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A 67 year-old female presented to our centre with a 2 day history of right flank pain, clinically suggestive of ureteric colic. Computed tomography (CT) confirmed a 6mm right ureteric calculus. However, CT also revealed a large 13cm ipsilateral renal mass, concerning for renal cell carcinoma (RCC). At ureteroscopy for management of the obstructing calculus, a small papillary lesion was noted in the bladder, and excised. Histology confirmed pTa low-grade transitional cell carcinoma. Following discussion at the Urology multidisciplinary tumour board, MRI venogram (MRV) was recommended to delineate the extension of tumour into the renal vein, and to characterise a pelvic mass seen on original CT. MRV showed enhancing material extending into the IVC, consistent with tumour thrombus. However, it also identified a concerning 6cm solid ovarian mass. The patient proceeded to open right radical nephrectomy and IVC thrombectomy, hysterectomy, bilateral salpingo-oopherectomy, and omental biopsy, with combined input from Urological, Gynaecological and Vascular surgical teams. Post-operative course was uneventful. Histology showed an 11cm pT3a G2 clear cell RCC, and 7.5cm ovarian fibroma, both fully excised. This case demonstrated the serendipity of a simple ureteric calculus precipitating a cascade of investigations, that ultimately led to complete resection of three primary neoplasms.

Stable carbon isotope analysis is increasingly used in archaeology as an indicator of crop water status and/or water management regime. While the technique shows promise, robust modern baseline studies are required to inform and validate archaeological interpretations. Here, we test stable carbon isotope values as a crop water status proxy in a monsoonal climatic context for the first time. Specifically, we test the relationship between grain stable carbon isotope values (δ13Cgrain), water availability, irrigation and soil type in barley ( Hordeum vulgare L. (Zohary and Hopf.)) in north-west India, with the aim of deriving a locally-appropriate model for isotopic interpretation. We test this relationship across a substantial rainfall gradient (200–1000 mm/year) and find a negative logarithmic relationship between climatic water availability and δ13C. However, there is significant noise in the relationship, and we report δ13Cgrain variation of over 3‰ amongst samples drawn from similar climatic contexts. Soil type, irrigation type and irrigation frequency have no clear modifying effects. We conclude that: (1) barley stable carbon isotope values can act as an archaeological water status proxy in monsoonal areas, but will be most sensitive in areas receiving

We screened 29 strains of Neisseria gonorrhoeae and found 16/21 strains that resisted killing by normal human serum and 0/8 serum sensitive strains that bound the complement regulator, C4b-binding protein (C4bp). Microbial surface-bound C4bp demonstrated cofactor activity. We constructed gonococcal strains with hybrid porin (Por) molecules derived from each of the major serogroups (Por1A and Por1B) of N. gonorrhoeae, and showed that the loop 1 of Por1A is required for C4bp binding. Por1B loops 5 and 7 of serum-resistant gonococci together formed a negatively charged C4bp-binding domain. C4bp-Por1B interactions were ionic in nature (inhibited by high salt or by heparin), whereas the C4bp-Por1A bond was hydrophobic. Only recombinant C4bp mutant molecules containing the NH2-terminal α-chain short consensus repeat (SCR1) bound to both Por1A and Por1B gonococci, suggesting that SCR1 contained Por binding sites. C4bp α-chain monomers did not bind gonococci, indicating that the polymeric form of C4bp was required for binding. Using fAb fragments against C4bp SCR1, C4bp binding to Por1A and Por1B strains was inhibited in a complement-dependent serum bactericidal assay. This resulted in complete killing of these otherwise fully serum resistant strains in only 10% normal serum, underscoring the importance of C4bp in mediating gonococcal serum resistance.

Screening of 29 strains of Neisseria gonorrhoeae revealed that 16/21 serum resistant strains and 0/8 serum sensitive strains bound C4bp, suggesting that C4bp binding to gonococci could contribute to serum resistance. C4bp bound to gonococci retained cofactor (C4b-degrading) function. Using allelic exchange to construct strains with hybrid Por1A/B molecules, we demonstrate that the N-terminal loop (loop 1) of Por1A is required for C4bp binding. Serum resistant Por1B gonococcal strains also bind C4bp via their Por molecule. Using allelic exchange and site-directed mutagenesis, we have shown that loops 5 and 7 together form a negatively charged C4bp binding domain. C4bp-Por1B interactions are ionic in nature (inhibited by high salt as well as by heparin), while the C4bp-Por1A bond is hydrophobic. mAbs directed against SCR1 of the α-chain of C4bp inhibit C4bp binding to both Por1A and Por1B. Furthermore, only recombinant C4bp mutant molecules that contain α-chain SCR1 bind both Por1A and Por1B gonococci, confirming that SCR1 contains Por binding sites. C4bp α-chain monomers do not bind strains with either Por molecule, suggesting that the polymeric form of C4bp is required for binding to gonococci. Inhibition of C4bp binding to serum resistant Por1A and Por1B strains in a serum bactericidal assay using fAb fragments against C4bp SCR1 results in complete killing at 30 min of otherwise fully serum resistant strains in only 10% normal serum, underscoring the role of C4bp in mediating gonococcal serum resistance. © 2001 Elsevier Science B.V.

