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Recovering the agency, skill and innovation of archaeological field assistants from historical encounters is essential to interrogating processes of knowledge production, but is often hampered by access to appropriate archival sources and methods. We detail a field project from early twentieth-century Basutoland (modern-day Lesotho) that is unique both for its aim to salvage details of rock-art production as a dying craft and for its archive chronicling the project's intellectual journey from experiment to draft manuscripts to published work over more than three decades. We argue that critical historiographic attention to this archive offers a guide for examining the intimate dynamics of fieldwork and the effects of these micropolitics on the archaeological canon. We demonstrate how sustained attention to long processes of knowledge production can pinpoint multiple instances in which the usability of field assistants’ scientific knowledge is qualified, validated, or rejected, and in this case how an African assistant is transformed into an ethnographic interlocutor. For rock-art studies especially, this represents a need for interrogating the epistemic cultures—not just the content—of foundational historical data.

This chapter describes the rock art of nineteenth-century Nomansland in the Maloti-Drakensberg region of South Africa. It explores a material and symbolic response to the arrival of European colonialists, particularly their practices of dress and animal husbandry that were frequently the setting for intercultural contact. The authors identify a specific form of rock art as an important ‘coping mechanism’, an attempt to manipulate, reorder, and control particular areas of social articulation. Important points of social continuity are ensured by enmeshing fine-line images that give reference to the ‘old’ ways of livestock raiding, with other stylistic depictions of the ‘new’, thereby serving to align multiple worldviews and language cultures into mutual understanding and collective identity.

CLN2 Batten disease is a lysosomal disorder in which pathogenic variants in CLN2 lead to reduced activity in the enzyme tripeptidyl peptidase 1. The disease typically manifests around 2 to 4 years of age with developmental delay, ataxia, seizures, inability to speak and walk, and fatality between 6 and 12 years of age. Multiple Cln2 mouse models exist to better understand the etiology of the disease; however, these models are unable to adequately recapitulate the disease due to differences in anatomy and physiology, limiting their utility for therapeutic testing. Here, we describe a new CLN2

We recently demonstrated that HCl-acidified drinking water, which is widely used in laboratory animal facilities, had some beneficial effects in the Cln3−/− mouse model of juvenile Batten disease, a neurodegenerative lysosomal storage disorder1. Here we tested if acidified drinking water has therapeutic effects in Cln1R151X nonsense mutant mice, a model of the infantile form of Batten disease. In Cln1R151X mice, acidified drinking water received from weaning prevented the impairment in pole climbing ability measured at 3 and 6 months of age. Histopathological analysis of the brain at 6 months showed that acidified drinking water decreased the amount of lysosomal storage material, reduced astrocytosis in the striatum and somatosensory barrelfield cortex, and attenuated microglial activation in the thalamus. Compared to wild-type mice, the gut microbiota of Cln1R151X mice was markedly different. Acidified drinking water significantly altered the gut microbiota composition of Cln1R151X mice, indicating a contribution of gut bacteria to the therapeutic effects of acidified water. Our results in Cln1R151X mice suggest that acidified drinking water may have beneficial effects for patients with infantile Batten disease. This study also verifies that acidified drinking water can modify disease phenotypes in mouse models, contributing to the inter-laboratory variations in neurological and pathological findings.

Arctic soils are constantly subjected to microbial invasion from either airborne, marine, or animal sources, which may impact local microbial communities and ecosystem functioning. However, in winter, Arctic soils are isolated from outside sources other than snow, which is the sole source of microorganisms. Successful colonisation of soil by snow microorganisms depends on the ability to survive and compete of both, the invading and resident community. Using shallow shotgun metagenome sequencing and amplicon sequencing, this study monitored snow and soil microbial communities throughout snow melt to investigate the colonisation process of Arctic soils. Microbial colonisation likely occurred as all the characteristics of successful colonisation were observed. The colonising microorganisms originating from the snow were already adapted to the local environmental conditions and were subsequently subjected to many similar conditions in the Arctic soil. Furthermore, competition-related genes (e.g. motility and virulence) increased in snow samples as the snow melted. Overall, one hundred potentially successful colonisers were identified in the soil and, thus, demonstrated the deposition and growth of snow microorganisms in soils during melt.

