Exploiting knowledge of mesenchymal stromal cells in vivo for bone disease therapy development

This thesis aims to demonstrate how understanding of the nature of MSCs in vivo can be used to guide bone disease therapy development. It first address the unpredictable MSC content of bone marrow (BM) aspirates used for therapy; then examines MSC enrichment using clinical grade immunomagnetic cell selection. Induction of osteogenesis was subsequently explored; by examining an induced membrane (IM) used for bone regeneration. Finally the potential of a janus kinase (JAK) inhibitor to block osteogenesis was assessed, by studying its effect on MSCs in vitro. Flow cytometry was used to enumerate cells expressing a CD45-/low CD271+ phenotype in BM aspirate and this was compared to colony forming unit fibroblast (CFU-F) content. MSCs were enriched from BM, enzymatically treated femoral heads (FH) and intramedullary canal aspirates and enumerated. The composition morphology, MSC content and differentiation potential of IM was compared to periosteum. The potential effects of JAK inhibition on MSC colony formation, expansion and differentiation potential were examined. The concentration of cells expressing a CD45-/low CD271+ phenotype strongly correlated with CFU-F concentration (R=0.812, p<0.001). Immunomagnetic cell selection resulted in an increase in the proportion of MSCs in BM, FH and intramedullary canal aspirates by 204, 14.1 and 291-fold respectively. The regenerative potential of periosteum and IM were comparable. JAK inhibition did not affect MSC growth, osteogenesis or chondrogenesis but caused an increase in adipogenesis at concentrations ≥100nM compared to controls (1.38 fold, p=0.041). Flow cytometry may be used to rapidly and accurately predict the MSC content of BM. Clinical grade immunomagnetic selection can substantially increase the purity of MSCs from bone cavities. The similarity, in terms of regenerative potential, of periosteum and IM gives insight into its use for bone regeneration. JAK inhibition did not affect in vitro osteogenesis but has potential to affect in vivo osteogenesis through stimulation of adipogenesis

Are conservation actions reducing the threat to India's vulture populations?

Research Communications.-- et al.Veterinary use of the non-steroidal anti-inflammatory drug, diclofenac is responsible for the population collapse of resident vulture species in India. Conservation efforts, including a ban on veterinary diclofenac and the identification of a vulture-safe alternative (meloxicam), were introduced in 2006 in order to address the threat. Sampling of domesticated ungulate carcasses available to vultures in India was undertaken in three surveys prior to, around the time of, and 1-2 years after the ban in order to quantify the prevalence of diclofenac and meloxicam residues. A total of 1445, 1488 and 1251 liver tissue samples were collected from nine states and analysed with a validated LC-ESI/MS methodology. Overall diclofenac prevalence levels declined by almost a half over the three surveys, and there was an increase in meloxicam prevalence between the second and third surveys, although some states revealed little change. These surveys indicate that two of the key conservation actions to counter the threat faced by vultures - banning veterinary diclofenac and promoting meloxicam as a safe alternative - are beginning to take effect. However, because only a small proportion of diclofenac-contaminated carcasses is sufficient to cause vulture population declines, further efforts are needed to eliminate diclofenac from the food supply of India's vultures.The research was funded by the UK Government’s Darwin Initiative programme and by the Royal Society for the Protection of Birds, UK.Peer Reviewe

Climate-groundwater dynamics inferred from GRACE and the role of hydraulic memory

Groundwater is the largest store of freshwater on Earth after the cryosphere and provides a substantial proportion of the water used for domestic, irrigation and industrial purposes. Knowledge of this essential resource remains incomplete, in part, because of observational challenges of scale and accessibility. Here we examine a 14-year period (2002–2016) of GRACE observations to investigate climate-groundwater dynamics of 14 tropical and sub-tropical aquifers selected from WHYMAP's 37 large aquifer systems of the world. GRACE-derived changes in groundwater storage resolved using GRACE JPL Mascons and the CLM Land Surface Model are related to precipitation time series and regional-scale hydrogeology. We show that aquifers in dryland environments exhibit long-term hydraulic memory through a strong correlation between groundwater storage changes and annual precipitation anomalies integrated over the time series; aquifers in humid environments show short-term memory through strong correlation with monthly precipitation. This classification is consistent with estimates of Groundwater Response Times calculated from the hydrogeological properties of each system, with long (short) hydraulic memory associated with slow (rapid) response times. The results suggest that groundwater systems in dryland environments may be less sensitive to seasonal climate variability but vulnerable to long-term trends from which they will be slow to recover. In contrast, aquifers in humid regions may be more sensitive to seasonal climate disturbances such as ENSO-related drought but may also be relatively quick to recover. Exceptions to this general pattern are traced to human interventions through groundwater abstraction. Hydraulic memory is an important factor in the management of groundwater resources, particularly under climate change