This paper presents novel insights into the archaeology of food in ancient South Asia by using lipid residue analysis to investigate what kinds of foodstuffs were used in ceramic vessels by populations of the Indus Civilisation in northwest India. It examines how vessels were used in urban and rural Indus settlements during the Mature Harappan period (c.2600/2500–1900 BC), the relationship between vessels and the products within them, and identifies whether changes in vessel use occurred from the Mature Harappan to Late Harappan periods, particularly during climatic instability after 4.2 ka BP (c.2100 BC). Despite low lipid concentrations, which highlight challenges with conducting residue analysis in arid, seasonally-wet and alkaline environments, 71% of the vessels yielded appreciable quantities of lipid. Lipid profiles revealed the use of animal fats in vessels, and contradictory to faunal evidence, a dominance of non-ruminant fats, with limited evidence of dairy processing. The absence of local modern reference fats makes this dataset challenging to interpret, and it is possible that plant products or mixtures of plant and animal products have led to ambiguous fatty acid-specific isotopic values. At the same time, it appears that urban and rural populations processed similar types of products in vessels, with limited evidence for change in vessel use from the urban to the post-urban period. This study is a systematic investigation into pot lipid residues from multiple sites, demonstrating the potential of the method for examining ancient Indus foodways and the need for the development of further research in ancient organic residues in South Asia., Highlights • Systematic study on ceramic lipid residues from rural and urban sites of the Indus Civilisation in northwest India. • Lipid residue analysis provides chemical evidence for milk, meat, and possible mixtures of products and/or plant consumption. • Similarities in vessel use across settlements suggest common regional culinary practices. • Evidence for continuity in vessel usage practices after the decline of urbanism.

Background: Despite a higher prevalence of traumatic spinal cord injury (TSCI) amongst Canadian Indigenous peoples, there is a paucity of studies focused on Indigenous TSCI. We present the first Canada-wide study comparing TSCI amongst Canadian Indigenous and non-Indigenous peoples. Methods: This study is a retrospective analysis of prospectively-collected TSCI data from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) from 2004-2019. We divided participants into Indigenous and non-Indigenous cohorts and compared them with respect to demographics, injury mechanism, level, severity, and outcomes. Results: Compared with non-Indigenous patients, Indigenous patients were younger, more female, less likely to have higher education, and less likely to be employed. The mechanism of injury was more likely due to assault or transportation-related trauma in the Indigenous group. The length of stay for Indigenous patients was longer. Indigenous patients were more likely to be discharged to a rural setting, less likely to be discharged home, and more likely to be unemployed following injury. Conclusions: Our results suggest that more resources need to be dedicated for transitioning Indigenous patients sustaining a TSCI to community living and for supporting these patients in their home communities. A focus on resources and infrastructure for Indigenous patients by engagement with Indigenous communities is needed.

In their paper published in Clinical Nutrition, Ellegård and colleagues report that they can distinguish between individuals on different habitual diets (vegan, vegetarian, omnivore) based on the carbon and nitrogen isotopic ratios of their hair (1). The finding is not new, and has been previously reported in the literature over the last 22 years (2-4). The authors do not properly acknowledge that previous work has shown similar or identical findings framed around the same hypothesis, despite such work being described and discussed in multiple works that they do cite (5-7). I would argue that such findings now come under the heading of common knowledge in many fields, even to the extent of being used as a student practical exercise in many university degrees across the world including in my own teaching – I have a database of hundreds of hair samples with associated dietary records.

During the sixteenth to eighteenth centuries, Spanish ships sailed around the globe connecting Spain to its colonies. While documentary records offer rich details concerning life on board ship, archaeological information is essential to generating a full picture of the past. The cemetery at Old St Bernard’s Hospital, Gibraltar, provides an opportunity to study the skeletal remains of sailors. Following previous osteological research, carbon, nitrogen, oxygen and strontium isotope analyses were undertaken on thirty-three of these individuals. The results show that the, largely male, individuals had various different diets during life and came from several different places. Diets were largely based on C3food chains; some individuals consumed C3foods with low δ13C values; others consumed some marine foods, and a few individuals had a high trophic level diet, through the consumption of either freshwater resources or a high proportion of animal protein. The individuals spent their childhoods in several different places, although these homelands do not correlate simply with dietary variation. This variety in diets and homelands is consistent with our expectations for this hospital site given its location in a post-mediaeval entrepôt. The interpretation of these results are greatly helped by the available historical information and this has broader implications for the interpretation of isotope data elsewhere where the historical context of the site and the mobility patterns of the individuals are less well known.

Objective To assess whether instillation of lidocaine gel both before and after flexible cystoscopy is more effective at reducing post procedural symptoms than instillation of lidocaine gel pre flexible cystoscopy alone. We hypothesise that inadequate urethral dwell time and dilution of lidocaine gel by the irrigation fluid during flexible cystoscopy limits its anaesthetic efficacy. Only one other study has attempted to reduce bothersome urinary symptoms through an intervention after flexible cystoscopy. Methods This was a randomised controlled trial in which patients were randomised 1:1 to receive lidocaine gel pre and post flexible cystoscopy (treatment) or lidocaine gel pre flexible cystoscopy only (control). Patient-reported outcome measures were used to assess symptoms and quality of life prior to cystoscopy, on day 2 and day 7 post cystoscopy. Result Fifty patients were divided equally between the treatment and control groups. There were no significant differences in baseline characteristics between the groups (p = 1.000). An overall symptoms variable was measured, though no significant difference was found in the distribution of responses between the groups at baseline, 2 or 7 days after the flexible cystoscopy (p = 0.423, 0.651,0.735). In the treatment group, 1 patient (4.0%) presented to a doctor for review following flexible cystoscopy, and 4 patients (16.0%) presented in the control group (p = 0.349). Conclusion Initial study results suggest that post-operative lidocaine does not significantly limit the exacerbation of urinary symptoms following flexible cystoscopy; however, our results are not powered to detect a small difference. We do not recommend a change in practice based on our results.

