Response of glacier flow and structure to proglacial lake development and climate at Fjallsjökull, south-east Iceland

ABSTRACTOver recent decades, the number of outlet glaciers terminating in lakes in Iceland has increased in line with climate warming. The mass-balance changes of these lake-terminating outlet glaciers are sensitive to rising air temperatures, due to altered glacier dynamics and increased surface melt. This study aims to better understand the relationship between proglacial lake development, climate, glacier dynamics and glacier structure at Fjallsjökull, a large, lake-terminating outlet glacier in south-east Iceland. We used satellite imagery to map glacier terminus position and lake extent between 1973 and 2016, and a combination of aerial and satellite imagery to map the structural architecture of the glacier's terminus in 1982, 1994 and 2011. The temporal evolution of ice surface velocities between 1990 and 2018 was calculated using feature tracking. Statistically significant increases in the rate of terminus retreat and lake expansion were identified in 2001, 2009 and 2011. Our surface velocity and structural datasets revealed the development of localised flow ‘corridors’ over time, which conveyed relatively faster flow towards the glacier's terminus. We attribute the overall changes in dynamics and structural architecture at Fjallsjökull to rising air temperatures, but argue that the spatial complexities are driven by glacier specific factors, such as basal topography.</jats:p

Designing a Predictive Coding System for Electronic Discovery

Not long ago, the concept of using predictive coding and other technologies to assist with the electronic discovery process seemed revolutionary. Da Silva Moore and Global Aerospace stand as the first major cases where judges strongly supported predictive coding.1-2 A recent Indiana case recognized it as a useful method for reducing the amount of potentially relevant evidence that has to be searched and culled.3 Within just a few short years, using predictive coding as part of an electronic discovery process is now considered acceptable and perhaps even expected. It is not difficult to appreciate the advantages of predictive coding and its superiority over a manual process at various steps of electronic discovery, particularly during the review step.4-11 However, questions still remain about the efficacy of the predictive coding process and the tools that are available.12-13 Because the use of predictive coding systems in law is still in its infancy, it presents us with an opportunity to design something that will not only take advantage of the power of big data and computational algorithms, but that will also incorporate design and usability principles to provide an attractive and easy-to-use interface for lawyers to interact with. Predictive coding uses natural language processing and other mathematical models to enhance search results, but the essence of these systems is that they actually learn and the precision of the retrieval improves as additional collections of evidence are entered. Behind-the-scenes will be a repository where all of the evidence for a case resides. Our system will assist the lawyers in reducing the time and cost of an electronic discovery process as well as minimize the chances for mistakes in determining which evidence is relevant to a case and which evidence can be withheld under attorney-client privilege, as attorney work-product or another confidentiality doctrine. 1. Da Silva Moore v. Publicis Groupe & MSL Group, No. 11 Civ. 1279, 2012 WL 607412 (ALC) (AJP) (S.D.N.Y. Feb. 24, 2012). 2. Global Aerospace, Inc. v. Landow Aviation, L.P., No. CL 61040 (Vir. Cir. Ct. Apr. 23, 2012). 3. In re Biomet, 2013 WL 1729682 (N.D. Ind. Apr. 18, 2013). 4. Alison Silverstein and Geoffrey Vance. E-Discovery Myth Busters: Why Predictive Coding is Safe, Successful and Smart. Peer to Peer, Vol. 29, No. 4, December 2013, pp. 66-69. 5. John Papageorge. Predictive Coding Gaining Support in Courts. Indiana Lawyer, January 29-February 11, 2014, p. 8. 6. Adam M. Acosta. Predictive Coding: The Beginning of a New E-Discovery Era. Res Gestae, October 2012, pp. 8-14. 7. Ajith (AJ) Samuel. Analytics Driving the E-Discovery Process. Peer to Peer, Vol. 28, No. 2, June 2012. 8. Richard Acello. Beyond Prediction: Technology-Assisted Review Enters the Lexicon. ABA Journal, August 2012, pp. 37, 70. 9. Barry Murphy. The Rise of Technology-Assisted Review (TAR). Peer to Peer, Vol. 28, No. 2, June 2012, pp. 10. Brian Ingram. Controlling E-Discovery Costs in a Big Data World. Peer to Peer, Vol. 29, No. 1, March 2013. 11. Hal Marcus and Susan Stone. Beyond Predictive Coding - The True Power of Data Analytics [webinar]. International Legal Technology Association, May 19, 2015. 12. Jessica Watts and Gareth Evans. Predictive Coding in the Real World [webinar]. International Legal Technology Association, August 5, 2015. 13. Danielle Bethea. Predictive Coding: Revolutionizing Review or Still Gaining Momentum? Litigation and Practice Support: ITLA White Paper, International Legal Technology Association, June 2014

Could clinical photochemical internalisation be optimised to avoid neuronal toxicity?