Recent work on a well-known San rock art panel from South Africa shows that continued movement between, on the one hand, San beliefs and rituals and, on the other, the images themselves allows us t...

24 pages, 2 figures, 1 table, supporting Information https://doi.org/10.1111/brv.12679, Important findings from the second decade of the 21st century on the impact of environmental change on biological processes in the Antarctic were synthesised by 26 international experts. Ten key messages emerged that have stakeholder¿relevance and/or a high impact for the scientific community. They address (i) altered biogeochemical cycles, (ii) ocean acidification, (iii) climate change hotspots, (iv) unexpected dynamism in seabed¿dwelling populations, (v) spatial range shifts, (vi) adaptation and thermal resilience, (vii) sea ice related biological fluctuations, (viii) pollution, (ix) endangered terrestrial endemism and (x) the discovery of unknown habitats. Most Antarctic biotas are exposed to multiple stresses and considered vulnerable to environmental change due to narrow tolerance ranges, rapid change, projected circumpolar impacts, low potential for timely genetic adaptation, and migration barriers. Important ecosystem functions, such as primary production and energy transfer between trophic levels, have already changed, and biodiversity patterns have shifted. A confidence assessment of the degree of `scientific understanding¿ revealed an intermediate level for most of the more detailed sub¿messages, indicating that process¿oriented research has been successful in the past decade. Additional efforts are necessary, however, to achieve the level of robustness in scientific knowledge that is required to inform protection measures of the unique Antarctic terrestrial and marine ecosystems, and their contributions to global biodiversity and ecosystem services, With the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)

(1) Background: Conclusions of meta-analyses of clinical studies may substantially influence opinions of prospective patients and stakeholders in healthcare. Nineteen meta-analyses of clinical studies on the management of primary knee osteoarthritis (pkOA) with stem cells, published between January 2020 and July 2021, came to inconsistent conclusions regarding the efficacy of this treatment modality. It is possible that a separate meta-analysis based on an independent, systematic assessment of clinical studies on the management of pkOA with stem cells may reach a different conclusion. (2) Methods: PubMed, Web of Science, and the Cochrane Library were systematically searched for clinical studies and meta-analyses of clinical studies on the management of pkOA with stem cells. All clinical studies and meta-analyses identified were evaluated in detail, as were all sub-analyses included in the meta-analyses. (3) Results: The inconsistent conclusions regarding the efficacy of treating pkOA with stem cells in the 19 assessed meta-analyses were most probably based on substantial differences in literature search strategies among different authors, misconceptions about meta-analyses themselves, and misconceptions about the comparability of different types of stem cells with regard to their safety and regenerative potential. An independent, systematic review of the literature yielded a total of 183 studies, of which 33 were randomized clinical trials, including a total of 6860 patients with pkOA. However, it was not possible to perform a scientifically sound meta-analysis. (4) Conclusions: Clinicians should interpret the results of the 19 assessed meta-analyses of clinical studies on the management of pkOA with stem cells with caution and should be cautious of the conclusions drawn therein. Clinicians and researchers should strive to participate in FDA and/or EMA reviewed and approved clinical trials to provide clinically and statistically valid efficacy.

SummaryThe airway epithelium is a key protective barrier, the integrity of which is preserved by the self-renewal and differentiation of basal stem cells. Epithelial cells are central to the pathogenesis of multiple lung diseases. In chronic lung diseases, increasing age is a principle risk factor. Few studies have explored the differences between airway epithelial cells in children and adults and how the function of basal stem cells changes during ageing is poorly understood. Here, we analyze airway epithelial cells from children and adults in homeostatic conditions (laser capture-microdissected whole epithelium and fluorescence-activated cell-sorted basal cells) and in proliferation-inducing cell culture conditions. We find that, while the cellular composition of the pediatric and adult tracheobronchial epithelium is broadly similar, in cell culture, pediatric airway epithelial cells displayed higher colony-forming ability, sustained in vitro growth and outcompeted adult cells in competitive proliferation assays. In RNA sequencing experiments, we observed potentially important differences between epithelium from children and adults, including higher baseline interferon-associated gene expression in pediatric epithelium. Our results demonstrate cell-intrinsic differences in transcriptional profile and regenerative capacity between proximal airway epithelial cells of children and adults.Graphical abstract