Sea turtles complete migrations across vast distances, covering entire ocean basins. To track these migrations, satellite tracking tags are attached to their shells. The impact of these tags must be considered to ensure that turtles' natural behavior is not artificially and adversely impacted through tag-related drag, and that the data collected by a small sample of sea turtles accurately represents the larger population. Additionally, it can be difficult to study animal energetics in the field over large migration distances. In this work, we modify a computational behavior model to study how satellite tracking tags affect turtle migration behavior. Our agent based model contains synthetic magnetic field environments that are used for navigation cues, an ocean current, resource distributions that represent locations of food, and an agent that attempts to migrate to several different goals. The agent loses energy as it progresses, and searches for the resource distributions to replenish itself. Our novel simulation framework demonstrates the relationship between an agent's available energy capacity, its energy consumption based on mechanical power expended, and its ability to navigate to all migratory goal points. This study can be utilized to (1) probe the impacts of an animal's energy capacity and foraging behavior on its resulting navigation and ecology, (2) guide future satellite tag designs, and (3) develop usage recommendations for a suitable tracking tag based on the type of experiment being conducted. Our model can be expanded beyond sea turtles to study other marine species (e.g., sharks, whales). Additionally, this model could be expanded to other domains within the marine environment. For example, it could be modified to examine design trade-offs in remotely operated vehicles (ROVs), which share many of the same operational constraints as sea turtles and other migratory species.

The identification of precision blood biomarkers which can accurately indicate damage to brain tissue could yield molecular diagnostics with the potential to improve how we detect and treat neurological pathologies. However, a majority of candidate blood biomarkers for neurological damage that are studied today are proteins which were arbitrarily proposed several decades before the advent of high-throughput omic techniques, and it is unclear whether they represent the best possible targets relative to the remainder of the human proteome. Here, we leveraged mRNA expression data generated from nearly 12,000 human specimens to algorithmically evaluate over 17,000 protein-coding genes in terms of their potential to produce blood biomarkers for neurological damage based on their expression profiles both across the body and within the brain. The circulating levels of proteins associated with the top-ranked genes were then measured in blood sampled from a diverse cohort of patients diagnosed with a variety of acute and chronic neurological disorders, including ischemic stroke, hemorrhagic stroke, traumatic brain injury, Alzheimer's disease, and multiple sclerosis, and evaluated for their diagnostic performance. Our analysis identifies several previously unexplored candidate blood biomarkers of neurological damage with possible clinical utility, many of which whose presence in blood is likely linked to specific cell-level pathologic processes. Furthermore, our findings also suggest that many frequently cited previously proposed blood biomarkers exhibit expression profiles which could limit their diagnostic efficacy.

Traumatic dental injuries (TDIs) occur most frequently in children and young adults. Older adults also suffer TDIs but at significantly lower rates than individuals in the younger cohorts. Luxation injuries are the most common TDIs in the primary dentition, whereas crown fractures are more commonly reported for the permanent teeth. Proper diagnosis, treatment planning and follow up are very important to assure a favorable outcome. These updates of the International Association of Dental Traumatology's (IADT) Guidelines include a comprehensive review of the current dental literature using EMBASE, MEDLINE, PUBMED, Scopus, and Cochrane Databases for Systematic Reviews searches from 1996 to 2019 and a search of the journal Dental Traumatology from 2000 to 2019. The goal of these guidelines is to provide information for the immediate or urgent care of TDIs. It is understood that some follow-up treatment may require secondary and tertiary interventions involving dental and medical specialists with experience in dental trauma. As with previous guidelines, the current working group included experienced investigators and clinicians from various dental specialties and general practice. The current revision represents the best evidence based on the available literature and expert opinions. In cases where the published data were not conclusive, recommendations were based on the consensus opinions of the working group. They were then reviewed and approved by the members of the IADT Board of Directors. It is understood that guidelines are to be applied using careful evaluation of the specific clinical circumstances, the clinician's judgment, and the patient's characteristics, including the probability of compliance, finances and a clear understanding of the immediate and long-term outcomes of the various treatment options vs non-treatment. The IADT does not, and cannot, guarantee favorable outcomes from adherence to the Guidelines. However, the IADT believes that their application can maximize the probability of favorable outcomes.

BACKGROUND This study aims to evaluate allograft and patient outcomes among recipients of kidney transplants after non-renal solid organ transplants. We also aim to compare our findings with recipients of a repeat kidney transplant. METHODS We performed an analysis on kidney transplant recipients who underwent kidney transplantation after a non-renal solid organ transplant. Survival data were stratified into 2 groups: Group A (n = 37) consisted of recipients of a kidney transplant after prior non-renal solid organ transplant, and Group B (n = 330) consisted of recipients of a repeat kidney transplant. RESULTS The 1-,5-, and 10-year graft survival (death-censored) for recipients of a kidney transplant post-non-renal solid organ transplant (Group A) were 97.3%, 91.5%, and 86.9%, compared with 97.9%, 90.2%, and 83.4% for recipients of a repeat kidney transplant (Group B) (p = .32). The 1-, 5-, and 10-year patient survival rates were 97.3%, 82.7%, and 79.1% in Group A compared to 97.9%, 90.2%, and 83.4% in Group B. Unadjusted overall patient survival was significantly lower for Group A (p = .017). CONCLUSION Kidney transplant recipients who have undergone a previous non-renal solid organ transplant have similar allograft survival outcomes, but higher long-term mortality rates compared to repeat kidney transplant recipients.

