incompatible with denatured proteins from formalin-fixed tissues. Not until the application of the Reverse Phase Protein Microarry (RPPA) approach it was possible to determine uPA and PAI-1 together with their associated protein networks. This high-throughput technology allows the parallel screening of a plurality of tumors for the expression and activation of whole protein networks. This method was also used for an absolute HER2 quantification from fixed tissue which was reached for the first time in this study. Furthermore capitalising the mentioned advantages of the RPPA, p-HER2 could be identified as a potential biomarker in breast cancer patients and p-HSP27(Ser15) and HER2 as markers in oesophageal adenocarcinoma. In conclusion, the resul

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

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

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

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.

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

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

Background and purpose: Cost-of-illness studies often describe a single aggregate cost of a disease state. This approach is less helpful for a condition with a spectrum of outcomes like stroke. The modified Rankin Scale is the most commonly used outcome measure for stroke. We sought to describe the existing evidence on the costs of stroke according to individual modified Rankin Scale categories. This may be useful in future cost effectiveness modelling studies of interventions where cost data have not been collected, but disability outcome is known. Methods: Systematic review of the published literature, searching electronic databases between 2004 and 2015 using validated search filters. Results were screened to identify studies presenting costs by individual modified Rankin Scale categories. Results: Of 17,782 unique identified articles, 13 matched all inclusion criteria. In only four of these studies were costs reported by modified Rankin Scale categories. Most studies included direct medical costs only. Societal costs were assessed in two studies. Overall, studies had a high methodological and reporting quality. The heterogeneity in costing methods used in the identified studies prevented meaningful comparison of the reported cost data. Despite this limitation, the costs consistently increased with greater severity (increasing modified Rankin Scale score). Conclusions: Few cost studies of stroke include information based on stroke recovery measured by individual modified Rankin Scale categories and the existing data are limited. To reliably capture this information, future studies are needed that preferably apply standardised costing methods to promote greater potential for use in cost-effectiveness analyses whereby direct collection of patient-level resource use has not been possible.

The response of coastal wetlands to sea level rise (SLR) during the 21st century remains uncertain. Global-scale projections suggest that between 20% and 90% (for low and high SLR scenarios, respectively) of the present-day coastal wetland area will be lost, including the loss of biodiversity and highly valued ecosystem services. These projections do not necessarily take into account all essential geomorphological and socio-economic system feedbacks. Here we present an integrated global modelling approach that considers (i) the ability of coastal wetlands to build up vertically by sediment accretion and (ii) the accommodation space, namely the vertical and lateral space available for fine sediments to accumulate and to be colonised by wetland vegetation. We use this approach to assess global-scale changes in coastal wetland area in response to global SLR and anthropogenic coastal occupation during the 21st century. Based on our simulations we find that, globally, wetland gains of up to 60% of the current area are expected, if more than 37% of coastal wetlands have sufficient accommodation space, and sediment supply remains at present levels. In contrast to previous studies, we project that until 2100 global coastal wetland loss will range between 0% and 30%, assuming no additional accommodation space. Our simulations suggest that global wetland resilience is primarily driven by the availability of accommodation space, which is strongly influenced by the building of anthropogenic infrastructure in the coastal zone and its expected to change over the 21st century. Rather than being an inevitable consequence of global SLR, our findings indicate that large-scale coastal wetland loss might be avoidable, if sufficient additional accommodation space can be created through innovative “nature-based adaptation” solutions to coastal management.

This study explores the uncertainty introduced in global assessments of coastal flood exposure and risk when not accounting for water-level attenuation due to land-surface characteristics. We implement a range of plausible water-level attenuation values for characteristic land-cover classes in the flood module of the Dynamic and Integrated Vulnerability Assessment (DIVA) modelling framework and assess the sensitivity of flood exposure and flood risk indicators to differences in attenuation rates. Results show a reduction of up to 44 % in area exposure and even larger reductions in population exposure and expected flood damages when considering water-level attenuation. The reductions vary by country, reflecting the differences in the physical characteristics of the floodplain as well as in the spatial distribution of people and assets in coastal regions. We find that uncertainties related to not accounting for water attenuation in global assessments of flood risk are of similar magnitude to the uncertainties related to the amount of sea-level rise expected over the 21st century. Despite using simplified assumptions to account for the process of water-level attenuation, which depends on numerous factors and their complex interactions, our results strongly suggest that an improved understanding and representation of the temporal and spatial variation of water levels across floodplains is essential for future impact modelling.