Accumulated evidence indicates that the gut microbiota affects brain function and may be altered in neurological diseases. In this study, we analyzed the gut microbiota in Cln1R151X and Cln2R207X mice, models of the childhood neurodegenerative disorders, infantile CLN1 and late infantile CLN2 Batten diseases. Significant alterations were found in the overall gut microbiota composition and also at the individual taxonomic ranks as compared to wild-type mice. The disease-specific alterations in the gut microbiota of Cln1R151X and Cln2R207X mice may contribute to the disease phenotypes observed in these mouse models. We also compared the gut microbiota composition of three wild-type mouse strains frequently used in transgenic studies: 129S6/SvEv, C57BL/6J and mixed 129S6/SvEv × C57BL/6J. Our results show that the gut microbiota of 129S6/SvEv and C57BL/6J mice differs remarkably, which likely contributes to the known, pronounced differences in behavior and disease susceptibility between these two wild-type mouse strains.

CLN3 Batten disease (CLN3 disease) is a pediatric lysosomal storage disorder that presents with progressive blindness, motor and cognitive decline, seizures, and premature death. CLN3 disease results from mutations in CLN3 with the most prevalent mutation, a 966 bp deletion spanning exons 7–8, affecting ~ 75% of patients. Mouse models with complete Cln3 deletion or Cln3Δex7/8 mutation have been invaluable for learning about both the basic biology of CLN3 and the underlying pathological changes associated with CLN3 disease. These models, however, vary in their disease presentation and are limited in their utility for studying the role of nonsense mediated decay, and as a consequence, in testing nonsense suppression therapies and read-through compounds. In order to develop a model containing a disease-causing nonsense point mutation, here we describe a first-of-its-kind Cln3Q352X mouse model containing a c.1054C > T (p.Gln352Ter) point mutation. Similar to previously characterized Cln3 mutant mouse lines, this novel model shows pathological deficits throughout the CNS including accumulation of lysosomal storage material and glial activation, and has limited perturbation in behavioral measures. Thus, at the molecular and cellular level, this mouse line provides a valuable tool for testing nonsense suppression therapies or read through compounds in CLN3 disease in the future.

Background: Polygenic risk scores (PRS) integrate risk information from breast cancer associated SNPs (single nucleotide polymorphism). The risk scores have mostly been developed in populations of European ancestry, and have been shown to improve risk prediction over standard breast cancer risk models in these populations. The ability of the PRS to personalize screening is currently being studied. We included PRS as a component of breast cancer risk assessment in the WISDOM Study, a trial of personalized vs. annual breast cancer screening. In order to account for race/ethnicity in PRS risk assessment, we developed a race/ethnicity calibrated and inclusive PRS risk score that we incorporated here into the Gail model to determine impact on risk stratification. Methods: We constructed two different PRS for each race/ethnicity: For Caucasian populations, we constructed two PRS based on SNPs discovered in European-ancestry populations. One PRS was based on 167 SNPs (PRS-167) and the other based on 313 SNPs (PRS-313) from the Breast Cancer Association Consortium studies as previously published. For each of the Asian-, Hispanic- and African-ancestry populations we added additional ancestry specific SNPs to the PRS-167 or the PRS-313, that were literature curated or our own identified race/ethnicity SNPs that we validated to provide independent risk prediction for their ancestry group: Asian added 10 or 4 additional SNPs, Hispanic 2 SNPs, and African 8 and 12 SNPs, respectively to each model. We tested this approach using datasets from several case-control studies of multiple racial/ethnic populations and compared discrimination of the models using area under the receiver operating characteristic curve (AUROC). Furthermore, we applied our multi-racial/ethnic PRS-313 in a sample of ~3000 multi-racial/ethnic women from the Athena Breast Screening Registry, case-control sampled by Gail score to be at elevated (Gail >1.67) or average (Gail≤1.67) risk, to evaluate the impact of our multi-ethnic adjustment on risk stratification. Results: A multi-race/ethnicity adjusted PRS-313 and PRS-167 plus ethnicity specific SNPs has moderate-high discriminatory power with AUROCs of 0.65 and 0.64, respectively. The specificity of our PRS-167 in the different race/ethnicity ancestries performs relatively well in Asian (AUROC 0.59) and Hispanic (AUROC 0.63) populations, but less so in African-ancestry (AUROC 0.56). Incorporating multi-race/ethnicity PRS into Gail model selected women, resulted in 20% of average-risk women transitioning to risk above 1.67%, and conversely, 38% of elevated risk patients were reclassified to average risk. Conclusion: We constructed a PRS risk score that can be applied to multi-ethnic populations and found moderate-high discrimination. Additional work is needed for the African-ancestry population. The addition of a multi-race/ethnicity SNP model to risk classification based on the Gail model significantly changes risk stratification and clinical care recommendations due to down- or up-reclassification of women at average versus elevated risk. Citation Format: Sarah Theiner, Donglei Hu, Scott Huntsman, Yiwey Shieh, Laura Fejerman, Irene Acerbi, Sarah D Sawyer, Paige Kendall, Wei Zheng, Dezheng Huo, Olufunmilayo I Olopade, Christopher Haiman, Karla Kerlikowske, Steven Cummings, Ester John, Gabriela Torres-Mejia, Lawrence H Kushi, Denise Wolf, Jeffery A Tice, David A Pearce, Laura Esserman, Athena Breast Health Network Investigators and Advocate Partners, Laura J van ‘t Veer, Elad Ziv. A breast cancer multi-racial/ethnic polygenic risk score for improved personalized breast cancer screening [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-05.

Since the late 1990s, executives have been warned that explosive company growth is essential to producing superior financial performance. For executives who recognize that this contention accurately describes their situation and want to upgrade their competitive capabilities, the challenge is planning to grow fast while understanding and avoiding the risk of fast failure. In this article, we identify promising competitive strategies by studying businesses that have sought high-growth and succeeded in achieving it. The dataset consists of the fastest growing new ventures in the U.S. as selected for the Inc. 500. The results of a quantitative and qualitative analysis show that these businesses rely on different combinations of attributes related to advanced technology, market aggressiveness, and functional excellence. We discuss 12 of these attributes and look at the demographic characteristics of the Inc. 500 and their implications for new venture creation.

PURPOSE OF REVIEW: The novel corona virus (SARS-CoV2) has been demonstrated to cause acute kidney injury due to direct cellular toxicity as well as due to a variety of autoimmune glomerular diseases. The concept of a surge of infected patients resulting in an overwhelming number of critical patients has been a central concern in healthcare planning during the COVID-19 era. RECENT FINDINGS: One crucial question remains as to how to manage patients with end stage renal disease and acute kidney injury in case of a massive surge of critically ill infected patients. Some publications address practical and ingenious solutions for just such a surge of need for renal replacement therapy. We present a plan for using a blood pump, readily available dialysis filter, and a prefilter and postfilter replacement fluid set up. This is in conjunction with multiple intravenous pumps to develop a simple hemofiltration apparatus. SUMMARY: The current set up may be a readily available option for use in critical situations where the need for renal replacement therapy outstrips the capacity of traditional hemodialysis services in a hospital or region.

Rare disease patients face many challenges including diagnostic delay, misdiagnosis and lack of therapies. However, early access to diagnosis and therapies can modify the management and the progression of diseases, which in return positively impacts patients, families and health care systems. The International Rare Diseases Research Consortium set up the multi-stakeholder Working Group on developing methodologies to assess the impact of diagnoses and therapies on rare disease patients. Using the patients' journey on the diagnostic paradigm, the Working Group characterized a set of metrics, tools and needs required for appropriate data collection and establishment of a framework of methodologies to analyze the socio-economic burden of rare diseases on patients, families and health care systems. These recommendations are intended to facilitate the development of methodologies and to better assess the societal impact of rare diseases.

