The effect of Me2SO overexposure during cryopreservation on HOS TE85 and hMSC viability, growth and quality

With the cell therapy industry continuing to grow, the ability to preserve clinical grade cells, including mesenchymal stem cells (MSCs), whilst retaining cell viability and function remains critical for the generation of off-the-shelf therapies. Cryopreservation of MSCs, using slow freezing, is an established process at lab scale. However, the cytotoxicity of cryoprotectants, like Me2SO, raises questions about the impact of prolonged cell exposure to cryoprotectant at temperatures >0 °C during processing of large cell batches for allogenic therapies prior to rapid cooling in a controlled rate freezer or in the clinic prior to administration. Here we show that exposure of human bone marrow derived MSCs to Me2SO for ≥1 h before freezing, or after thawing, degrades membrane integrity, short-term cell attachment efficiency and alters cell immunophenotype. After 2 h's exposure to Me2SO at 37 °C post-thaw, membrane integrity dropped to ∼70% and only ∼50% of cells retained the ability to adhere to tissue culture plastic. Furthermore, only 70% of the recovered MSCs retained an immunophenotype consistent with the ISCT minimal criteria after exposure. We also saw a similar loss of membrane integrity and attachment efficiency after exposing osteoblast (HOS TE85) cells to Me2SO before, and after, cryopreservation. Overall, these results show that freezing medium exposure is a critical determinant of product quality as process scale increases. Defining and reporting cell sensitivity to freezing medium exposure, both before and after cryopreservation, enables a fair judgement of how scalable a particular cryopreservation process can be, and consequently whether the therapy has commercial feasibility.

The Hurst exponent as an indicator of the behaviour of a model monopile in an ocean wave testing basin

With the importance of renewable energy well-established worldwide, and targets of such energy quantified in many cases, there exists a considerable interest in the assessment of wind and wave devices. While the individual components of these devices are often relatively well understood and the aspects of energy generation well researched, there seems to be a gap in the understanding of these devices as a whole and especially in the field of their dynamic responses under operational conditions. The mathematical modelling and estimation of their dynamic responses are more evolved but research directed towards testing of these devices still requires significant attention. Model-free indicators of the dynamic responses of these devices are important since it reflects the as-deployed behaviour of the devices when the exposure conditions are scaled reasonably correctly, along with the structural dimensions. This paper demonstrates how the Hurst exponent of the dynamic responses of a monopile exposed to different exposure conditions in an ocean wave basin can be used as a model-free indicator of various responses. The scaled model is exposed to Froude scaled waves and tested under different exposure conditions. The analysis and interpretation is carried out in a model-free and output-only environment, with only some preliminary ideas regarding the input of the system. The analysis indicates how the Hurst exponent can be an interesting descriptor to compare and contrast various scenarios of dynamic response conditions.

Development and Testing of the Elderly Social Vulnerability Index (ESVI): A Composite Indicator to Measure Social Vulnerability in the Jamaican Elderly Population

Over the last two decades social vulnerability has emerged as a major area of study, with increasing attention to the study of vulnerable populations. Generally, the elderly are among the most vulnerable members of any society, and widespread population aging has led to greater focus on elderly vulnerability. However, the absence of a valid and practical measure constrains the ability of policy-makers to address this issue in a comprehensive way. This study developed a composite indicator, The Elderly Social Vulnerability Index (ESVI), and used it to undertake a comparative analysis of the availability of support for elderly Jamaicans based on their access to human, material and social resources. The results of the ESVI indicated that while the elderly are more vulnerable overall, certain segments of the population appear to be at greater risk. Females had consistently lower scores than males, and the oldest-old had the highest scores of all groups of older persons. Vulnerability scores also varied according to place of residence, with more rural parishes having higher scores than their urban counterparts. These findings support the political economy framework which locates disadvantage in old age within political and ideological structures. The findings also point to the pervasiveness and persistence of gender inequality as argued by feminist theories of aging. Based on the results of the study it is clear that there is a need for policies that target specific population segments, in addition to universal policies that could make the experience of old age less challenging for the majority of older persons. Overall, the ESVI has displayed usefulness as a tool for theoretical analysis and demonstrated its potential as a policy instrument to assist decision-makers in determining where to target their efforts as they seek to address the issue of social vulnerability in old age. Data for this study came from the 2001 population and housing census of Jamaica, with multiple imputation for missing data. The index was derived from the linear aggregation of three equally weighted domains, comprised of eleven unweighted indicators which were normalized using z-scores. Indicators were selected based on theoretical relevance and data availability.