BACKGROUND/AIMS Management of traumatic dental injuries (TDI) can be expensive and time-consuming, yet very few studies have addressed the cost of their management. The aim of this study was to evaluate the total cost and the number of visits required to treat dental injuries to permanent incisors in children and adolescents over a 1-year period. MATERIALS AND METHODS Ninety-five children with at least one traumatic dental injury to their permanent incisors were enrolled and managed according to the International Association of Dental Traumatology guidelines. Injuries were grouped into complex (n = 74) and non-complex injuries (n = 21) and divided by the date of injury. Total cost was the sum of the direct (capital, staff, materials and laboratory fees) and indirect costs (travel, childcare and missed working hours). All data were collected prospectively through hospital records and questionnaires at each visit over one year. Data were analysed using a linear regression model for the cost and the number of visits. Logistic regression was used to analyse differences between complex and non-complex injuries (α = 5%). RESULTS The mean total cost for complex and non-complex injuries was €1687.9 and €1350.8, respectively. The treatment of non-complex injuries was cheaper than for complex injuries (P = .047). The cost of follow-up visits 4 years after the injury was significantly lower when compared to the treatment during the first year (P = .002). Travelling longer distances (>50 km) for treatment increased the overall cost of the treatment. There was no difference in the number of visits required for complex (mean = 5.6) and non-complex (mean = 4.9) injuries, but there were significantly fewer visits required in year 4 onwards (P

RNP granules are membrane-less compartments within cells, formed by phase separation, that function as regulatory hubs for diverse biological processes. However, the mechanisms by which RNAs and proteins interact to promote RNP granule structure and functionin vivoremain unclear. InXenopus laevisoocytes, maternal mRNAs are transported as large RNPs to the vegetal hemisphere of the developing oocyte, where local translation is critical for proper embryonic patterning. Here, we demonstrate that vegetal transport RNPs represent a new class of cytoplasmic RNP granule, termed Localization-bodies (L-bodies). We show that L-bodies are multiphase RNP granules, containing a dynamic protein-containing phase surrounding a non-dynamic RNA-containing substructure. Our results support a role for RNA as a critical scaffold component within these RNP granules and suggest thatcis-elements within localized mRNAs may drive subcellular RNA localization through control over phase behavior.

To investigate the origins and stages of vertebrate adaptive radiation, we reconstructed the spatial and temporal histories of genetic variants underlying major phenotypic axes of diversification from the genomes of 202 Caribbean pupfishes. Ancient standing variation from disparate spatial sources was reassembled into new combinations which are under strong selection for adaptation to novel trophic niches on only a single island throughout the Caribbean. This occurred in three stages: first, standing variation associated with feeding behavior swept, then standing variation regulating craniofacial development and pigmentation, and finally de novo variation for craniofacial development. Our results provide clear support for two longstanding hypotheses about adaptive radiation and demonstrate how ancient alleles maintained for millennia in distinct environmental refugia can be assembled into new adaptive combinations.One Sentence SummaryAncient origins of adaptive radiation

DNA-encoded library (DEL) technology has become a prominent screening platform in drug discovery owing to the capacity to screen billions or trillions of compounds in a single experiment. Although numerous successes with DEL technology have been reported, we are unaware of a rigorous examination of the many different variables that can influence a screen's success. Herein, we explore the impact of variable sample sequencing depth on the detection of tool compounds with known affinities toward a given target while simultaneously probing the effect of initial compound input. Our sequencing data confirm reports that high-affinity compounds can be discovered directly from a DEL screen, but we demonstrate that a mismatch between selection output and sequencing quantity can obscure useful ligands. Our results highlight the importance of selection coverage in grasping the entire picture of a DEL screen where the signal of a weak or underrepresented ligand may be suppressed by the inherent noise of a selection. These potential missed ligands may be critical to the success or failure of a drug discovery program.

BACKGROUND: Historically, limited sensitivity associated with traditional immunoassay methods have prevented the use of brain-specific proteins as blood biomarkers of traumatic brain injury (TBI) during triage, as these proteins exhibit low concentrations in circulation. Digital ELISA is a newly-developed technique that is up to 1000 times more sensitive than conventional ELISA methods. The purpose of this study was to determine whether the use of digital ELISA over conventional ELISA methods improves the performance of brain-specific proteins as blood biomarkers of TBI during triage. METHODS: Blood was sampled from TBI patients (n=13) at emergency department admission, as well as from neurologically normal controls (n=72). Serum levels of two brain-specific proteins, neurofilament light chain (NfL) and Tau, were measured via digital ELISA. Estimated conventional ELISA measures were generated by adjusting values according to the lower limits of detection achievable with commercially available conventional ELISA assays, and receiver characteristic analysis (ROC) was used to compare the diagnostic performance of digital ELISA measures to estimated conventional ELISA measures in terms of their ability to discriminate between TBI patients and controls. RESULTS: Used in combination, Digital ELISA measures of NfL and Tau could discriminate between groups with 100% sensitivity and 91.7% specificity. Estimated conventional ELISA measures could only discriminate between groups with 7.7% sensitivity and 94.4% specificity. This difference in diagnostic performance was statistically significant according to a comparison of areas under ROC curves. CONCLUSIONS: The use of digital ELISA over conventional ELISA methods improves the diagnostic performance of circulating brain-specific proteins for detection of TBI during triage.

2-Aminobenzimidazole cores are among the most common structural components in medicinal chemistry and can be found in many biologically active molecules. Herein, we report a mild protocol for the synthesis of multifunctional 2-aminobenzimidazoles on-DNA with broad substrate scopes. The reaction conditions expand our ability to design and synthesize 2-aminobenzimidazole core-focused DNA-encoded libraries.

Limited lower detection ranges associated with traditional immunoassay techniques have prevented the use of brain-specific proteins as blood biomarkers of stroke in the acute phase of care, as these proteins are often only present in circulation at low concentrations. Digital ELISA is a newly developed technique with allows for quantification of proteins in biofluids with up to 1000 times greater sensitivity than conventional ELISA techniques. The purpose of this study was to determine whether the extended lower limits of detection associated with digital ELISA could enable the use of brain-specific proteins as blood biomarkers of ischemic stroke during triage. Blood was sampled from ischemic stroke patients (n = 14) at emergency department admission, as well as from neurologically normal controls matched in terms of risk factors for cardiovascular disease (n = 33). Plasma levels of two brain-specific axonal proteins, neurofilament light chain (NfL) and tau, were measured via digital ELISA, and receiver-operating characteristic analysis was used to determine their ability to discriminate between groups. Plasma levels of NfL and tau were both significantly elevated in stroke patients versus controls, and could respectively discriminate between groups with 92.9% sensitivity / 84.9% specificity, and 85.7% sensitivity / 54.6% specificity. Furthermore, adjustment of measured NfL and Tau levels according to the lower-limits of detection associated with commercially-available conventional ELISA assays resulted in a dramatic and statistically significant decrease in diagnostic performance. Collectively, our results suggest that the increased analytical sensitivity of digital ELISA could enable the use of brain-specific proteins as blood biomarkers of ischemic stroke during triage.

