Holistic valuation of Nature-Based Solutions accounting for human perceptions and nature benefits.

When assessing strategies for implementing Nature-Based Solutions (NBS), it is paramount to identify and quantify all benefits for securing better, informed decisionmaking. Nevertheless, there appears to be a lack of primary data for linking the valuation of NBS sites with the preferences and attitudes of people interacting with them and their connection to supporting efforts to reduce biodiversity loss. This is a critical gap, as the socio-cultural context of NBS has been proven to play a big role in NBS valuation, especially for their non-tangible benefits (e.g. physical and psychological well-being, habitat enhancements, etc.). Consequently, through cocreation with the local government, we co-designed a contingent valuation (CV) survey to explore how the valuation of NBS sites may be shaped by their relationship with the users and the specific respondent and site characteristics. We applied this method to a case study of two distinct areas located in Aarhus, Denmark, with notable differences related to their attributes (e.g. size, location, time passed since construction). The esults obtained from 607 households in Aarhus Municipality show that the personal preferences of the respondent are the most relevant driver of value, surpassing both the perceptions linked to the physical features of the NBS and the socio-economic characteristics of the respondents. Specifically, the respondents attributing most importance to nature benefits were the ones assigning a higher value to the NBS and being willing to pay more for an improvement of the nature quality in the area. These findings highlight the relevance of applying a method assessing the interconnections between human perceptions and nature benefits to ensure a holistic valuation and purposeful design of NBS.

UAV Image-Based Crop Growth Analysis of 3D-Reconstructed Crop Canopies.

Plant growth rate is an essential phenotypic parameter for quantifying potential crop productivity. Under field conditions, manual measurement of plant growth rate is less accurate in most cases. Image-based high-throughput platforms offer great potential for rapid, non-destructive, and objective estimation of plant growth parameters. The aim of this study was to assess the potential for quantifying plant growth rate using UAV-based (unoccupied aerial vehicle) imagery collected multiple times throughout the growing season. In this study, six diverse lines of lentils were grown in three replicates of 1 m2 microplots with six biomass collection time-points throughout the growing season over five site-years. Aerial imagery was collected simultaneously with each manual measurement of the above-ground biomass time-point and was used to produce two-dimensional orthomosaics and three-dimensional point clouds. Non-linear logistic models were fit to multiple data collection points throughout the growing season. Overall, remotely detected vegetation area and crop volume were found to produce trends comparable to the accumulation of dry weight biomass throughout the growing season. The growth rate and G50 (days to 50% of maximum growth) parameters of the model effectively quantified lentil growth rate indicating significant potential for image-based tools to be used in plant breeding programs. Comparing image-based groundcover and vegetation volume estimates with manually measured above-ground biomass suggested strong correlations. Vegetation area measured from a UAV has utility in quantifying lentil biomass and is indicative of leaf area early in the growing season. For mid- to late-season biomass estimation, plot volume was determined to be a better estimator. Apart from traditional traits, the estimation and analysis of plant parameters not typically collected in traditional breeding programs are possible with image-based methods, and this can create new opportunities to improve breeding efficiency mainly by offering new phenotypes and affecting selection intensity.

Assessing the recreational value of small-scale nature-based solutions when planning urban flood adaptation.

Nature-based solutions may actively reduce hydro-meteorological risks in urban areas as a part of climate change adaptation. However, the main reason for the increasing uptake of this type of solution is their many benefits for the local inhabitants, including recreational value. Previous studies on recreational value focus on studies of existing nature sites that are often much larger than what is considered as new NBS for flood adaptation studies in urban areas. We thus prioritized studies with smaller areas and nature types suitable for urban flood adaptation and divided them into four common nature types for urban flood adaptation: sustainable urban drainage systems, city parks, nature areas and rivers. We identified 23 primary valuation studies, including both stated and revealed preference studies, and derived two value transfer functions based on meta-regression analysis on existing areas. We investigated trends between values and variables and found that for the purpose of planning of new NBS the size of NBS and population density were determining factors of recreational value. For existing NBS the maximum travelling distance may be included as well. We find that existing state-of-the-art studies overestimate the recreational with more than a factor of 4 for NBS sizes below 5 ha. Our results are valid in a European context for nature-based solutions below 250 ha and can be applied across different NBS types and sizes.