Photochemical Internalisation (PCI) is a novel drug delivery technology in which low dose photodynamic therapy (PDT) can selectively rupture endo/lysosomes by light activation of membrane-incorporated photosensitisers, facilitating intracellular drug release in the treatment of cancer. For PCI to be developed further, it is important to understand whether nerve damage is an impending side effect when treating cancers within or adjacent to nervous system tissue. Dorsal root ganglion (DRG) neurons and their associated satellite glia were subjected to PCI treatment in a 3D co-culture system following incubation with photosensitisers: meso-tetraphenylporphine (TPPS2a) or tetraphenylchlorin disulfonate (TPCS2a) and Bleomycin. Results from the use of 3D co-culture models demonstrate that a cancer cell line PCI30 and satellite glia were more sensitive to PCI than neurons and mixed glial cells, athough neurite length was affected. Neurons in culture survived PCI treatment under conditions sufficient to kill tumour cells, suggesting cancers within or adjacent to nervous system tissue could be treated with this novel technology

Microscopic biophysical model of self-organization in tissue due to feedback between cell- and macroscopic-scale forces

We develop a microscopic biophysical model for self-organization and reshaping of artificial tissue, that is codriven by microscopic active forces between cells and an extracellular matrix (ECM), and macroscopic forces that develop within the tissue, finding close agreement with experiment. Microscopic active forces are stimulated by μ m -scale interactions between cells and the ECM within which they exist, and when large numbers of cells act together these forces drive, and are affected by, macroscopic-scale self-organization and reshaping of tissues in a feedback loop. To understand this loop, there is a need to (1) construct microscopic biophysical models that can simulate these processes for the very large number of cells found in tissues, (2) validate and calibrate those models against experimental data, and (3) understand the active feedback between cells and the extracellular matrix, and its relationship to macroscopic self-organization and reshaping of tissue. Our microscopic biophysical model consists of a contractile network representing the ECM, that interacts with a large number of cells via dipole forces, to describe macroscopic self-organization and reshaping of tissue. We solve the model using simulated annealing, finding close agreement with experiments on artificial neural tissue. We discuss the calibration of model parameters. We conclude that feedback between microscopic cell-ECM dipole interactions and tissue-scale forces is a key factor in driving macroscopic self-organization and reshaping of tissue. We discuss the application of the biophysical model to the simulation and rational design of artificial tissues

Dexamethasone treatment of pregnant F0 mice leads to parent of origin-specific changes in placental function of the F2 generation.

Dexamethasone treatment of F0 pregnant rodents alters F1 placental function and adult cardiometabolic phenotype. The adult phenotype is transmitted to the F2 generation without further intervention, but whether F2 placental function is altered by F0 dexamethasone treatment remains unknown. In the present study, F0 mice were untreated or received dexamethasone (0.2µgg(-1)day(-1), s.c.) over Days 11-15 or 14-18 of pregnancy (term Day 21). Depending on the period of F0 dexamethasone treatment, F1 offspring were lighter at birth or grew more slowly until weaning (P<0.05). Glucose tolerance (1gkg(-1), i.p.) of adult F1 males was abnormal. Mating F1 males exposed prenatally to dexamethasone with untreated females had no effect on F2 placental function on Day 19 of pregnancy. In contrast, when F1 females were mated with untreated males, F2 placental clearance of the amino acid analogue (14)C-methylaminoisobutyric acid was increased by 75% on Day 19 specifically in dams prenatally exposed to dexamethasone on Days 14-18 (P<0.05). Maternal plasma corticosterone was also increased, but F2 placental Slc38a4 expression was decreased in these dams (P<0.05). F0 dexamethasone treatment had no effect on F2 fetal or placental weights, regardless of lineage. Therefore, the effects of F0 dexamethasone exposure are transmitted intergenerationally to the F2 placenta via the maternal, but not paternal, line.This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1071/RD14285

Adapting tissue-engineered in vitro CNS models for high-throughput study of neurodegeneration

Neurodegenerative conditions remain difficult to treat, with the continuing failure to see therapeutic research successfully advance to clinical trials. One of the obstacles that must be overcome is to develop enhanced models of disease. Tissue engineering techniques enable us to create organised artificial central nervous system tissue that has the potential to improve the drug development process. This study presents a replicable model of neurodegenerative pathology through the use of engineered neural tissue co-cultures that can incorporate cells from various sources and allow degeneration and protection of neurons to be observed easily and measured, following exposure to neurotoxic compounds - okadaic acid and 1-methyl-4-phenylpyridinium. Furthermore, the technology has been miniaturised through development of a mould with 6 mm length that recreates the advantageous features of engineered neural tissue co-cultures at a scale suitable for commercial research and development. Integration of human-derived induced pluripotent stem cells aids more accurate modelling of human diseases, creating new possibilities for engineered neural tissue co-cultures and their use in drug screening

Methodological and economic evaluations of seven survey modes applied to health service research

Objective: To evaluate methodological outcomes and cost-effectiveness of seven survey modes, using a study of general public views towards pharmacy public health services. Methods: A cross-sectional survey was conducted in North West England among people aged =?18 years, using two approaches. Three interviewer-assisted modes were street, door-to-door and telephone. Four self-completion modes were single-and double-mailing to residential addresses, surveys sent to public/private business by post (postal-business), and questionnaires dropped-off at venues (drop-off). The study compared response rates, demographics and two domains ((a) actual use of and (b) willingness to use pharmacy public health services) between modes. Incremental cost-effectiveness ratios of different modes were assessed against the single-mailing. Key findings: Response rate varied between 5.1% (postal-business) and 34.5% (street). Respondent age, education, employment, socioeconomic and deprivation status varied between different modes. Results for domain (a) were similar for all modes. Interviewer-assisted modes resulted in more positive views on willingness to use advisory services (P < 0.05). The drop-off mode saved ?45.92 (US$72.55) per 1% increase in response rate compared to single mailing, while interviewer-assisted and double-mailing were more costly. At higher response rates, cost-savings by the drop-off mode diminished, but for other survey modes, additional costs decreased. Conclusion: Drop-off mode is cost-effective compared to the standard single mailing, but selection bias is possible. Street surveys are also an efficient method, but may carry a higher risk of social desirability bias. Mixed-modes surveys may reach wider sectors of the population. The similarity in use of services suggests all survey modes reach members of the public relevant to pharmacy researchers