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Objectives: To assess the safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation (MAG200) in the treatment of knee osteoarthritis over 12 months. Design: A single-centre, double-blind, ascending dose, randomised controlled trial. 40 participants with moderate knee osteoarthritis were randomised to receive a single intra-articular injection of MAG200 (dose cohorts:10, 20, 50, 100 ​× ​106 ​cells) or placebo. Primary objectives were safety and efficacy according to a compound responder analysis of minimal clinically important difference in pain (numerical pain rating scale [NPRS]) and function (Knee Injury and Osteoarthritis Outcome Score - Function in Daily Living subscale [KOOSADL]) at month 12. Secondary efficacy outcomes included changes from baseline in patient reported outcome measures and evaluation of disease-modification using quantitative MRI. Results: Treatment was well tolerated with no treatment-related serious adverse events. MAG200 cohorts reported a greater proportion of responders than placebo and demonstrated clinical and statistically significant improvement in pain and clinically relevant improvement in all KOOS subscales. MAG200 demonstrated a reproducible treatment effect over placebo, which was clinically relevant for pain in the 10 ​× ​106 dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p ​= ​0.0468]) and for function in the 20 ​× ​106 and 100 ​× ​106 dose cohorts (mean difference KOOSADL:10.12[95%CI:-1.51,21.76, p ​= ​0.0863] and 10.81[95%CI:-1.42,23.04, p ​= ​0.0810] respectively). A trend in disease-modification was observed with improvement in total knee cartilage volume in MAG200 10, 20, and 100 ​× ​106 dose cohorts, with progression of osteoarthritis in placebo, though this was not statistically significant. No clear dose response was observed. Conclusion: This early-phase study provides supportive safety and efficacy evidence to progress MAG200 to later-stage trial development. Trial registration: ACTRN12617001095358/ACTRN12621000622808.

The landscape mosaic model quantifies and maps the spatial juxtaposition of different land uses. It provides a landscape perspective of anthropic threats posed by agriculture and urban development, and the spatial-temporal shifting of the landscape mosaic indicates landscapes where anthropic intensity has changed. We use the U.S. Geological Survey provided National Land Cover Database (NLCD) for the years 2001 and 2021 to derive the landscape mosaic at five analysis scales. To improve earlier implementations of the model, we introduce the heatmap, a flexible scheme providing more thematic reporting opportunities and allowing for better quantitative summary reporting across analysis scales as well as for temporal trends. The results are exemplified at regional scale for the Atlanta metropolitan area. We use the improved model to investigate the land cover context over time and at different analysis scales and show how custom color tables detail different thematic features of the landscape mosaic, including the degree and change of anthropic intensity. We conclude with a discussion of potential applications in ecology, landscape planning, and restoration to illustrate the benefits of the revised landscape mosaic model. All assessment tools are now available in open-source software packages.

The National Land Cover Database (NLCD), a product suite produced through the MultiResolution Land Characteristics (MRLC) consortium, is an operational land cover monitoring program. Starting from a base year of 2001, NLCD releases a land cover database every 2–3-years. The recent release of NLCD2019 extends the database to 18 years. We implemented a stratified random sample to collect land cover reference data for the 2016 and 2019 components of the NLCD2019 database at Level II and Level I of the classification hierarchy. For both dates, Level II land cover overall accuracies (OA) were 77.5% ± 1% (± value is the standard error) when agreement was defined as a match between the map label and primary reference label only, and increased to 87.1% ± 0.7% when agreement was defined as a match between the map label and either the primary or alternate reference label. At Level I of the classification hierarchy, land cover OA was 83.1% ± 0.9% for both 2016 and 2019 when agreement was defined as a match between the map label and primary reference label only, and increased to 90.3% ± 0.7% when agreement also included the alternate reference label. The Level II and Level I OA for the 2016 land cover in the NLCD2019 database were 5% higher compared to the 2016 land cover component of the NLCD2016 database when agreement was defined as a match between the map label and primary reference label only. No improvement was realized by the NLCD2019 database when agreement also included the alternate reference label. User’s accuracies (UA) for forest loss and grass gain were>70% when agreement included either the primary or alternate label, and UA was generally70% for grass loss and gain and water gain and generally