Knowledge gaps and future research needs for assessing the non-market benefits of Nature-Based Solutions and Nature-Based Solution-like strategies.

Nature-Based Solutions (NBS) can be defined as solutions based on natural processes that meet societal challenges and simultaneously provide human well-being and biodiversity benefits. These solutions are envisioned to contribute to operationalizing sustainable development strategies, especially in the context of adaptation to climate change (e.g. flood risk reduction). In order to quantify NBS performance, ease their uptake and advocate for them as alternatives to "business-as-usual" infrastructures, a comprehensive, holistic valuation of their multiple benefits (multiple advantages and disadvantages) is needed. This entails quantifying non-market benefits for people and nature in addition to determining the (direct) cost-benefit of the risk-reduction measure. Despite the importance given to the assessment of non-tangible benefits for people and nature in the literature, systematic data collection on these dimensions seems to be missing. This study reviews publications that used stated preference methods to assess non-market human benefits of NBS and NBS-like strategies. Its aim is to highlight any biases or knowledge gaps in this kind of evaluation. Our results show that the valuation of non-tangible benefits of NBS (e.g. increased recreation and well-being, enhanced biodiversity) still suffers from a lack of common framing. Despite some steps being taken on enabling interconnected benefit assessments, unexploited opportunities concerning the integrated assessment of non-market human and nature benefits predominate. Moreover, the research to-date appears based on a case-to-case approach, and thus a shared holistic method does not emerge from the present literature, potentially delaying the uptake of NBS. We argue that future research could minimize missed opportunities by focusing on and systematically applying holistic benefits assessments. Methods based on stated preference surveys may help to ensure holistic approaches are taken, as well as contributing to their replicability and application when upscaling NBS.

Peritoneal metastases found in routinely resected specimens after cytoreductive surgery and heated intraperitoneal chemotherapy.

INTRODUCTION: Peritoneal metastases (PM) originating from colorectal cancer (CRC) and pseudomyxoma peritonei (PMP) can be treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Certain sites in the peritoneal cavity are prone to contain PM and are, therefore, routinely resected. The aim of this study is to investigate the frequency of disease in CRS specimens routinely resected. Secondly, to investigate if the risk of finding PM in routinely resected specimen is associated with involvement of anatomic related peritoneal areas. MATERIALS AND METHODS: This study investigated 433 patients diagnosed with PMP (n = 119) or PM from CRC (n = 314) and operated with CRS + HIPEC between June 2006 and November 2020 at a national center. Baseline data were prospectively registered. Pathology reports were reviewed for the presence of metastases in the routinely resected umbilicus, ligamentum teres hepatis, ovaries and greater omentum. Tumor extent was estimated using the Dutch region count. RESULTS: PM was found in 14.7% of umbilical resections, in 17.4% of the resected ligamentum teres hepatis, in 48.2% of the resected ovaries and in 49.5% of the greater omentum specimens. We found an association between macroscopic disease involvement of the nearest region and risk of PM found in the related resections. Seven of 31 women with no macroscopically visible disease in the pelvis had PM diagnosed in the resected ovaries. CONCLUSIONS: A substantial proportion of routine resections held histologic verified PM. Our results may advocate for a routinely performed resection of the umbilicus, ligamentum teres hepatis, ovaries and greater omentum.

MET deletion is a frequent event in gastric/gastroesophageal junction/esophageal cancer: a cross-sectional analysis of gene status and signal distribution in 1,580 patients.

