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The use of group work projects is common in introductory statistics courses, including projects where students collect their own data. However, the COVID-induced lockdown at the start of 2020 meant that data collection was compromised. In this study, we examine a situation where students were permitted to use artificial (made-up) data for their project during the COVID lockdown. We examine features of these project reports and the data the students used before, during and after the lockdown. We find evidence that during-COVID projects (based on artificial data) were more likely to study people but less likely to involve interaction with people, and were less likely to require t-tests for analysis. We also found that the artificial data were less likely to include outliers, but no evidence that the artificial data were contrived to produce 'small' p values.

In this note we demonstrate two instances where matrix multiplication can be easily verified. In the first setting, the matrix product appears as matrix element concatenation, and in the second, the product coincides with matrix addition. General proofs for some results are provided with a more complete description for 2×2 matrices. Suggested for consolidation of the algorithm rather than as an introduction, we believe the example base that can be created, combined with an analysis for understanding the context, acts as a positive motivator to secure mastery as it needs to be practised.

Gay men report poorer body image than straight men, but no research has examined other dimensions of sexual identity (e.g., sexual attraction). Most research also focused on clinical outcomes of body dissatisfaction rather than subclinical influences on quality of life. We examined the association between sexual attraction (i.e., attraction to men or women), body dissatisfaction and quality of life in cisgender men. We hypothesised that: 1) men attracted to men would report higher body dissatisfaction, 2) men attracted to men would report lower quality of life (i.e., psychological, physiological, social, and environmental), 3) body dissatisfaction would be negatively associated with quality of life, and finally 4) body dissatisfaction mediates the association between sexual attraction and quality of life. A cross-sectional study (86 men attracted to men and 87 men attracted to women) supported these hypotheses but showed that sexual attraction was only associated with psychological quality of life. While sexual attraction was only associated with psychological quality of life, there were indirect associations with all quality of life domains acting through body dissatisfaction. Our findings emphasise that men attracted to men are at greater risk of poor body image and that body dissatisfaction is a pervasive health problem, negatively influencing subclinical health and well-being in cisgender men. We also highlight how body dissatisfaction may be one psychological process negatively influencing the psychological quality of life in men attracted to men. More resources should be directed toward preventing body dissatisfaction, particularly in sexual minoritised men.

Objective: This study aimed to compare microvascular Doppler sonography (MDS) and laser speckle contrast imaging (LSCI) for assessing vessel patency and aneurysm occlusion during microsurgical clipping of intracranial aneurysms. Methods: MDS and LSCI were used after clip placement during six neurovascular procedures including six patients, and agreement between the two techniques was assessed. LSCI was performed in parallel or right after MDS evaluation. The Doppler response was assessed through listening while flow in the LSCI videos was evaluated by three blinded neurovascular surgeons after the surgery. Statistical analysis determined the agreement between the techniques in assessing flow in 18 regions of interest (ROIs). Results: Agreement between MDS and LSCI in assessing vessel patency was observed in 87 % of the ROIs. LSCI accurately identified flow in 93.3 % of assessable ROIs, with no false positive or negative measurements. Three ROIs were not assessable with LSCI due to motion artifacts or poor image quality. No complications were observed. Conclusions: LSCI demonstrated high agreement with MDS in assessing vessel patency during microsurgical clipping of intracranial aneurysms. It provided continuous, real-time, full-field imaging with high spatial resolution and temporal resolution. While MDS allowed evaluation of deep vascular regions, LSCI complemented it by offering unlimited assessment of surrounding vessels.

Abstract Stroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury. Here, we characterize the identity of cells arising from the SVZ after stroke and uncover a mechanism through which they facilitate neural repair and functional recovery. With genetic lineage tracing, we show that SVZ-derived cells that migrate towards cortical photothrombotic stroke in mice are predominantly undifferentiated precursors. We find that ablation of neural precursor cells or conditional knockout of VEGF impairs neuronal and vascular reparative responses and worsens recovery. Replacement of VEGF is sufficient to induce neural repair and recovery. We also provide evidence that CXCL12 from peri-infarct vasculature signals to CXCR4-expressing cells arising from the SVZ to direct their ectopic migration. These results support a model in which vasculature surrounding the site of injury attracts cells from the SVZ, and these cells subsequently provide trophic support that drives neural repair and recovery.

Abstract Background Recovery after surgery intersects physical, psychological, and social domains. In this study we aim to assess the feasibility and usability of a mobile health application called PositiveTrends to track recovery in these domains amongst participants undergoing hip, knee arthroplasty or spine surgery. Our secondary aim was to generate procedure-specific, recovery trajectories within the pain and medication, psycho-social and patient-reported outcomes domain. Methods Prospective, observational study in participants greater than eighteen years of age. Data was collected prior to and up to one hundred and eighty days after completion of surgery within the three domains using PositiveTrends. Feasibility was assessed using participant response rates from the PositiveTrends app. Usability was assessed quantitatively using the System Usability Scale. Heat maps and effect plots were used to visualize multi-domain recovery trajectories. Generalized linear mixed effects models were used to estimate the change in the outcomes over time. Results Forty-two participants were enrolled over a four-month recruitment period. Proportion of app responses was highest for participants who underwent spine surgery (median = 78, range = 36–100), followed by those who underwent knee arthroplasty (median = 72, range = 12–100), and hip arthroplasty (median = 62, range = 12–98). System Usability Scale mean score was 82 ± 16 at 180 days postoperatively. Function improved by 8 and 6.4 points per month after hip and knee arthroplasty, respectively. In spine participants, the Oswestry Disability Index decreased by 1.4 points per month. Mood improved in all three cohorts, however stress levels remained elevated in spine participants. Pain decreased by 0.16 (95% Confidence Interval: 0.13–0.20, p