Conservation efforts of Kihansi spray toad Nectophrynoides asperginis: its discovery, captive breeding, extinction in the wild and re-introduction

Species conservation depends on the initiatives to restore or retain and sustainably use the environment in which the species live. This paper highlights how development projects can affect biodiversity conservation and the challenges in achieving sustainable development. The paper discusses a case study of the Kihansi Spray Toad (KST) (Nectophrynoides asperginis) from its discovery, extinction in the wild, captive breeding and subsequent reintroduction to its native habitat; focusing on events, challenges, approaches in addressing issues, future prospects and achievements in the conservation of this endemic species. There has been considerable success in KST husbandry in captivity and reintroduction trials of the toad to the wild while concurrently the operations of the hydropower plant and the catchment ecosystem services have continued to provide electricity for domestic &amp; industrial development and support human livelihoods respectively. The paper underscores the importance of interdisciplinary approach in addressing conservation problems and the need for serious commitment of participating parties, but also on the need to balance conservation with sustainable development.Key words: Kihansi spray toad, extinction, reintroduction

AAC Viewfield Hard Red Spring Wheat

AAC Viewfield hard red spring wheat (Triticum aestivum L.) has grain yield significantly higher than the check cultivars Katepwa and Lillian and is similar to Carberry. AAC Viewfield matures significantly later than Katewpa and Lillian but is similar to Carberry. AAC Viewfield has an awned spike, a low lodging score indicative of strong straw, and significantly shorter plant stature than all checks. AAC Viewfield expressed resistance to prevalent races of yellow rust and stem rust, moderate resistance to leaf rust and common bunt, and intermediate resistance to Fusarium head blight. AAC Viewfield has quality attributes within the range of the check cultivars and is eligible for grades of Canada Western Red Spring

Highway deicing salt dynamic runoff to surface water and subsequent infiltration to groundwater during severe UK winters

Dynamic impact to the water environment of deicing salt application at a major highway (motorway) interchange in the UK is quantitatively evaluated for two recent severe UK winters. The contaminant transport pathway studied allowed controls on dynamic highway runoff and storm-sewer discharge to a receiving stream and its subsequent leakage to an underlying sandstone aquifer, including possible contribution to long-term chloride increases in supply wells, to be evaluated. Logged stream electrical-conductivity (EC) to estimate chloride concentrations, stream flow, climate and motorway salt application data were used to assess salt fate. Stream loading was responsive to salt applications and climate variability influencing salt release. Chloride (via EC) was predicted to exceed the stream Environmental Quality Standard (250 mg/l) for 33% and 18% of the two winters. Maximum stream concentrations (3500 mg/l, 15% sea water salinity) were ascribed to salt-induced melting and drainage of highway snowfall without dilution from, still frozen, catchment water. Salt persistance on the highway under dry-cold conditions was inferred from stream observations of delayed salt removal. Streambed and stream-loss data demonstrated chloride infiltration could occur to the underlying aquifer with mild and severe winter stream leakage estimated to account for 21 to 54% respectively of the 70 t of increased chloride (over baseline) annually abstracted by supply wells. Deicing salt infiltration lateral to the highway alongside other urban/natural sources were inferred to contribute the shortfall. Challenges in quantifying chloride mass/fluxes (flow gauge accuracy at high flows, salt loading from other roads, weaker chloride-EC correlation at low concentrations), may be largely overcome by modest investment in enhanced data acquisition or minor approach modification. The increased understanding of deicing salt dynamic loading to the water environment obtained is relevant to improved groundwater resource management, highway salt application practice, surface-water - ecosystem management, and decision making on highway drainage to ground

Management and Population Status of Kihansi Spray Toad Nectophrynoides asperginis in Captive Breeding Facilities in Tanzania