BACKGROUND: MET gene aberrations are found in several human cancers including gastric, ovarian and lung. In a large multinational cohort of patients with gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma we assessed the MET status with respect to amplification and deletion and correlate the results with the phenotypical gene signal distribution pattern. METHODS: Tissue specimens from 1,580 patients were analyzed using a novel fluorescence in situ hybridization (FISH) assay employing a MET/CEN-7 IQFISH Probe Mix. MET amplification and deletions were defined as a MET/CEN-7 ratio ≥2.0 and a MET/CEN-7 ratio <0.8, respectively. Furthermore, the link between the MET gene status and the phenotypical signal distribution was investigated. RESULTS: The prevalence of MET amplification and deletions was found to be 7.2% and 8.7%, respectively. Significant differences were observed with regard to geographic regions and sex. The Asian population had the highest percentage of MET amplification (9.4%) and the lowest percentage of deletions (3.2%). MET deletions was found more frequently among males (10.1%) compared to females (5.3%) and in esophagus (17.6%) compared to the stomach (5.7%). More than 50% of the patients who harbored MET gene amplification had a heterogeneous distribution of the FISH signals. Patients with a focal signal distribution were solely to be found among the MET amplified population. MET deletion were mainly observed in the group of patients with a homogenous signal distribution. CONCLUSIONS: The screening data from this cross-sectional study showed that MET deletion and amplification are frequent events in G/GEJ/E cancer, which are linked to different phenotypical signal distribution patterns. The role of MET deletion in relation to tumor development is not fully understood but it is likely to play a role in the oncogenic transformation of the cells.

FOETAL for NCD-FOetal Exposure and Epidemiological Transitions: the role of Anaemia in early Life for Non-Communicable Diseases in later life: a prospective preconception study in rural Tanzania.

PURPOSE: Low-income and middle-income countries such as Tanzania experience a high prevalence of non-communicable diseases (NCDs), including anaemia. Studying if and how anaemia affects growth, placenta development, epigenetic patterns and newborns' risk of NCDs may provide approaches to prevent NCDs. PARTICIPANTS: The FOETALforNCD (FOetal Exposure and Epidemiological Transitions: the role of Anaemia in early Life for Non-Communicable Diseases in later life) Study is a population-based preconception, pregnancy and birth cohort study (n=1415, n=538, n=427, respectively), conducted in a rural region of North-East Tanzania. All participants were recruited prior to conception or early in pregnancy and followed throughout pregnancy as well as at birth. Data collection included: maternal blood, screening for NCDs and malaria, ultrasound in each trimester, neonatal anthropometry at birth and at 1 month of age, cord blood, placental and cord biopsies for stereology and epigenetic analyses. FINDINGS TO DATE: At preconception, the average age, body mass index and blood pressure of the women were 28 years, 23 kg/m2 and 117/75 mm Hg, respectively. In total, 458 (36.7%) women had anaemia (haemoglobin Hb <12 g/dL) and 34 (3.6%) women were HIV-positive at preconception. During pregnancy 359 (66.7%) women had anaemia of which 85 (15.8%) women had moderate-to-severe anaemia (Hb ≤9 g/dL) and 33 (6.1%) women had severe anaemia (Hb ≤8 g/dL). In total, 185 (34.4%) women were diagnosed with malaria during pregnancy. FUTURE PLANS: The project will provide new knowledge on how health, even before conception, might modify the risk of developing NCDs and how to promote better health during pregnancy. The present project ended data collection 1 month after giving birth, but follow-up is continuing through regular monitoring of growth and development and health events according to the National Road Map Strategic Plan in Tanzania. This data will link fetal adverse event to childhood development, and depending on further grant allocation, through a life course follow-up.

Anemia in late pregnancy induces an adaptive response in fetoplacental vascularization.

INTRODUCTION: Anemia during pregnancy may compromise fetal and newborn's health, however, little is known about how and when the fetoplacental vascularization is most vulnerable to anemia. METHODS: Using systematic and isotropic uniform random sampling, placental samples were collected from 189 placentas in a cohort study of Tanzanian women whose hemoglobin concentration was measured throughout pregnancy. Fetoplacental vessels and villi were defined as exerting either a transport or diffusion function. The vascularization patterns for transport and diffusion vessels and villi were assessed by stereology. Blood vessel length, surface area and diffusion distance as well as placental villi volume were calculated. RESULTS: Anemia from a gestational age of 23 weeks was significantly associated with increased fetoplacental vascularization in vessels and villi compared to women who were non-anemic throughout pregnancy. Transport surface vessel area: 0.31 m2 [95% CI: 0.18-0.55], P = 0.01; Transport villi volume 19.8 cm3 [95% CI: 6.37-33.2], P = 0.004, Transport vessel diameter 7.23 µm [95% CI: 1.23-13.3], P = 0.02. Diffusion vessel surface: 3.23 m2 [95% CI: 1.55-4.91], P < 0.001 and diffusion villi volume: 29.8 cm3 [95% CI: 10.0-49.5], P = 0.003). Finally, all the measured transport vessel and villi significantly parameters and diffusion vessel surface, vessel diameter and diffusion distance were associated with birth weight. DISCUSSION: Increased fetoplacental vascularization related to anemia from a gestational age of 23 weeks in pregnancy together with the association between fetoplacental vascularity and birth weight suggest that the timing of anemia determines the effect on fetoplacental vascularization and underlines the clinical relevance for proper development of fetoplacental vasculature.

Life cycle assessment of point source emissions and infrastructure impacts of four types of urban stormwater systems.

The implementation, operation and decommissioning of stormwater management systems causes environmental damage, while at the same time reducing pollutant loads in receiving waters by treating stormwater. The focus in research has been either on assessing impacts caused by stormwater infrastructure, or risks associated with stormwater discharges, but rarely have these two sources of environmental impacts been combined to allow a comprehensive environmental evaluation of stormwater management. We assess the environmental sustainability of four different generic stormwater management systems for a catchment of 260ha by a) modelling the flow of pollutants in stormwater, and resulting point source emissions to freshwater, and b) quantifying emissions and resources for all relevant processes associated with the life cycle of the infrastructure. Using life cycle impact assessment, we quantify the resulting environmental impacts and consequent damage to two areas of protection - ecosystems (expressed in time-integrated species loss) and natural resource availability (expressed in extra costs for future resource extraction). Our assessment shows that combined stormwater management causes the highest damage to both ecosystems (1.4E-03 species.yr/yr) and resource availability (8.8E+03 USD/yr). Separate systems using only green infrastructure were found to avoid damage to resource availability (-3.7 to -5.2 USD/yr) and cause lower ecosystem damage (1.1-1.3E-03 species.yr/yr). Stormwater discharges contribute significantly to the total ecosystem damage of the different systems (36-88%), and the sustainability of separate systems can be further improved by optimizing the removal efficiency of low-tech elements like surface basins and filter soil. The systems are designed according to engineering standards. Choosing different criteria, e.g. identical flood safety levels, would result in substantial changes of the relative performance of the systems. The findings highlight the importance of including point source emissions into the assessment to allow comparative conclusions and minimisation of environmental damage of stormwater management.

Pollution levels of stormwater discharges and resulting environmental impacts.

Stormwater carries pollutants that potentially cause negative environmental impacts to receiving water bodies, which can be quantified using life cycle impact assessment (LCIA). We compiled a list of 20 metals, almost 300 organic compounds, and nutrients potentially present in stormwater, and measured concentrations reported in literature. We calculated mean pollutant concentrations, which we then translated to generic impacts per litre of stormwater discharged, using existing LCIA characterisation factors. Freshwater and marine ecotoxicity impacts were found to be within the same order of magnitude (0.72, and 0.82 CTUe/l respectively), while eutrophication impacts were 3.2E-07 kgP-eq/l for freshwater and 2.0E-06 kgN-eq/l for marine waters. Stormwater discharges potentially have a strong contribution to ecotoxicity impacts compared to other human activities, such as human water consumption and agriculture. Conversely, contribution to aquatic eutrophication impacts was modest. Metals were identified as the main contributor to ecotoxicity impacts, causing >97% of the total impacts. This is in line with conclusions from a legal screening, where metals showed to be problematic when comparing measured concentrations against existing environmental quality standards.

Malaria in Early Pregnancy and the Development of the Placental Vasculature.

