Non-market valuation of the coastal environment - uniting political aims, ecological and economic knowledge

The EU Water Framework Directive (WFD) requires coastal water quality to be classified according to ecological indicators. In this paper, contingent valuation is used to estimate the value of improving the water quality status according to this classification, investigating if this type of holistic political-ecological measure can be related to and valued in monetary terms by the general public. A web-based survey was conducted in two study areas on the Swedish East and West coast. The paper focuses on eutrophication effects, such as bad water clarity, a decrease of bladder wrack stands and algae mats. These water quality elements affect recreational use of coastal areas. Relating to recreational use, two other environmental attributes are addressed – algae blooms and protection of marine areas in terms of e.g. restrictions for boat traffic. The restrictions scenario is also holistic in terms of several imposed restrictions, as well as tightly linked with existing policy. Conducting valuation studies based on a policy-determined measure is beneficial for decisionmakers but also for research e.g. in terms of data availability. It is concluded that these politically defined measures seem to work well as a basis for economic valuation. The respondents are in general both able to understand and to put a monetary value to the measures. This is an important first step, paving the ground for further studies. The monthly mean household WTP between the years 2010 – 2029 ranges from 61 to 108 SEK for improved water quality, from 54 to 84 SEK for less algae blooms and from 32 to 50 SEK for less noise and littering. Regarding noise and littering in archipelago areas in Northern Europe, this is to our knowledge the first WTP estimate that has been presented. The respondents from the East coast region express relatively high mean WTP values compared to the respondents on the West coast for all scenarios. The differences in mean WTP values between the study areas, which are reflected in the transfer errors, indicate that even though the coasts are similar in terms of use and environmental problems, and the respondents have many similar characteristics, a point estimate benefit transfer between the two coasts is not recommended unless high transfer errors are acceptable. WTP is affected by gender, membership of an NGO, whether or not the respondent has children, whether or not the respondent has a foreign background, frequency of visiting the area and whether or not the respondent uses a boat with an engine effect of more than 10 hp while visiting the area.non-market valuation; choice experiments; water framework directive

Benefit Transfer for Environmental Improvements in Coastal Areas: General vs. Specific Models

In this study, we used choice experiment data to analyze the accuracy of benefit transfer (BT) between two case study areas in Sweden for attributes relevant to the implementation of the EU Water Framework Directive and special consideration zones in marine areas. The accuracy and reliability of a BT based on a model including only easily available socioeconomic information is similar to the accuracy of a BT based on a model that gives the best statistical fit, but requires time-consuming data collection. Further, the former model has almost as good a fit as the latter. The BT error varies significantly across the attributes, regardless of which model is used. The results are inconclusive as to whether socioeconomic adjustments improve transfer or not.Choice experiments; Benefits transfer; Water Framework Directive

Shadow detection for improved object tracking in surveillance cameras

Object tracking algorithms and motion triggered alarms are often dis- turbed by shadows. It is challenging to separate between moving objects and shadows since they have similar movement patterns and image prop- erties. In this thesis, three different approaches to detect shadows are developed and evaluated. The identified shadows determine what parts of the image not to track and what alarms to ignore. The first approach utilizes a mathematical model to estimate the intensity attenuation of a shadowed region. The second approach applies thresh- olding to identify shadows based on information about the attenuation, color change and texture preservation. The third approach makes use of probability distributions describing shadows, background and objects. An energy minimization method using discrete optimization is then used in order to classify the pixels as shadow, object or background. All three approaches were evaluated using several different image sequences with corresponding ground truth. Deriving a shadow detection algorithm that is independent of environ- ment and type of objects in the scene turned out to be the major chal- lenge of this thesis. The best result, a true positive rate of 65.5% and a false positive rate of 2.2%, was achieved with the second approach apply- ing intensity, chromaticity and texture. However, there is still a trade-off between the shadow detection and object discrimination. To further im- prove the performance, more features and a more extensive data set could be useful

Cystatin C in the anterior segment of rat and mouse eyes.

Purpose: Cystatin C is a mammalian cysteine protease inhibitor. This study describes the localization of cystatin C in the anterior segment of normal rat and mouse eyes. Cysteine proteases play an important role in protein degradation (e.g. of photoreceptor outer segments in the retinal pigment epithelium) and the balance between these proteases and their specific inhibitors is therefore of great interest. Methods: Cells containing cystatin C were identified by immunohistochemistry and quantified by ELISA. Messenger RNA levels were analysed by quantitative real-time polymerase chain reaction. Results: Cystatin C is present at biologically significant levels in the corneal epithelium, endothelium and stromal keratinocytes, lens epithelium, epithelial cells in the ciliary processes, aqueous humour and iris stromal cells. In the rat anterior segment, the highest cystatin C concentrations were found in the ciliary epithelium. Conclusions: Cystatin C is present in several cell types and is probably locally produced. The inhibitor is likely to be an important regulator of cysteine proteases in the retinal pigment epithelium, ciliary epithelium, aqueous humour, lens epithelium and in the corneal endothelium and epithelium

Cystatin C influences the autoimmune but not inflammatory response to cartilage type II collagen leading to chronic arthritis development