Aim: To evaluate safety and efficacy of low dose autologous adipose-derived mesenchymal stem cells (ADMSCs) for treatment of disc degeneration resulting in low back pain (LBP). Methods: Nine participants with chronic LBP originating from single-level lumbar disc disease underwent intradiscal injection of 10 million ADMSCs with optional repetition after 6 months. Results: No unexpected or serious adverse events were recorded. Seven (78%) of participants reported reductions in pain 12 months after treatment. Five (56%) reported increased work capacity. Three (33%) reduced analgesic medication. Improvements in EQ-5D and Oswestry disability index results were observed. MRI demonstrated no further disc degeneration and improvements to annular fissures and disc protrusions. Conclusion: This study provides initial evidence of safety and efficacy of ADMSCs for discogenic LBP.

BackgroundIntervention trials promoting physical activity among older people frequently report low and unrepresentative recruitment. Better understanding of reasons for participation can help improve recruitment. This study explored why participants enrolled in the Coaching for Healthy Ageing (CHAnGE) trial, including how their decision was influenced by recruitment strategies. CHAnGE was a cluster randomised controlled trial testing the effectiveness of a healthy ageing program targeting inactivity and falls. Seventy-two groups of people aged 60+ were recruited from community organisations via informal presentations by the health coaches.MethodsWe conducted a secondary thematic analysis of interview data from our wider qualitative evaluation in which 32 purposively sampled trial participants took part in semi-structured interviews about their experiences of CHAnGE. Data relating to recruitment and participation were analysed inductively to identify themes, then a coding framework comprising the core constructs from self-determination theory-autonomy, competence and relatedness-was used to explore if and how this theory fit with and helped to explain our data.ResultsRecruitment presentations promoted the CHAnGE intervention well in terms of addressing value expectations of structured support, different forms of accountability, credibility, achievability and, for some, a potential to enhance social relationships. Participation was motivated by the desire for improved health and decelerated ageing, altruism and curiosity. These factors related strongly to self-determination concepts of autonomy, competence and relatedness, but the intervention's demonstrated potential to support self-determination needs could be conveyed more effectively.ConclusionsFindings suggest that recruitment could have greater reach using: 1. Strengths-based messaging focusing on holistic gains, 2. Participant stories that highlight positive experiences, and 3. Peer support and information sharing to leverage altruism and curiosity. These theory-informed improvements will be used to increase participation in future trials, including people in hard-to-recruit groups. They may also inform other physical activity trials and community programs.

Acute respiratory distress syndrome (ARDS) is a condition of acute respiratory failure resulting from noncardiogenic pulmonary edema. It may occur as a consequence of lung infection, sepsis, trauma, aspiration or drug reaction. The pathogenesis of ARDS is understood to be an unregulated inflammatory cascade with both endothelial and epithelial layer damage leading to alveolar fluid collection and pulmonary edema. Despite improved understanding of the cause of ARDS, treatment remains supportive with a mortality rate ranging from 25–40%. Preclinical and early phase clinical trials have highlighted the potential role of mesenchymal stem cells in combating the inflammatory cascade through immunomodulatory mechanisms and assisting in tissue repair.

Abstract Background A prospective analysis of the effect of autologous adipose derived mesenchymal stem cell (MSC) therapy in the treatment of an osteochondral defect of the knee with early progressive osteoarthritis following unsuccessful surgical intervention of osteochondritis dissecans (OCD). Case presentation After failed conventional management of OCD a patient undergoes intra-articular MSC therapy. Patient outcome measures included the Numeric Pain Rating Scale (NPRS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Structural outcome was assessed using MRI with the novel technique of T2 mapping used to indicate cartilage quality. Following MSC therapy the patient reported improvement in pain and function as measured by NPRS, WOMAC and KOOS. Repeat MRI analysis showed regeneration of cartilage. MRI T2 mapping indicated hyaline like cartilage regrowth. Conclusion In this report, the use of MSCs, after unsuccessful conventional OCD management, resulted in structural, functional and pain improvement. These results highlight the need to further study the regenerative potential of MSC therapy. Trial registration Australian and New Zealand Clinical Trial Registry Number - ACTRN12615000258550 (Date registered 19/03/2015 – retrospectively registered).