BACKGROUND: Pregnancy malaria has a negative impact on fetal outcome. It is uncertain whether infections in early pregnancy have a clinical impact by impeding the development of the placental vasculature. METHODS: Tanzanian women (n = 138) were closely monitored during pregnancy. Placentas collected at birth were investigated using stereology to establish the characteristics of placental villi and vessels. Placental vasculature measures were compared between women infected with malaria and controls. RESULTS: Compared with controls, placentas from women infected with malaria before a gestational age (GA) of 15 weeks had a decreased volume of transport villi (mean decrease [standard deviation], 12.45 [5.39] cm3; P = .02), an increased diffusion distance in diffusion vessels (mean increase, 3.33 [1.27] µm; P = .01), and a compensatory increase in diffusion vessel surface area (mean increase, 1.81 [0.74 m2]; P = .02). In women who had malaria before a GA of 15 weeks diffusion vessel surface area and transport vessel length distance were positive predictors for birth weight (multilinear regression: P = .007 and P = .055 for diffusion surface area and transport length, respectively) and GA at delivery (P = .005 and P = .04). CONCLUSIONS: Malaria infection in early pregnancy impedes placental vascular development. The resulting phenotypic changes, which can be detected at delivery, are associated with birth weight and gestational length. CLINICAL TRIALS REGISTRATION: NCT02191683.

Evaluating catchment response to artificial rainfall from four weather generators for present and future climate.

The technical lifetime of urban water infrastructure has a duration where climate change has to be considered when alterations to the system are planned. Also, models for urban water management are reaching a very high complexity level with, for example, decentralized stormwater control measures being included. These systems have to be evaluated under as close-to-real conditions as possible. Long term statistics (LTS) modelling with observational data is the most close-to-real solution for present climate conditions, but for future climate conditions artificial rainfall time series from weather generators (WGs) have to be used. In this study, we ran LTS simulations with four different WG products for both present and future conditions on two different catchments. For the present conditions, all WG products result in realistic catchment responses when it comes to the number of full flowing pipes and the number and volume of combined sewer overflows (CSOs). For future conditions, the differences in the WGs representation of the expectations to climate change is evident. Nonetheless, all future results indicate that the catchments will have to handle more events that utilize the full capacity of the drainage systems. Generally, WG products are relevant to use in planning of future changes to sewer systems.

A framework for performing comparative LCA between repairing flooded houses and construction of dikes in non-stationary climate with changing risk of flooding.

Sustainable flood management is a basic societal need. In this article, life cycle assessment is used to compare two ways to maintain the state of a coastal urban area in a changing climate with increasing flood risk. On one side, the construction of a dike, a hard and proactive scenario, is modelled using a bottom up approach. On the other, the systematic repair of houses flooded by sea surges, a post-disaster measure, is assessed using a Monte Carlo simulation allowing for aleatory uncertainties in predicting future sea level rise and occurrences of extreme events. Two metrics are identified, normalized mean impacts and probability of dike being most efficient. The methodology is applied to three case studies in Denmark representing three contrasting areas, Copenhagen, Frederiksværk, and Esbjerg. For all case studies the distribution of the calculated impact of repairing houses is highly right skewed, which in some cases has implications for the comparative LCA. The results show that, in Copenhagen, the scenario of the dike is overwhelmingly favorable for the environment, with a 43 times higher impact for repairing houses and only 0% probability of the repairs being favorable. For Frederiksværk and Esbjerg the corresponding numbers are 5 and 0.9 times and 85% and 32%, respectively. Hence constructing a dike at this point in time is highly recommended in Copenhagen, preferable in Frederiksværk, and probably not recommendable in Esbjerg.

Initial conditions of urban permeable surfaces in rainfall-runoff models using Horton's infiltration.

Infiltration is a key process controlling runoff, but varies depending on antecedent conditions. This study provides estimates on initial conditions for urban permeable surfaces via continuous simulation of the infiltration capacity using historical rain data. An analysis of historical rainfall records show that accumulated rainfall prior to large rain events does not depend on the return period of the event. Using an infiltration-runoff model we found that for a typical large rain storm, antecedent conditions in general lead to reduced infiltration capacity both for sandy and clayey soils and that there is substantial runoff for return periods above 1-10 years.