Climate change and the long-term viability of the World’s busiest heavy haul ice road

Climate models project that the northern high latitudes will warm at a rate in excess of the global mean. This will pose severe problems for Arctic and sub-Arctic infrastructure dependent on maintaining low temperatures for structural integrity. This is the case for the economically important Tibbitt to Contwoyto Winter Road (TCWR)—the world’s busiest heavy haul ice road, spanning 400 km across mostly frozen lakes within the Northwest Territories of Canada. In this study, future climate scenarios are developed for the region using statistical downscaling methods. In addition, changes in lake ice thickness are projected based on historical relationships between measured ice thickness and air temperatures. These projections are used to infer the theoretical operational dates of the TCWR based on weight limits for trucks on the ice. Results across three climate models driven by four RCPs reveal a considerable warming trend over the coming decades. Projected changes in ice thickness reveal a trend towards thinner lake ice and a reduced time window when lake ice is at sufficient thickness to support trucks on the ice road, driven by increasing future temperatures. Given the uncertainties inherent in climate modelling and the resultant projections, caution should be exercised in interpreting the magnitude of these scenarios. More certain is the direction of change, with a clear trend towards winter warming that will reduce the operation time window of the TCWR. This illustrates the need for planners and policymakers to consider future changes in climate when planning annual haulage along the TCWR.

Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability

Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer. Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer. Amongst 700 genes displaying reciprocal expression patterns we observed a significant enrichment in the cellular process glycosylation. Of 31 reciprocally-regulated glycosylation enzymes, a set of 8 (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3) were significantly up-regulated in clinical prostate carcinoma. Androgen exposure stimulated synthesis of glycan structures downstream of this core set of regulated enzymes including sialyl-Tn (sTn), sialyl Lewis(X) (SLe(X)), O-GlcNAc and chondroitin sulphate, suggesting androgen regulation of the core set of enzymes controls key steps in glycan synthesis. Expression of each of these enzymes also contributed to prostate cancer cell viability. This study identifies glycosylation as a global target for androgen control, and suggests loss of specific glycosylation enzymes might contribute to tumour regression following androgen depletion therapy.

Correlation between the photocatalysed oxidation of methylene blue in solution and the reduction of resazurin in a photocatalyst activity indicator ink (Rz Paii)

Assessment of Activity of 'Transparent and Clear' and 'Opaque and Highly Coloured' Photocatalytic Samples using a Fluorescent Photocatalytic Activity Indicator Ink, FPaii.

The photocatalytic activity of self-cleaning glass is assessed using a resazurin (Rz) photocatalyst activity indicator ink, i.e. Rz paii, via both the rate of change in the colour of the ink (blue to pink), R(Abs), and the rate of change in the fluorescence intensity, R(Fl), (λ(excitation) = 593 nm; λ(emission) = 639 nm) of the ink. In both cases the kinetics are zero order. Additional work with a range of glass samples of different photocatalytic activity reveal R(Abs) is directly related to R(Fl), thereby showing that the latter, like the former, can be used to provide a measure of the photocatalytic activity of the sample under test. The measured value of R(Fl) is found to be the same for 5 pieces of, otherwise identical, selfcleaning glass with: black, red, blue, yellow and no coloured tape stuck to their backs, which demonstrates that R(Fl) measurements can be used to measure photocatalytic activity under conditions of high colour and opacity under which R(Abs) cannot be measured. The relevance of this novel, fluorescence-based paii to the assessment of the activity of highly coloured, opaque photocatalytic samples, such as paints and tiles, is discussed briefly.