The Multi-Resolution Land Characteristics (MRLC) Consortium demonstrates the national benefits of USA Federal collaboration. Starting in the mid-1990s as a small group with the straightforward goal of compiling a comprehensive national Landsat dataset that could be used to meet agencies’ needs, MRLC has grown into a group of 10 USA Federal Agencies that coordinate the production of five different products, including the National Land Cover Database (NLCD), the Coastal Change Analysis Program (C-CAP), the Cropland Data Layer (CDL), the Gap Analysis Program (GAP), and the Landscape Fire and Resource Management Planning Tools (LANDFIRE). As a set, the products include almost every aspect of land cover from impervious surface to detailed crop and vegetation types to fire fuel classes. Some products can be used for land cover change assessments because they cover multiple time periods. The MRLC Consortium has become a collaborative forum, where members share research, methodological approaches, and data to produce products using established protocols, and we believe it is a model for the production of integrated land cover products at national to continental scales. We provide a brief overview of each of the main products produced by MRLC and examples of how each product has been used. We follow that with a discussion of the impact of the MRLC program and a brief overview of future plans.

Publicly owned public transport contributed to the distinctive character of 20th century European cities. Today, however, the sector is being opened up to various forms of competition. Using a comparative study of urban public transport in six European countries, this paper traces the emergence of a new European mode of regulation for the sector. This new framework has not, however, always led to a deterioration in wages or working conditions, since national employment systems remain important. Change has often been justified as leading to improved service quality: traditional public sector employment, above all job security, was seen as contributing to bad service for passengers. Our study, undertaken as part of the EU-funded Dynamo project, however finds no such simple link — either negative or positive — between the quality of service and the nature of employment.

Monitoring and quantifying changes in vegetation cover over large areas using remote sensing can be achieved using the Normalized Difference Vegetation Index (NDVI), an indicator of greenness. However, distinguishing gradual shifts in NDVI (e.g., climate related-changes) versus direct and rapid changes (e.g., fire, land development) is challenging as changes can be confounded by time-dependent patterns, and variation associated with climatic factors. In the present study, we leveraged a method that we previously developed for a pilot study to address these confounding factors by evaluating NDVI change using autoregression techniques that compare results from univariate (NDVI vs. time) and multivariate analyses (NDVI vs. time and climatic factors) for 7,660,636 1 km × 1 km pixels comprising the 48 contiguous states of the USA, over a 25-year period (1989–2013). NDVI changed significantly for 48% of the nation over the 25-year period in the univariate analyses where most significant trends (85%) indicated an increase in greenness over time. By including climatic factors in the multivariate analyses of NDVI over time, the detection of significant NDVI trends increased to 53% (an increase of 5%). Comparisons of univariate and multivariate analyses for each pixel showed that less than 4% of the pixels had a significant NDVI trend attributable to gradual climatic changes while the remainder of pixels with a significant NDVI trend indicated that changes were due to direct factors. While most NDVI changes were attributable to direct factors like wildfires, drought or flooding of agriculture, and tree mortality associated with insect infestation, these conditions may be indirectly influenced by changes in climatic factors.

The question of incorporating road maps into U.S. national assessments of forest fragmentation has been a contentious issue, but there has not been a comparative national analysis to inform the debate. Using data and indices from previous national assessments, we compared fragmentation as calculated from high-resolution land-cover maps alone (Method 1) and after superimposing detailed road maps (Method 2). There was more overall fragmentation with Method 2. However, because roads were often adjacent to other nonforest land cover, Method 1 typically detected > 80% of the forest edge and > 88% of the fragmentation of core, i.e., intact, forest that was detected by Method 2. Indices based on individual patch size changed much more for Method 2; for example, area-weighted average patch size was typically 50-90% smaller. The relative geographic distribution of core forest was the same for both methods. Our results emphasize that the question of incorporating road maps must consider the purpose of the assessment, the characteristics of the data, and the relative sensitivities of indices to different patterns of fragmentation. As a practical matter, unless road-caused fragmentation is of special interest, land-cover maps alone may provide an adequate representation of the geography of forest fragmentation.