Cervical screening in Denmark - a success followed by stagnation.

INTRODUCTION: Despite an intensive screening activity, the incidence of cervical cancer in Denmark has remained stable for the last 15 years, while regional differences have increased. To search for explanations, we investigated possible weaknesses in the screening program. MATERIAL AND METHODS: Data on the screen-targeted women were retrieved from Statistics Denmark. Data on screening activity were retrieved from the annual reports from 2009 to 2015 on quality of cervical screening. Coverage was calculated as proportion of screen-targeted women with at least one cytology sample within recommended time intervals. Insufficient follow-up was calculated as proportion of abnormal and unsatisfactory samples not followed up within recommended time intervals. Diagnostic distribution was calculated for samples with a satisfactory cytology diagnosis. RESULTS: Coverage remained stable at 75%-76% during the study period. Annually, approximately 100,000 women are screened before they are eligible for invitation, and 600,000 invitations and reminders are issued resulting in screening of 200,000 women. In 2009, 21% of abnormal and unsatisfactory samples were not followed up within the recommended time interval; a proportion that had decreased to 15% in 2015. Overall, 11% of satisfactory samples with a cytology diagnosis were abnormal, but with surprising variation from 6% to 15% across regions. DISCUSSION: The success of a screening program depends first of all on coverage and timely follow-up of abnormal findings. Our analysis indicated that the currently high incidence of cervical cancer in Denmark may partly be due to low screening coverage. Also worrisome is a high proportion of non-timely follow-up of abnormal findings. Innovative ways to improve coverage and follow-up are urgently needed.

Methemoglobin reductase activity in intact fish red blood cells.

Red blood cells (RBCs) possess methemoglobin reductase activity that counters the ongoing oxidation of hemoglobin (Hb) to methemoglobin (metHb), which in circulating blood is caused by Hb autoxidation or reactions with nitrite. We describe an assay for determining metHb reductase activity in intact RBCs in physiological saline at normal Pco2 and pH. After initial loading of oxygenated RBCs with nitrite (partly oxidizing Hb to metHb), the nitrite is removed by three washes of the RBCs in nitrite-free physiological saline to enable the detection of RBC metHb reductase activity in the absence of counteracting oxidation. This assay was used to compare metHb reduction in rainbow trout and carp RBCs under both oxygenated and deoxygenated conditions. Washing resulted in effective wash-out of nitrite to low and safe values (~2µM). The subsequent decline in [metHb] with time followed first-order kinetics, allowing characterization of metHb reductase activity through the first order rate constant k. In oxygenated RBCs at 25°C, the k values for rainbow trout and carp were slightly below or above 0.01min-1, respectively; which is double the value reported for mammals at 37°C. We conclude the higher metHb reductase activity in fish offsets their higher Hb autoxidation and higher likelihood of encountering elevated nitrite. Deoxygenation significantly raised the rates of RBC metHb reduction, and more so in rainbow trout than in carp. The temperature sensitivity of metHb reduction in rainbow trout RBCs was high (Q10 ~2.8) and instrumental in handling increased Hb autoxidation with temperature.

Detection of MET amplification in gastroesophageal tumor specimens using IQFISH.