UK consensus project on quality in palliative day services: developing a quality indicator set using the RAND/UCLA appropriateness method

Introduction
Evaluating quality of palliative day services is essential for assessing care across diverse settings, and for monitoring quality improvement approaches.

Aim
To develop a set of quality indicators for assessment of all aspects (structure, process and outcome) of care in palliative day services.

Methods
Using a modified version of the RAND/UCLA appropriateness method (Fitch et al., 2001), a multidisciplinary panel of 16 experts independently completed a survey rating the appropriateness of 182 potential quality indicators previously identified during a systematic evidence review. Panel members then attended a one day, face-to-face meeting where indicators were discussed and subsequently re-rated. Panel members were also asked to rate the feasibility and necessity of measuring each indicator.

Results
71 indicators classified as inappropriate during the survey were removed based on median appropriateness ratings and level of agreement. Following the panel discussions, a further 60 were removed based on appropriateness and feasibility ratings, level of agreement and assessment of necessity. Themes identified during the panel discussion and findings of the evidence review were used to translate the remaining 51 indicators into a final set of 27.

Conclusion
The final indicator set included information on rationale and supporting evidence, methods of assessment, risk adjustment, and recommended performance levels. Further implementation work will test the suitability of this ‘toolkit’ for measurement and benchmarking. The final indicator set provides the basis for standardised assessment of quality across services, including care delivered in community and primary care settings.

Reference

• Fitch K, Bernstein SJ, Aguilar MD, et al. The RAND/UCLA Appropriateness Method User’s Manual. Santa Monica, CA: RAND Corporation; 2001. http://www.rand.org/pubs/monograph_reports/MR1269

The Acridian plagues, a new Holocene and Pleistocene palaeoclimatic indicator

[EN] Five palaeosols, intercalated within the Quaternary dune beds of Fuerteventura and Lanzarote (Canary Islands), off the Moroccan coast, mark wetter climatic episodes. In all of them, billions of calcified insect ootheca testify to past occurrences of Acridian plagues, such as those reaching the western Sahara following heavy rainfall events over the Sahel.

Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viability

It was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours.

The IJK Ride Indicator, 1976

State highway engineers realized a need for a numerical quality index and began planning for a research project of this type in 1951. The Present Serviceability Index was developed through the AASHO (now AASHTO) Road Test near Ottawa, Illinois, from 1956 to 1962.1 longitudinal profile and physical deterioration such as cracking, patching, and rut depth (for flexible pavements) were considered in deriving these Present Serviceability Index (PSI) equations

Validation Française de l’Échelle de la Personnalité Temporelle (French Validation of the Time Personality Indicator)

RÉSUMÉ Certains auteurs ont développé un intérêt pour la compréhension des aptitudes associées à la gestion du temps. Ainsi, plusieurs définitions théoriques ont été proposées afin de mieux cerner ce concept et une multitude de questionnaires a été développée afin de le mesurer. La présente étude visait à valider la traduction française d’un de ces outils, soit le Time Personality Indicator (TPI). Des analyses exploratoires et confirmatoires ont été effectuées sur l’ensemble des données recueillies auprès de 1 267 étudiants et employés de l’Université Laval ayant complété la version française du TPI ainsi que d’autres mesures de la personnalité. Les résultats ont révélé qu’une solution à huit facteurs permet de mieux décrire les données de l’échantillon. La discussion présente les raisons pour lesquelles la version française du TPI est valide, identifie certaines limites de la présente étude et souligne l’utilité de cet outil pour la recherche sur la gestion du temps. (ABSTRACT: Numerous authors have developed an interest towards the understanding of the abilities related to time management. As a consequence, multiple theoretical definitions have been proposed to explain time management. Likewise, several questionnaires have been developed in order to measure this concept. The aim of this study was to validate a French version of one of these tools, namely the Time Personality Indicator (TPI). The French version of the TPI and other personality questionnaires were completed by 1267 students and employees of Université Laval. The statistical approach used included exploratory and confirmatory analyses. Results revealed that an eight factor model provided a better adjustment to the data. The discussion provides arguments supporting the validity of the French version of the TPI and underlines the importance of such a tool for the research on time management)