The impacts of early ecological globalisation may have had profound economic and environmental consequences for human settlements and animal populations. Here, we review the extent of such historical impacts by investigating the medieval trade of walrus (Odobenus rosmarus rosmarus) ivory. We use an interdisciplinary approach including chaîne opératoire, ancient DNA (aDNA), stable isotope and zooarchaeological analysis of walrus rostra (skull sections) to identify their biological source and subsequent trade through Indigenous and urban networks. This approach complements and improves the spatial resolution of earlier aDNA observations, and we conclude that almost all medieval European finds of walrus rostra likely derived from Greenland. We further find that shifting urban nodes redistributed the traded ivory and that the latest medieval rostra finds were from smaller, often female, walruses of a distinctive DNA clade, which is especially prevalent in northern Greenland. Our results suggest that more and smaller animals were targeted at increasingly untenable distances, which reflects a classic pattern of resource depletion. We consider how the trade of walrus and elephant ivory intersected, and evaluate the extent to which emergent globalisation and the “resource curse” contributed to the abandonment of Norse Greenland. © 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

RNP granules are membrane-less compartments within cells, formed by phase separation, that function as regulatory hubs for diverse biological processes. However, the mechanisms by which RNAs and proteins interact to promote RNP granule structure and function in vivo remain unclear. In Xenopus laevis oocytes, maternal mRNAs are transported as large RNPs to the vegetal hemisphere of the developing oocyte, where local translation is critical for proper embryonic patterning. Here, we demonstrate that vegetal transport RNPs represent a new class of cytoplasmic RNP granule, termed Localization-bodies (L-bodies). We show that L-bodies are multiphase RNP granules, containing a dynamic protein-containing phase surrounding a non-dynamic RNA-containing substructure. Our results support a role for RNA as a critical scaffold component within these RNP granules and suggest that cis-elements within localized mRNAs may drive subcellular RNA localization through control over phase behavior.

Rationale Carbonised plant remains are analysed for reconstruction of past climates and agricultural regimes. Several recent studies have used C4 plants to address related questions, and correlations between modern C4 plant δ13 C values and rainfall have been found. The millets were important food crops in prehistoric Eurasia, yet little is known about causes of isotopic variation within millet species. Previous research has shown there to be significant isotopic variation between millet accessions. Here we compare isotope ratios from plants grown under different watering regimes. This allows for a consideration of whether or not Setaria italica is a good proxy for environmental reconstruction. Methods We compare stable isotope ratios of Setaria italica plants grown in a controlled environment chamber with different watering regimes. We compare the carbon isotope ratios of leaves and grains, and the nitrogen isotope ratios of grains, from 12 accessions of Setaria italica. Results We find significant isotopic variability between watering regimes. Carbon isotope ratios are positively correlated with water availability, and on average vary by 1.9‰ and 1.7‰ for leaves and grains, respectively. Grain nitrogen isotope ratios also vary with watering regime; however, the highest isotope ratios are found with the 130-mL watering regime. Conclusions The carbon isotope ratios of Setaria italica are strongly correlated with water availability. However, the correlation is the opposite to that seen in studies of C3 plants. The difference in isotopic ratio due to watering regime is comparable with that seen between different accessions; thus distinguishing between changing varieties of Setaria italica and changing climate is problematic. In terms of grain nitrogen isotope ratios, the highest δ15 N values were not associated with the lowest watering regime. Again, δ15 N variation is comparable with that which would be expected from an aridity effect or a manuring effect, and thus distinguishing between these factors is probably problematic.

This study investigates the performance, cost, and generating capacity impacts of switching from wet cooling towers to dry cooling systems to reduce the consumptive water use at existing fossil fuel-fired power plants in a water-stressed region. Retrofit analysis of dry cooling is conducted on a unit-by-unit basis for both coal-fired and gas-fired power plants. Unit-level results are then aggregated to the regional level. Based on regional averages, retrofitting dry cooling systems in lieu of wet cooling towers decreases total annual plant water consumption at existing coal- and gas-fired power plants by 93% and 100%, respectively, while increasing the levelized cost of electricity generation by approximately 12% and 18%, respectively. Based on a nominal regional water price, this cost increase corresponds to an average cost of consumptive water savings of $2.5 and $5.9 per cubic meter of water saved at coal and gas plants, respectively, if retrofit difficulty is minimal. Over the course of a year, the change in monthly net regional generating capacity from dry cooling retrofits exhibits a seasonal pattern, with the largest shortfalls occurring in July. The average monthly reduction in net capacity is estimated at 0.7% and 1.2% of the regional nameplate capacity for coal- and gas-based plants, respectively. Dry cooling retrofits thus lead to tradeoffs in water savings, cost, and capacity shortfalls, which vary with power plant characteristics. The tradeoffs identified here can fill existing knowledge gaps to better inform electric power industry water management policies, planning, and decision-making in water-stressed regions.