Kihansi spray toad Nectophrynoides asperginis was discovered in 1996 in Kihansi gorge. The toad was declared extinct in the wild in 2009 due to habitat alteration. Before its extinction, 499 individuals were flown to the United States of America zoos in 2000 for captive breeding. In 2010, the University of Dar es Salaam, and in 2011 the Kihansi captive breeding facilities were established in Tanzania. The intention was to breed, and reintroduce the toad back to the natural environment in the gorge. The founder populations for the two facilities were sourced from the USA zoos. This study addresses captive management practices, and population status of the toad at the two facilities from 2013 to 2019. Toad counts were carried out once every two months. There was a significant increase in the number of toads over the years. The increase was associated with suitable management practices. Success in captive breeding at the facilities led to the removal of 3,236 individuals from the University for restocking the Kihansi facility and for reintroduction, and 1,273 individuals from Kihansi facility for reintroduction. The establishment of the two facilities played a major role in both the ex-situ and in-situ conservation of the toadKeywords: Kihansi spray toad; extinction; captive breeding; population; reintroduction

Using globally threatened pelagic birds to identify priority sites for marine conservation in the South Atlantic Ocean

The Convention on Biological Diversity aspires to designate 10% of the global oceans as Marine Protected Areas (MPAs), but so far, few MPAs protect pelagic species in the high seas. Transparent scientific approaches are needed to ensure that these encompass areas with high biodiversity value. Here we used the distribution of all globally threatened seabirds breeding in a centrally located archipelago (Tristan da Cunha) to provide guidance on where MPAs could be established in the South Atlantic Ocean. We combined year-round tracking data from six species, and used the systematic conservation-planning tool, 'Zonation', to delineate areas that would protect the largest proportion of each population. The areas used most intensively varied among species and seasons. Combining the sites used by all six species suggested that the most important areas of the South Atlantic are located south of South Africa, around the central South Atlantic between 30 degrees S and 55 degrees S, and near South America. We estimated that the longline fishing effort in these intensively used areas is around 11 million hooks on average each year, highlighting the need for improved monitoring of seabird bycatch rates and the enforcement of compliance with bird bycatch mitigation requirements by fisheries. There was no overlap between the identified areas and any of the existing MPAs in the South Atlantic. The conservation of these highly mobile, pelagic species cannot be achieved by single countries, but requires a multi-national approach at an ocean-basin scale, such as an agreement for the conservation of biodiversity beyond national jurisdiction under the United Nation Convention on the Law of the Sea

A rapid biodiversity survey of Papua New Guinea's Manus and Mussau Islands

[Extract] Aim: The relatively remote islands of Manus and Mussau, located in the northern portion of the Bismark sea have been long identified as key biodiversity areas in Papua New Guinea and within greater Melanesia. Manus Island has long been known for its endemism and relatively intact forest, while Mussau Island, although relatively unstudied, has been recognised as an Endemic Bird Area. This report documents the findings of a series of rapid biodiversity surveys focusing on terrestrial flora and fauna, funded by the CEPF, encompassing four sites across the islands of Manus and Mussau; undertaken by a WCS led team of national and international taxonomic specialists in October 2014. The objective of these surveys was to investigate the biodiversity values of these areas. In conjunction with participatory community work conducted prior to, and following the surveys the wider WCS project aims to identify options for natural resource management in the region which addresses both community and biodiversity needs

Developing a topic-based repository of clinical trial individual patient data: experiences and lessons learned from a pilot project

BACKGROUND: Building a dataset of individual participant data (IPD) for meta-analysis represents considerable research investment as well as collaboration across multiple institutions and researchers. Making arrangements to curate and share the dataset beyond the IPD meta-analysis project for which it was established, for reuse in future research projects, would maximise the value of this investment. METHODS: Our aim was to establish the Cochrane repository for individual patient data from clinical trials in pregnancy and childbirth (CRIB) as an example of how an IPD repository could become part of Cochrane infrastructure. We believed that establishing CRIB under Cochrane auspices would engender trust and encourage trial investigators to share data, and at the same time position Cochrane to take steps towards expanding the number of reviews with IPD synthesis. RESULTS: CRIB was designed as a web-based platform to receive, host and facilitate onward sharing of de-identified data. Development was not straightforward and we did not fully achieve our aim as intended. We describe the challenges encountered and suggest ways that future repositories might overcome these. In particular, securing the legal agreements required to facilitate data sharing proved to be the main barrier, being time-consuming and more complex than anticipated. CONCLUSIONS: We would recommend that researchers conducting IPD meta-analysis should consider discussing the option to transfer the curated IPD datasets to a repository at the end of the initial meta-analysis and this should be recognised within the data sharing agreements made with the original data contributors