ECONOMIC IMPACTS OF CHEMICAL USE REDUCTION ON THE SOUTH: DISCUSSION

Environmental Economics and Policy,

Explicating the challenges of providing novel media experiences driven by user personal data

The turn towards personal data to drive novel media experiences has resulted in a shift in the priorities and challenges associated with media creation and dissemination. This paper takes up the challenge of explicating this novel and dynamic scenario through an interview study of employees delivering diverse personal data driven media services within a large U.K. based media organisation. The results identify a need for better interactions in the user-data-service ecosystem where trust and value are prioritised and balanced. Being legally compliant and going beyond just the mandatory to further ensure social accountability and ethical responsibility as an organisation are unpacked as methods to achieve this balance in data centric interactions. The work also presents how technology is seen and used as a solution for overcoming challenges and realising priorities to provide value while preserving trust within the personal data ecosystem

Strategic responses to global challenges: The case of European banking, 1973–2000

In applying a strategy, structure, ownership and performance (SSOP) framework to three major clearing banks (ABN AMRO, UBS, Barclays), this article debates whether the conclusions generated by Whittington and Mayer about European manufacturing industry can be applied to the financial services sector. While European integration plays a key role in determining strategy, it is clear that global factors were far more important in determining management actions, leading to significant differences in structural adaptation. The article also debates whether this has led to improved performance, given the problems experienced with both geographical dispersion and diversification, bringing into question the quality of decision-making over the long term

Do Bat Gantries and Underpasses Help Bats Cross Roads Safely?

Major roads can reduce bat abundance and diversity over considerable distances. To mitigate against these effects and comply with environmental law, many European countries install bridges, gantries or underpasses to make roads permeable and safer to cross. However, through lack of appropriate monitoring, there is little evidence to support their effectiveness. Three underpasses and four bat gantries were investigated in northern England. Echolocation call recordings and observations were used to determine the number of bats using underpasses in preference to crossing the road above, and the height at which bats crossed. At gantries, proximity to the gantry and height of crossing bats were measured. Data were compared to those from adjacent, severed commuting routes that had no crossing structure. At one underpass 96% of bats flew through it in preference to crossing the road. This underpass was located on a pre-construction commuting route that allowed bats to pass without changing flight height or direction. At two underpasses attempts to divert bats from their original commuting routes were unsuccessful and bats crossed the road at the height of passing vehicles. Underpasses have the potential to allow bats to cross roads safely if built on pre-construction commuting routes. Bat gantries were ineffective and used by a very small proportion of bats, even up to nine years after construction. Most bats near gantries crossed roads along severed, pre-construction commuting routes at heights that put them in the path of vehicles. Crossing height was strongly correlated with verge height, suggesting that elevated verges may have some value in mitigation, but increased flight height may be at the cost of reduced permeability. Green bridges should be explored as an alternative form of mitigation. Robust monitoring is essential to assess objectively the case for mitigation and to ensure effective mitigation

Extreme Evolutionary Disparities Seen in Positive Selection across Seven Complex Diseases

Positive selection is known to occur when the environment that an organism inhabits is suddenly altered, as is the case across recent human history. Genome-wide association studies (GWASs) have successfully illuminated disease-associated variation. However, whether human evolution is heading towards or away from disease susceptibility in general remains an open question. The genetic-basis of common complex disease may partially be caused by positive selection events, which simultaneously increased fitness and susceptibility to disease. We analyze seven diseases studied by the Wellcome Trust Case Control Consortium to compare evidence for selection at every locus associated with disease. We take a large set of the most strongly associated SNPs in each GWA study in order to capture more hidden associations at the cost of introducing false positives into our analysis. We then search for signs of positive selection in this inclusive set of SNPs. There are striking differences between the seven studied diseases. We find alleles increasing susceptibility to Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), and Crohn's Disease (CD) underwent recent positive selection. There is more selection in alleles increasing, rather than decreasing, susceptibility to T1D. In the 80 SNPs most associated with T1D (p-value <7.01×10−5) showing strong signs of positive selection, 58 alleles associated with disease susceptibility show signs of positive selection, while only 22 associated with disease protection show signs of positive selection. Alleles increasing susceptibility to RA are under selection as well. In contrast, selection in SNPs associated with CD favors protective alleles. These results inform the current understanding of disease etiology, shed light on potential benefits associated with the genetic-basis of disease, and aid in the efforts to identify causal genetic factors underlying complex disease

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.</p

Serum S100A6 Concentration Predicts Peritoneal Tumor Burden in Mice with Epithelial Ovarian Cancer and Is Associated with Advanced Stage in Patients

BACKGROUND:Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival. METHODOLOGY AND PRINCIPAL FINDINGS:Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease. CONCLUSIONS:S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian cancer, when used in concert with other biomarkers