Oxygen isotope analysis (δ18O) of caprine and bovine tooth enamel carbonates from the Haua Fteah cave (Gebel Akhdar massif, northeast Libya) reveals significant differences in palaeoseasonality during the last c. 70 ka. Data indicate different phases of human occupation of the region occurred under notably different climatic conditions. During the last glacial period, prior to the Last Glacial Maximum, a gradual increase in climate aridity occurred. This was followed in the late glacial (c. 16.6–14.7 ka) by considerably more arid conditions and much greater climate seasonality, which was likely produced by changing winter precipitation amounts and a strengthening of arid summer air masses. The high seasonality in the late glacial coincides with a period when human activity at the Haua Fteah greatly intensified. Significant changes in subsistence strategies and the seasonal exploitation of food resources also occurred at this time. The results presented here suggest that changes in the seasonal climate may have affected the seasonal supply of floral and faunal resources available to local human populations at the time, which resulted in changing subsistence practices.

Gold catalysts for the hydrochlorination of acetylene are currently being studied as an environmentally benign replacement for industrial mercuric chloride catalysts, which undergo reduction and subsequent sublimation into the atmosphere. In this work the method of strong electrostatic adsorption was used with a cationic gold precursor to controllably deposit the gold precursors over a variety of activated carbon and metal oxide supports. The catalysts were characterized by XRD, STEM, and XPS before and after reaction or aging at temperature (180 °C) in HCl. The synthesis procedure resulted in highly dispersed Au nanoparticles (usually below the 1.5 nm limit of detection and some from 2 to 3 nm) over all supports. The series of catalysts exhibited an unusual relationship of sintering to activity; the catalysts which best anchored the Au crystallites were the least active; titania and silica catalysts showed almost no sintering and were virtually inactive, and even a graphitic carbon catalyst exhibited good anchoring but very poor activity. The sintering was caused by the HCl atmosphere and not the temperature; catalysts submitted to the reaction temperature in He were stable. It would appear that the metal nanoparticles, and Au at the edges of metal nanoparticles, are inactive. The current results support recent reports in the literature that the active sites are derived from isolated Au ions, but we can conclude that oxidized amorphous carbon also plays a key role in generating the active site. In this environment the active species is highly mobile and susceptible to sintering.

To achieve benefits similar to those seen in hybrid-/all-electric ground-based and marine vehicles, electric propulsion has been proposed for large commercial aircraft. Among the main drivers of this are improved fuel economy, reduced harmful emissions, and lower audible noise. In converting to electric propulsion, the added electrical components' masses must be minimised so that the benefits that the components enable - improved turbine efficiency, distributed propulsion and propulsion-airframe integration - are not cancelled out by their weight penalty. This puts stringent requirements on the large electric machines used in the system, both those that generate electric power from the turbine shaft and those that drive propellers or ducted fans, because they are among the heaviest of the added electric components. A key machine design metric in this application is the specific power (SP), or the power-to-mass ratio. This study gives a comprehensive overview of large electric machines for aircraft electric propulsion applications, with a focus on methods for mass reduction and SP improvement.

Talon cusps associated with permanent incisors are a rare occurrence but can cause numerous complications. When treatment is indicated options include radical or selective reduction of the accessory cusp, but there is no standard protocol for management. Study design: Patients referred to the Dublin Dental University Hospital for treatment of talon cusps were identified, contacted and consent obtained. Clinical notes, photographs and radiographs were retrospectively reviewed. Results: Eleven patients with 14 talon cusps were identified. The age ranged from 8–15 with a mean of 11 years. Four teeth had radical talon cusp reduction carried out and 10 teeth underwent selective reduction. Follow up ranged from 3–66 months. Technical information from these cases was used to devise a protocol for selective reduction. Conclusions: Selective reduction is a valuable technique for managing talon cusps. It is a conservative approach which can be employed before an incisor has reached maturity and is acceptable in young children.

Objective To examine the diagnostic accuracy of blood-based biomarkers for detecting Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). Methods Seven electronic databases were comprehensively searched for studies evaluating the diagnostic accuracy of blood-based biomarkers for detecting AD or aMCI up to July 31, 2020. The pooled sensitivity, specificity, and the diagnostic odds ratio (DOR) were calculated using a hierarchical summary receiver operating characteristic model. Results A total of 17 studies (n = 2,083) were included. In differentiating patients with AD from the controls, the DOR was 32.2 for the plasma Aβ42 (sensitivity = 88 %, specificity = 81 %), 29.1 for the plasma Aβ oligomer (sensitivity = 80 %, specificity = 88 %), and 52.1 for the plasma tau (sensitivity = 90 %, specificity = 87 %). For differentiating aMCI from the controls, the DOR was 60.4 for the plasma Aβ42 (sensitivity = 86 %, specificity = 90 %) and 49.1 for the plasma tau (sensitivity = 79 %, specificity = 94 %). The use of ultra-high sensitive technology explained the heterogeneity in the diagnostic performance of blood-based biomarkers (P = .01). Conclusions We suggest that blood-based biomarkers are minimally invasive and cost-effective tools for detecting AD; however, the evidence for detecting aMCI was still limited.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic RNA virus characterized by high transmission rates and pathogenicity worldwide. Continued control of the COVID-19 pandemic requires the diversification of rapid, easy to use, sensitive, and portable methods for SARS-CoV-2 sample preparation and analysis. Here, we propose a method for SARS-CoV-2 viral enrichment and enzymatic extraction of RNA from clinically relevant matrices in under 10 min. This technique utilizes affinity-capture hydrogel particles to concentrate SARS-CoV-2 from solution, and leverages existing PDQeX technology for RNA isolation. Characterization of our method is accomplished with reverse transcription real-time polymerase chain reaction (RT-PCR) for relative, comparative RNA detection. In a double-blind study analyzing viral transport media (VTM) obtained from clinical nasopharyngeal swabs, our sample preparation method demonstrated both comparable results to a routinely used commercial extraction kit and 100% concordance with laboratory diagnoses. Compatibility of eluates with alternative forms of analysis was confirmed using microfluidic RT-PCR (μRT-PCR), recombinase polymerase amplification (RPA), and loop-mediated isothermal amplification (LAMP). The alternative methods explored here conveyed successful amplification from all RNA eluates originating from positive clinical samples. Finally, this method demonstrated high performance within a saliva matrix across a broad range of viral titers and dilutions up to 90% saliva matrix, and sets the stage for miniaturization to the microscale., Graphical abstract Image 1