Our indoor microbiome consists of a wide range of microbial taxa. Whilst many of these microbes are benign, some are beneficial, some harmful, yet our knowledge of the spatial heterogeneity of bacterial assemblages in our residential environment remains limited. To investigate the existence of a common core house dust bacterial microbiome we selected household vacuum dusts, collected through a citizen science approach, from homes across two bioclimatic regions (UK, Oceanic/Maritime and Greece, Mediterranean). Following the extraction of DNA from each dust sample, we targeted the bacterial 16S rRNA gene using Illumina NextSeq sequencing. PERMANOVA analysis of the microbial communities at family level grouped samples within their distinct bioclimatic region and SIMPER analysis at genus level identified the statistically significant taxa responsible for driving diversity between these groups. A “common to all” core house dust microbiome consisted of Acinetobacter, Massalia, Rubellimicrobium, Sphingomonas and Staphylococcus; genera typically associated with human occupancy and common environmental sources. Additionally, a “unique location specific” microbiome was identified, reflective of the bioclimatic region. The Greek dusts indicated a lower average diversity than the UK house dusts, with a high abundance of Rhizobiaceae in the Greek samples. Our study highlights citizen science as a powerful approach to access the indoor residential environment, at scale, and establishes the existence of a “core” house dust microbiome independent of bioclimatic region., JE acknowledges funding from the Natural Environment Research Council (Research Grant NE/T004401/1). MB and MC acknowledge research funding from Research England’s Expanding Excellence in England (E3) Fund as part of the Hub for Biotechnology in the Built Environment. KJ acknowledges funding for her PhD research programme from Northumbria University. Open access publication fees were provide by Northumbria University.

Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject’s individual age, sex, body mass index and ethnicity. UA-ADRCs were isolated from lipoaspirate from n = 232 subjects undergoing elective lipoplasty using the Transpose RT system (InGeneron, Inc.; Houston, TX, USA). The UA-ADRCs were assessed for the number of nucleated cells, cell viability and the number of viable nucleated cells per gram of adipose tissue harvested. Cells from n = 37 subjects were further characterized using four-channel flow cytometry. The present study shows, for the first time, that key characteristics of UA-ADRCs can be independent of the subject’s age, sex, BMI and ethnicity. This result has important implications for the general applicability of UA-ADRCs in regeneration of musculoskeletal tissue. Future studies must determine whether the independence of key characteristics of UA-ADRCs of the subject’s individual age, sex, BMI and ethnicity only applies to the system used in the present study, or also to others of the more than 25 different experimental methods and commercially available systems used to isolate UA-ADRCs from lipoaspirate that have been described in the literature.

We describe seasonal changes in the biogeochemistry, microbial community and ecosystem production of two glacial snowpacks in the maritime Antarctic during a cold summer. Frequent snowfall and low, intermittent melt on the glaciers suppressed surface photosynthesis and promoted net heterotrophy. Concentrations of autotrophic cells (algae and cyanobacteria) were therefore low (average: 150 - 500 cells mL-1), and short-term estimates of primary production were almost negligible in early summer (< 0.1 µg C L-1 d-1). However, order of magnitude increases in Chlorophyll a concentrations occurred later, especially within the mid-snowpack and ice layers below. Short-term primary production increased to ca. 1 µg C L-1 d-1 in mid-summer, and reached 53.1 µg C L-1 d-1 in a mid-snow layer close to an active penguin colony. However, there were significantly more bacteria than autotrophs in the snow (typically 103 cells mL-1, but > 104 cells mL-1 in basal ice near the penguin colony). The ratio of bacteria to autotrophs also increased throughout the summer, and short-term bacterial production rates (0.2 – 2000 µg C L-1 d-1) usually exceeded primary production, especially in basal ice (10 – 1400 µg C L-1 d-1). The basal ice represented the least diverse but most productive habitat, and a striking feature was its low pH (down to 3.3). Furthermore, all of the overlying snow cover became increasingly acidic as the summer season progressed, which is attributed to enhanced emissions from wet guano in the penguin colony. The study demonstrates that active microbial communities can be expected, even when snowmelt is intermittent in the Antarctic summer.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B-cells that accumulate in the lung adjacent to areas of active fibrosis. We have shown previously a requirement for B-cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B-cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B-cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20 B-cell ablation did not reduce fibrosis in this model; however, immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20-treated mice retained a high frequency of CD19+CD138+plasma cells. Interestingly, high levels of CD138+cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes plasma cells, reduced the level of Blm-induced lung fibrosis, implicating plasma cells as important effector cells in the development and progression of pulmonary fibrosis.