Background and purpose: Cost-of-illness studies often describe a single aggregate cost of a disease state. This approach is less helpful for a condition with a spectrum of outcomes like stroke. The modified Rankin Scale is the most commonly used outcome measure for stroke. We sought to describe the existing evidence on the costs of stroke according to individual modified Rankin Scale categories. This may be useful in future cost effectiveness modelling studies of interventions where cost data have not been collected, but disability outcome is known. Methods: Systematic review of the published literature, searching electronic databases between 2004 and 2015 using validated search filters. Results were screened to identify studies presenting costs by individual modified Rankin Scale categories. Results: Of 17,782 unique identified articles, 13 matched all inclusion criteria. In only four of these studies were costs reported by modified Rankin Scale categories. Most studies included direct medical costs only. Societal costs were assessed in two studies. Overall, studies had a high methodological and reporting quality. The heterogeneity in costing methods used in the identified studies prevented meaningful comparison of the reported cost data. Despite this limitation, the costs consistently increased with greater severity (increasing modified Rankin Scale score). Conclusions: Few cost studies of stroke include information based on stroke recovery measured by individual modified Rankin Scale categories and the existing data are limited. To reliably capture this information, future studies are needed that preferably apply standardised costing methods to promote greater potential for use in cost-effectiveness analyses whereby direct collection of patient-level resource use has not been possible.

Background and purpose: Cost-of-illness studies often describe a single aggregate cost of a disease state. This approach is less helpful for a condition with a spectrum of outcomes like stroke. The modified Rankin Scale is the most commonly used outcome measure for stroke. We sought to describe the existing evidence on the costs of stroke according to individual modified Rankin Scale categories. This may be useful in future cost effectiveness modelling studies of interventions where cost data have not been collected, but disability outcome is known. Methods: Systematic review of the published literature, searching electronic databases between 2004 and 2015 using validated search filters. Results were screened to identify studies presenting costs by individual modified Rankin Scale categories. Results: Of 17,782 unique identified articles, 13 matched all inclusion criteria. In only four of these studies were costs reported by modified Rankin Scale categories. Most studies included direct medical costs only. Societal costs were assessed in two studies. Overall, studies had a high methodological and reporting quality. The heterogeneity in costing methods used in the identified studies prevented meaningful comparison of the reported cost data. Despite this limitation, the costs consistently increased with greater severity (increasing modified Rankin Scale score). Conclusions: Few cost studies of stroke include information based on stroke recovery measured by individual modified Rankin Scale categories and the existing data are limited. To reliably capture this information, future studies are needed that preferably apply standardised costing methods to promote greater potential for use in cost-effectiveness analyses whereby direct collection of patient-level resource use has not been possible.

Background and purpose: Cost-of-illness studies often describe a single aggregate cost of a disease state. This approach is less helpful for a condition with a spectrum of outcomes like stroke. The modified Rankin Scale is the most commonly used outcome measure for stroke. We sought to describe the existing evidence on the costs of stroke according to individual modified Rankin Scale categories. This may be useful in future cost effectiveness modelling studies of interventions where cost data have not been collected, but disability outcome is known. Methods: Systematic review of the published literature, searching electronic databases between 2004 and 2015 using validated search filters. Results were screened to identify studies presenting costs by individual modified Rankin Scale categories. Results: Of 17,782 unique identified articles, 13 matched all inclusion criteria. In only four of these studies were costs reported by modified Rankin Scale categories. Most studies included direct medical costs only. Societal costs were assessed in two studies. Overall, studies had a high methodological and reporting quality. The heterogeneity in costing methods used in the identified studies prevented meaningful comparison of the reported cost data. Despite this limitation, the costs consistently increased with greater severity (increasing modified Rankin Scale score). Conclusions: Few cost studies of stroke include information based on stroke recovery measured by individual modified Rankin Scale categories and the existing data are limited. To reliably capture this information, future studies are needed that preferably apply standardised costing methods to promote greater potential for use in cost-effectiveness analyses whereby direct collection of patient-level resource use has not been possible.