ObjectivesThe psychological impact of the COVID-19 pandemic on doctors is a significant concern. Due to the emergence of multiple pandemic waves, longitudinal data on the impact of COVID-19 are vital to ensure an adequate psychological care response. The primary aim was to assess the prevalence and degree of psychological distress and trauma in frontline doctors during the acceleration, peak and deceleration of the COVID-19 first wave. Personal and professional factors associated with psychological distress are also reported.DesignA prospective online three-part longitudinal survey.SettingAcute hospitals in the UK and Ireland.ParticipantsFrontline doctors working in emergency medicine, anaesthetics and intensive care medicine during the first wave of the COVID-19 pandemic in March 2020.Primary outcome measuresPsychological distress and trauma measured using the General Health Questionnaire-12 and the Impact of Events-Revised.ResultsThe initial acceleration survey distributed across networks generated a sample of 5440 doctors. Peak and deceleration response rates from the original sample were 71.6% (n=3896) and 56.6% (n=3079), respectively. Prevalence of psychological distress was 44.7% (n=1334) during the acceleration, 36.9% (n=1098) at peak and 31.5% (n=918) at the deceleration phase. The prevalence of trauma was 23.7% (n=647) at peak and 17.7% (n=484) at deceleration. The prevalence of probable post-traumatic stress disorder was 12.6% (n=343) at peak and 10.1% (n=276) at deceleration. Worry of family infection due to clinical work was the factor most strongly associated with both distress (R2=0.06) and trauma (R2=0.10).ConclusionFindings reflect a pattern of elevated distress at acceleration and peak, with some natural recovery. It is essential that policymakers seek to prevent future adverse effects through (a) provision of vital equipment to mitigate physical and psychological harm, (b) increased awareness and recognition of signs of psychological distress and (c) the development of clear pathways to effective psychological care.Trial registration numberISRCTN10666798.

PurposeOur group recently identified a ten gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population.MethodsPublically available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 hours post-symptom onset, along with 23 cardiovascular disease controls were obtained via the National Center for Biotechnology Information Gene Expression Omnibus. Expression levels of the ten candidate genes were extracted, compared between groups, and evaluated for their discriminatory ability at each time point.ResultsWe observed a largely identical pattern of differential expression between stroke patients and controls across the ten candidate genes as reported in our prior work. Furthermore, the coordinate expression levels of the ten candidate genes were able to discriminate between stroke patients and controls with levels of sensitivity and specificity upwards of 90% across all three time points.ConclusionsThese findings confirm the diagnostic robustness of the previously identified pattern of differential expression in independent patient population, and further suggest that it is temporally stable over the first 24 hours of stroke pathology.

NEW FINDINGS What is the central question of this study? Does a stroke event influence aortic endothelial function; and what is the role of peripheral circulating leucocytes in stroke on the vascular reactivity of the aorta? What is the main finding and its importance? In vitro co-culture experiments demonstrated that aortic endothelium-dependent relaxation was impaired when rat aortic rings were co-cultured with leucocytes stimulated with serum from stroke patients. Impaired vascular reactivity was not observed in aortic rings without leucocytes stimulated with serum from stroke patients or age-matched control patients with or without leucocytes. These data suggest that leucocyte-dependent altered aortic endothelium-dependent relaxation with stroke and the systemic consequences of stroke on vascular inflammation may occur in the aorta. Post-stroke inflammation has been linked to poor stroke outcomes. The vascular endothelium senses and responds to circulating factors, in particular inflammatory cytokines. Although stroke-associated local cerebrovascular dysfunction is well reported, the effects of a stroke on conduit artery function are not fully understood. We tested the hypothesis that serum from stroke patients triggers leucocyte-dependent aortic endothelial dysfunction that is associated with elevated concentrations of cytokines. Total leucocytes were isolated from healthy individuals, and the cells were incubated in serum from control subjects or stroke patients for 6 h. The quantity of cytokines in media was determined using an immunoassay. Vascular reactivity was determined by the rat aortic rings that were co-cultured with or without leucocytes and stimulated with serum samples from control subjects or stroke patients. Endothelium-dependent dilatation was significantly impaired in aortic rings co-cultured with leucocytes plus serum from stroke patients (50 ± 30 versus 85 ± 13%, P

The nature of subsistence strategies employed by the past inhabitants of Amazonia has been a widely debated topic, however little evidence has been found so far in order to support some of the proposed hypotheses. This article contributes to this debate by presenting new δ13C and δ15N data from the human populations that occupied the Maraca region of the mouth of the Amazon river, around 500 BP (years before present). It directly compares these newly generated results to previously published human isotope data from neighbouring Marajo Island (Marajoara phase, 1600 to 700 BP), as well as other areas in the lowland Neotropics, in an attempt to build a bigger picture of the dietary habits of the Lower Amazon pre-colonial populations. The overall results suggest that the populations that occupied the mouth of the Amazon after 2000 BP had diets based on the exploitation of fish and a wide range of C3 plant resources, as well as possibly having a minor C4 or CAM component. The data presented are also consistent with an emerging consensus that there was no single adaptive pattern for ancient Amazonian populations and proposes that diversified economic strategies based on wild and cultivated plants combined with the exploitation of faunal resources could have developed over time and sustained long-term successful patterns of human occupations.