BACKGROUND: The gene mesenchymal epithelial transition factor (MET) is a proto-oncogene that encodes a transmembrane receptor with intrinsic tyrosine kinase activity known as Met or cMet. MET is found to be amplified in several human cancers including gastroesophageal cancer. METHODS: Here we report the MET amplification prevalence data from 159 consecutive tumor specimens from patients with gastric (G), gastroesophageal junction (GEJ) and esophageal (E) adenocarcinoma, using a novel fluorescence in situ hybridization (FISH) assay, MET/CEN-7 IQFISH Probe Mix [an investigational use only (IUO) assay]. MET amplification was defined as a MET/CEN-7 ratio ≥2.0. Furthermore, the link between the MET signal distribution and amplification status was investigated. RESULTS: The prevalence of MET amplification was found to be 6.9%. The FISH assay demonstrated a high inter-observer reproducibility. The inter-observer results showed a 100% overall agreement with respect to the MET status (amplified/non-amplified). The inter-observer CV was estimated to 11.8% (95% CI: 10.2-13.4). For the signal distribution, the inter-observer agreement was reported to be 98.7%. We also report an association of MET amplification and a unique signal distribution pattern in the G/GEJ/E tumor specimens. We found that the prevalence of MET amplification was markedly higher in tumors specimens with a heterogeneous (66.7%) versus homogeneous (2.0%) signal distribution. Furthermore, specimens with a heterogeneous signal distribution had a statically significantly higher median MET/CEN-7 ratio (2.35 versus 1.04; P<0.0001). CONCLUSIONS: The novel FISH assay showed a high inter-observer reproducibility both with respect to amplification status and signal distribution. Based on the finding in the study it is suggested that MET amplification mainly is associated with tumor cells that is represented by a heterogonous growth pattern.

Gene Signal Distribution and HER2 Amplification in Gastroesophageal Cancer.

Background: HER2 serves as an important therapeutic target in gastroesophageal cancer. Differences in HER2 gene signal distribution patterns can be observed at the tissue level, but how it influences the HER2 amplification status has not been studied so far. Here, we investigated the link between HER2 amplification and the different types of gene signal distribution. Methods: Tumor samples from 140 patients with gastroesophageal adenocarcinoma where analyzed using the HER2 IQFISH pharmDx™ assay. Specimens covered non-amplified and amplified cases with a preselected high proportion of HER2 amplified cases. Based on the HER2/CEN-17 ratio, specimens were categorized into amplified or non-amplified. The signal distribution patterns were divided into homogeneous, heterogeneous focal or heterogeneous mosaic. The study was conducted based on anonymized specimens with limited access to clinicopathological data. Results: Among the 140 analyzed specimens 83 had a heterogeneous HER2 signal distribution, with 62 being focal and 21 of the mosaic type. The remaining 57 specimens had a homogeneous signal distribution. HER2 amplification was observed in 63 of the 140 specimens, and nearly all (93.7%) were found among specimens with a heterogeneous focal signal distribution (p<0.0001). The mean HER2/CEN-17 ratio for the focal heterogeneous group was 8.75 (CI95%: 6.87 - 10.63), compared to 1.53 (CI95%: 1.45 - 1.61) and 1.70 (CI95%: 1.22 - 2.18) for the heterogeneous mosaic and homogeneous groups, respectively, (p<0.0001). Conclusions: A clear relationship between HER2 amplification and the focal heterogeneous signal distribution was demonstrated in tumor specimens from patients with gastroesophageal cancer. Furthermore, we raise the hypothesis that the signal distribution patterns observed with FISH might be related to different subpopulations of HER2 positive tumor cells.

Melanomas of the vulva and vagina.

INTRODUCTION: Malignant melanoma is a rare type of cancer in the vagina and vulva associated with a poor prognosis due to late diagnosis and early dissemination. Only a limited amount of literature exists on the condition. This study elucidates the effect of current treatment. METHODS: All patients diagnosed with malignant melanoma in the vagina or vulva at Aarhus University Hospital, Skejby, Denmark, in the period from 1996 to 2013 were included. Data were collected from the electronic patient records and from the Danish Pathology Register. RESULTS: A total of 17 patients were included. The average age at the time of diagnosis was 77 years and the median overall survival time was 21.9 months. The five-year survival in this study was 17.7%. The majority of the melanomas were nodular and all of the superficially spreading melanomas were found in the vulva only. Malignant melanoma in the vagina has a poorer prognosis than in the vulva as it is diagnosed later. CONCLUSIONS: Early diagnosis and staging of this cancer is important. Positron emission tomography-computed tom-ography should be the standard method for staging the disease. Older women with vaginal discharge should always have a gynaecological examination. The primary treatment is resection of the tumour, but future treatment might be a combination of resection and immunotherapy. FUNDING: none. TRIAL REGISTRATION: not relevant. .