Introduction: Collagen-induced arthritis (CIA) is a mouse model for rheumatoid arthritis (RA) and is induced after immunization with type II collagen (CII). CIA, like RA, is an autoimmune disease leading to destruction of cartilage and joints, and both the priming and inflammatory phases have been suggested to be dependent on proteases. In particular, the cysteine proteases have been proposed to be detrimental to the arthritic process and even immunomodulatory. A natural inhibitor of cysteine proteases is cystatin C. Methods: Cystatin C-deficient, sufficient and heterozygous mice were tested for onset, incidence and severity of CIA. The effect of cystatin C-deficiency was further dissected by testing the inflammatory effector phase of CIA; that is, collagen antibody-induced arthritis model and priming phase, that is, T cell response both in vivo and in vitro. In addition, in order to determine the importance of T cells and antigen-presenting cells (APCs), these cell populations were separated and in vitro T cell responses determined in a mixed co-culture system. Finally, flow cytometry was used in order to further characterize cell populations in cystatin C-deficient mice. Results: Here, we show that mice lacking cystatin C, develop arthritis at a higher incidence and an earlier onset than wild-type controls. Interestingly, when the inflammatory phase of CIA was examined independently from immune priming then cystatin C-deficiency did not enhance the arthritis profile. However, in line with the enhanced CIA, there was an increased T cell and B cell response as delayed-type hypersensitivity reaction and anti-CII antibody titers were elevated in the cystatin C-deficient mice after immunization. In addition, the ex vivo naive APCs from cystatin C-deficient mice had a greater capacity to stimulate T cells. Interestingly, dendritic cells had a more activated phenotype in naive cystatin C-deficient mice. Conclusions: The lack of cystatin C enhances CIA and primarily affects in vivo priming of the immune system. Although the mechanism of this is still unknown, we show evidence for a more activated APC compartment, which would elevate the autoimmune response towards CII, thus resulting in an enhanced development of chronic arthritis

Analysis of spatial variability in hyperspectral imagery of the uterine cervix in vivo

The use of fluorescence and reflectance spectroscopy in the analysis of cervical histopathology is a growing field of research. The majority of this research is performed with point-like probes. Typically, clinicians select probe sites visually, collecting a handful of spectral samples. An exception to this methodology is the Hyperspectral Diagnostic Imaging (HSDI®) instrument developed by Science and Technology International. This non-invasive device collects contiguous hyperspectral images across the entire cervical portio. The high spatial and spectral resolution of the HSDI instruments make them uniquely well suited for addressing the issues of coupled spatial and spectral variability of tissues in vivo. Analysis of HSDI data indicates that tissue spectra vary from point to point, even within histopathologically homogeneous regions. This spectral variability exhibits both random and patterned components, implying that point monitoring may be susceptible to significant sources of noise and clutter inherent in the tissue. We have analyzed HSDI images from clinical CIN (cervical intraepithelial neoplasia) patients to quantify the spatial variability of fluorescence and reflectance spectra. This analysis shows the spatial structure of images to be fractal in nature, in both intensity and spectrum. These fractal tissue textures will limit the performance of any point-monitoring technology

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

ML, CD, IvL, GP, TM, SD, MS, APF, CT, DL, MAH, KL and SL: project grants from the Swedish Research Council, the Swedish Cancer Society and the Swedish Childhood Cancer Foundation. MHi and JC: Cancer Research UK (C8/A6613). MC, EP and WE: Wellcome Trust (073915). MN and BV: projects MEYS-NPS-LO1413 and GACR P206/12/G151. EMC, MP, MMS, ZF and PG: Norwegian Cancer Society (182735, 732200) and Helse Vest (911884, 911789). RB and SC: NIH (R01 CA95684), the Leukemia and Lymphoma Society and the Waxman Foundation. NW, AH, Ad’H: Cancer Research UK (C21383/A6950) and Engineering and Physical Sciences Research Council Doctoral Training Program. JL and YZ: Cancer Research UK (C240/A15751). MH and BW: SARomics Biostructures ABUY, KF: DDDP SciLife, Sweden. LJ, MHa, RS and A-LG: CBCS, Sweden. VP: SciLife fellowship. AT: Breast Cancer Research Scotland.The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.Publisher PDFPeer reviewe

A Frameshift Mutation in Golden Retriever Dogs with Progressive Retinal Atrophy Endorses SLC4A3 as a Candidate Gene for Human Retinal Degenerations

Progressive retinal atrophy (PRA) in dogs, the canine equivalent of retinitis pigmentosa (RP) in humans, is characterised by vision loss due to degeneration of the photoreceptor cells in the retina, eventually leading to complete blindness. It affects more than 100 dog breeds, and is caused by numerous mutations. RP affects 1 in 4000 people in the Western world and 70% of causal mutations remain unknown. Canine diseases are natural models for the study of human diseases and are becoming increasingly useful for the development of therapies in humans. One variant, prcd-PRA, only accounts for a small proportion of PRA cases in the Golden Retriever (GR) breed. Using genome-wide association with 27 cases and 19 controls we identified a novel PRA locus on CFA37 (praw = 1.94×10−10, pgenome = 1.0×10−5), where a 644 kb region was homozygous within cases. A frameshift mutation was identified in a solute carrier anion exchanger gene (SLC4A3) located within this region. This variant was present in 56% of PRA cases and 87% of obligate carriers, and displayed a recessive mode of inheritance with full penetrance within those lineages in which it segregated. Allele frequencies are approximately 4% in the UK, 6% in Sweden and 2% in France, but the variant has not been found in GRs from the US. A large proportion of cases (approximately 44%) remain unexplained, indicating that PRA in this breed is genetically heterogeneous and caused by at least three mutations. SLC4A3 is important for retinal function and has not previously been associated with spontaneously occurring retinal degenerations in any other species, including humans

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction