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Ecosystems are often resilient enough to fully recover following a natural disturbance, or to transform into a new equilibrium favourable to the surrounding flora and fauna. However, at a local level, whether this transformation will be beneficial or not depends strongly on the level of disturbance and the available mechanisms for recovery. The Arctic, however, provides a potentially extreme environment for microbial growth and this is reflected in the microbial biodiversity, the in-situ growth rates, the biogeochemical cycling and its sensitivity to environmental change. In this study, we evaluated the current microbial biodiversity and environmental conditions around the landfill site in Adventdalen, Svalbard to identify differences across bacterial communities that might promote or accelerate naturally occurring environmental recovery. Landfill sites can induce changes in the local environment through the input of exogenous chemicals (both organic and inorganic) and microorganisms. Leachate can flow with run-off from the primary location of the landfill site due to rain, snow or ice melt and spread material into soils surrounding the site. In this study we found a strong effect of the landfill site on the bacterial diversity in the local landscape. Intervention is highly desirable to enhance the environment and improve the restoration by subtly altering the conditions at the site (such as the pH or drainage courses) and by encouraging specific groups of naturally occurring indigenous microorganisms to bioremediate the site.

Patient-derived xenograft (PDX) models involve the engraftment of tumour tissue in immunocompromised mice and represent an important pre-clinixtcal oncology research. A limitation of non-small cell lung cancer (NSCLC) PDX model derivation in NOD-scidIL2Rgammanull(NSG) mice is that a subset of initial engraftments are of lymphocytic, rather than tumour origin. In the lung TRACERx PDX pipeline, lymphoproliferations occurred in 17.8% of lung adenocarcinoma and 10% of lung squamous cell carcinoma transplantations, despite none of these patients having a prior or subsequent clinical history of lymphoproliferative disease. Lymphoproliferations were predominantly human CD20+ B cells and had the immunophenotype expected for post-transplantation diffuse large B cell lymphoma. All lymphoproliferations expressed Epstein-Barr-encoded RNAs (EBER). Analysis of immunoglobulin light chain gene rearrangements in three tumours where multiple tumour regions had resulted in lymphoproliferations suggested that each had independent clonal origins. Overall, these data suggest the presence of B cell clones with lymphoproliferative potential within primary NSCLC tumours that are under continuous immune surveillance. Since these cells can be expanded following transplantation into NSG mice, our data highlight the value of quality control measures to identify lymphoproliferations within xenograft pipelines and support the incorporation of strategies to minimise lymphoproliferations during the early stages of xenograft establishment pipelines. To present the histology data herein, we developed a Python-based tool for generating patient-level pathology overview figures from whole-slide image files; PATHOverview is available on GitHub (https://github.com/EpiCENTR-Lab/PATHOverview).

Recent research on Later Stone Age (LSA) San rock art in southern Africa has unveiled some of the paint recipes the artists employed. However, these discoveries still need to be linked to human activities in or near the rock shelters where the paintings were made. In this paper, we report characterization and dating results from the catchment of the Metolong Dam, Phuthiatsana Valley, Lesotho. A total of 92 rock painting samples, six grindstones with traces of colouring materials from an excavated context, and 17 potential raw colouring materials were studied. We identified three previously unreported ingredients used by the artists: manganese oxides, calcined bones, and soot. Grindstones are stained with the same raw materials that the painters used. We propose that one of them may have served to prepare the red pigment used to make a human figure and a bichrome eland at Ha Makotoko, but direct links remain difficult to establish with certainty. The potential colouring materials in the valley are red clays, white clays (kaolinite and illite-or-montmorillonite), and gypsum, three compounds used as paints by the artists. Tests conducted to verify their suitability for paintings show these materials may have been ground, but settling (after pre-grinding) offers a quicker and easier way to obtain a fine powder as observed in the paints. Finally, 12 AMS dates provide an initial framework for studying the changing use of paint recipes in the Phuthiatsana Valley over time. Charcoal appears to have been employed over a period of at least 3000 years and carbon black for at least 2000 years, with soot seemingly used only before 2000 cal. BP. This study is currently the largest characterization and dating study of LSA rock art in southern Africa and shows the potential that such combined investigations offer for linking excavated and parietal components of the region's hunter-gatherer archaeological record.

This paper reports on the steps taken to mitigate the impact of the Metolong Dam (Lesotho) on the rock art present within the catchment of its associated reservoir. Mitigation took four major forms: comprehensive survey and documentation, including both photography and tracing; pigment characterization and radiocarbon dating; exploration of the ongoing significance of rock art as a form of living heritage for people living in the vicinity; and removal of selected panels for permanent safekeeping. These steps are placed within the wider context of other cultural heritage management projects in Africa and their success evaluated. Recommendations are made for how similar work should be undertaken in future.

Background Rare diseases (RD) are a diverse collection of more than 7–10,000 different disorders, most of which affect a small number of people per disease. Because of their rarity and fragmentation of patients across thousands of different disorders, the medical needs of RD patients are not well recognized or quantified in healthcare systems (HCS). Methodology We performed a pilot IDeaS study, where we attempted to quantify the number of RD patients and the direct medical costs of 14 representative RD within 4 different HCS databases and performed a preliminary analysis of the diagnostic journey for selected RD patients. Results The overall findings were notable for: (1) RD patients are difficult to quantify in HCS using ICD coding search criteria, which likely results in under-counting and under-estimation of their true impact to HCS; (2) per patient direct medical costs of RD are high, estimated to be around three–fivefold higher than age-matched controls; and (3) preliminary evidence shows that diagnostic journeys are likely prolonged in many patients, and may result in progressive, irreversible, and costly complications of their disease Conclusions The results of this small pilot suggest that RD have high medical burdens to patients and HCS, and collectively represent a major impact to the public health. Machine-learning strategies applied to HCS databases and medical records using sentinel disease and patient characteristics may hold promise for faster and more accurate diagnosis for many RD patients and should be explored to help address the high unmet medical needs of RD patients.

BackgroundSymptomatic, partial-thickness rotator cuff tears (sPTRCT) are problematic. Management of sPTRCT with fresh, uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the point of care is safe and leads to improved shoulder function without adverse effects. This study tested the hypothesis that management of sPTRCT with injection of UA-ADRCs is safe and more effective than injection of corticosteroid even in the long run.MethodsSubjects who had completed a former randomized controlled trial were enrolled in the present study. At baseline these subjects had not responded to physical therapy treatments for at least six weeks, and were randomly assigned to receive either a single injection of an average 11.4 × 106 UA-ADRCs (n = 11) or a single injection of 80 mg of methylprednisolone (n = 5). Safety was assessed by rigorously documenting and evaluating treatment emergent adverse events. As per protocol efficacy was assessed using the ASES Total score, RAND Short Form-36 Health Survey (SF-36) Total score and VAS pain score at 24 weeks (W24) and W52 post-treatment as well as at 33.2 ± 1.0 (mean ± standard deviation) months (M33) and 40.6 ± 1.9 months (M41) post-treatment. Magnetic resonance imaging (MRI) of the index shoulder was performed at baseline, W24, W52, M33 and M41 post-treatment.ResultsThere were no greater risks connected with injection of UA-ADRCs than those connected with injection of corticosteroid. Injection of UA-ADRCs resulted in significantly higher mean ASES Total scores at W24, W52 and M41, a significantly higher mean SF-36 Total score at W24, and significantly higher mean VAS Pain scores at W24 and W52 post-treatment than injection of corticosteroid (pConclusionsThe present study further supports management of sPTRCT with injection of UA-ADRCs.Trial registrationClinicaltrials.govNCT04077190(September 4, 2019).

Mouse models of CLN3 Batten disease, a rare lysosomal storage disorder with no cure, have improved our understanding of CLN3 biology and therapeutics through their ease of use and a consistent display of cellular pathology. However, the translatability of murine models is limited by disparities in anatomy, body size, life span, and inconsistent, subtle behavior deficits that can be difficult to detect in CLN3 mutant mouse models, limiting their utility in preclinical studies. Here we present a longitudinal characterization of a novel miniswine model of CLN3 disease that recapitulates the most common human pathogenic variant, an exon 7-8 deletion (CLN3Δex7/8). Progressive pathology and neuron loss is observed in various regions of the CLN3Δex7/8 miniswine brain and retina. Additionally, mutant miniswine present with vision impairment and motor abnormalities, similar to deficits seen in human patients. Taken together, the CLN3Δex7/8 miniswine model shows consistent and progressive Batten disease pathology and behavioral impairment mirroring clinical presentation, demonstrating its value in studying the role of CLN3 and safety/efficacy of novel disease modifying therapeutics.