Objective: The objective of this work was to assess the ability of peripheral blood cell-free DNA (cfDNA) levels to identify ischaemic stroke early in the acute phase of care, as well as to examine the relationship between peripheral blood cfDNA levels and stroke-induced innate immune system activation. Methods: Upon emergency department admission, peripheral blood samples were obtained from 43 patients experiencing acute ischaemic stroke and 20 patients identified as stroke mimics. Plasma cfDNA levels were measured using quantitative polymerase chain reaction (qPCR), infarct volume and NIH stroke scale (NIHSS) were used to assess injury severity, and peripheral blood neutrophil count was used as a measure of innate immune system status.Results: Peripheral blood cfDNA levels were significantly elevated in patients suffering stroke relative to those diagnosed as stroke mimics, and could differentiate between groups with 86% (95% CI = 72–95%) sensitivity and 75% (95% CI = 51–91%) specificity. Furthermore, cfDNA levels displayed significant positive associations between both infarct volume and peripheral blood neutrophil count within the stroke group. Conclusions: These findings suggest that assessment of peripheral blood cfDNA levels may be useful for the identification of ischaemic stroke in the acute care setting, and provide associative evidence that cfDNA is a potential activator of the peripheral innate immune system in response to cerebral ischaemia.

In the late 1920s, R. H. Park published a change of variables that provided a means of analyzing the performance of synchronous machines. He transformed the stator variables to substitute variables that eliminated the rotor-position-dependent terms from the self- and mutual inductances. This transformation has become the bedrock of machine analysis and simulation; however, Park's derivation involves a maze of three-phase trigonometric identities with generator action and we are left searching for a more concise analytical development. In this paper, a direct connection is established between Tesla's rotating magnetic field and reference frame theory. In particular, an analytical basis for the change of variables is established from the expression of Tesla's rotating magnetic field combined with an expression that relates stationary and rotating coordinates. This leads directly to reference frame theory and an array of transformations that yield the same advantages as Park's transformation. It shows that all transformations used in the analysis of power systems, electric machines, and drive systems have a common origin. Also, the magnetic poles can be analytically located during transient operation and on a phasor diagram during steady-state operation, thereby providing a vivid visualization of machine and drive operation.

In this study we compare carbon isotope values in modern Helix melanostoma shell carbonate (δ13Cshell) from the Gebel al-Akhdar region of Libya with carbon isotope values in H. melanostoma body tissue (δ13Cbody), local vegetation (δ13Cplant) and soil (δ13Csoil). All vegetation in the study area followed the C3 photosynthetic pathway. However, the δ13Cplant values of different species formed two distinct isotopic groups. This can be best explained by different water use efficiencies with arid adapted species having significantly more positive δ13Cplant values than less water efficient species. The ranges and means of δ13Cbody and δ13Cplant were statistically indistinguishable from one another suggesting that δ13Cbody was primarily a function of local vegetation composition. H. melanostoma δ13Cshell reflected the δ13Cplant of local vegetation with a positive offset between body/diet and shell of 14.5 ± 1.4‰. Therefore, in the Gebel al-Akhdar where only C3 plants are present, higher mean δ13Cshell values likely reflect greater abundances of water-efficient C3 plants in the snails diet and therefore in the landscape, whilst lower mean δ13Cshell values likely reflect the consumption of less water-efficient C3 plants. The distribution of these plants is in turn affected by environmental factors such as rainfall. These findings can be applied to archaeological and geological shell deposits to reconstruct late Pleistocene to Holocene vegetation change in the southeast Mediterranean.

BackgroundDetection of brain-specific miRNAs in the peripheral blood could serve as a surrogate marker of traumatic brain injury (TBI). Here, we systematically identified brain-enriched miRNAs, and tested their utility for use as TBI biomarkers in the acute phase of care.MethodsPublically-available microarray data generated from 31 postmortem human tissues was used to rank 1,364 miRNAs in terms of their degree of brain-specific expression. Levels of the top five ranked miRNAs were then prospectively measured in serum samples collected from 10 TBI patients at hospital admission, as well as from 10 controls.ResultsThe top five miRNAs identified in our analysis (miR-137, miR-219a-5p, miR-128-3p, miR-124-3p, and miR-138-5p) exhibited 31 to 74-fold higher expression in brain relative to other tissues. Furthermore, their levels were elevated in serum from TBI patients compared to controls, and were collectively able to discriminate between groups with 90% sensitivity and 80% specificity. Subsequent informatic pathway analysis revealed that their target transcripts were significantly enriched for components of signaling pathways which are active in peripheral organs such as the heart.ConclusionsThe five candidate miRNAs identified in this study have promise as blood biomarkers of TBI, and could also be molecular contributors to systemic physiologic changes commonly observed post-injury.A FINAL PEER REVIEWED VERSION OF THIS ARTICLE HAS BEEN PUBLISHED IN BRAIN INJURY AT THE FOLLOWING DOI: 10.1080/02699052.2020.1764102There are some notable differences between the analysis presented in this preprint and our final peer-reviewed article. There was a single tissue sample originating from spinal cord that we had classified as a non-brain tissue in our original analysis outlined in this preprint. Because the composition of spinal cord and brain are highly similar in terms of gene expression, classifying this sample as a non-brain tissue dramatically reduced the levels of brain enrichment observed in the analysis. Because brain and spinal cord are molecularly highly similar, but technically distinct anatomical structures, we simply decided to exclude this sample from our final analysis published in Brain Injury to avoid confounds. The top 5 miRNAs identified in our original analysis still fell within the top 7 of this final analysis. In addition, the final analysis identified two additional miRNAs which could be candidate biomarkers based on levels of brain enrichment.The final article published in Brain Injury also reports an additional confirmatory tissue specificity analysis performed in a second independent dataset, as well as additional analysis examining the brain specificity of several notable previously proposed miRNA TBI biomarkers, which is not described in this preprint.