Whale mortality and strandings have increased in recent years, with deceased whales often brought to landfill. However, the disposal of whale remains offshore holds significant ecological importance and can be a culturally and ethically sensitive approach. Moreover, offshore disposal mitigates potential risks associated with onshore whale remains disposal, such as the spread of diseases and the logistical challenges of managing large carcasses. A challenge with offshore disposal is defining the best release location to avoid the remains drifting ashore or into shipping channels. Here we compared the drift model outputs using a drift forecast model (SARMAP) for a 14 m whale carcass that was moved offshore in southeast Queensland, Australia, and fitted with a satellite tracker over an observation period of 150 h until positioning signal ceased. The modelling was conducted using different ocean products (BLUElink, HYCOM, and Copernicus), which showed a good agreement with the tracked whale carcass, albeit with changing wind conditions and contrasting currents flowing northward along the coast and, further offshore, flowing south. This case study illustrated that wind was the foremost driver of carcass drift due to the surface area above the water surface. The drift forecast simulations allowed for a reliable prediction of the floating whale drift that can assist authorities with decision making. Offshore disposal of whale carcasses is a sustainable practice but requires good planning and scientific assessment.

BackgroundPatients with spontaneous and traumatic intracranial hemorrhage (ICH) are frequently transfused platelets to treat thrombocytopenia, platelet function defects, and reverse antiplatelet drugs. ABO-identical platelet transfusion has been suggested to lead to higher post-transfusion platelet increments compared to major-ABO incompatible transfusion. We hypothesized that patients who received ABO-identical transfusion would have higher post-transfusion platelet increments and superior neurologic outcomes.MethodsAdults with traumatic or non-traumatic ICH from January 1st 2018 to December 31st 2022 were identified using electronic medical records and international classification of disease (ICD)-10 codes. Patients were excluded if they lacked a platelet count within 24 hours before and within 24 hours after transfusion or if they received multiple platelet transfusions before their platelet count was remeasured. After stratification by ABO-identical, ABO-major incompatible, and ABO-minor incompatible transfusion, post transfusion increments were compared, as were clinical outcomes.ResultsAmong 167 patients who received platelet transfusion, 76 (45.5%) received ABO-identical transfusion, 54 (32.3%) received ABO-major incompatible transfusion, and 37 (22.2%) received ABO-minor incompatible transfusion. There were no significant differences in absolute platelet increment between groups. The median increment was 7x109/L for ABO-identical platelets, 10x109/L for ABO-major incompatible platelets, and 11x109/L for ABO-minor incompatible platelets, p = .87. There was no significant difference in the percentage of patients discharged alive with modified Rankin score of 1 or 2 or cerebral performance category 1 or 2 between groups (p = .56 and .39 respectively). After adjusting for confounders in a general linear model there remained no associations between ABO compatibility and platelet increment after transfusion.ConclusionsOur data support similar efficacy for ABO-identical and ABO-incompatible platelet transfusion in patients with ICH.

Abstract B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma.

AVM surgery is challenging due to progressive and often unforeseeable flow changes during its resection which involve both the AVM and the surrounding brain tissue. Hence, accurate monitoring of blood flow is crucial to minimize complications and improve outcomes. The following case report illustrates the usefulness of complimentary non-invasive tools that can provide real time blood flow assessment. We present a case demonstrating the application of laser speckle contrast imaging (LSCI) in evaluating vessel flow dynamics during AVM surgery. A 30-year-old female presented with sudden headaches, nausea, vomiting, and vertigo. Emergency imaging revealed a ruptured cerebellar AVM necessitating surgical intervention. LSCI was integrated into the surgical workflow, providing continuous visualization of relative cerebral blood flow (rCBF) of vessels surrounding the AVM. Before AVM resection, LSCI measurements revealed the arterialized vasculature supplying the AVM nidus; measurements after AVM resection showed significant hemodynamic changes including normal flow in the initially arterialized AVM draining veins and adjacent arterial branches. LSCI also detected blood flow alterations during temporary occlusion, enabling assessment of downstream vascular regions. In conclusion, we provide an example supporting the utility of LSCI for real-time hemodynamic monitoring during AVM resection surgery. LSCI offers non-invasive, continuous, and immediate blood flow information, complementing conventional imaging methods like indocyanine green angiography. Additionally, our findings suggest that LSCI has the potential to provide a non-invasive means of identifying the specific superficial vessel branches or cortical areas that receive blood supply from a particular vessel.

“Screening” is a search for preclinical, asymptomatic disease, including cancer. Widespread cancer screening has led to large increases in early-stage cancers and pre-cancers. Ubiquitous public messages emphasize the potential benefits to screening for these lesions based on the underlying assumption that treating cancer at early stages before spread to other organs should make it easier to treat and cure, using more tolerable interventions. The intuition is so strong that public campaigns are sometimes launched without conducting definitive trials directly comparing screening to usual care. An effective cancer screening test should not only increase the incidence of early-stage preclinical disease but should also decrease the incidence of advanced and metastatic cancer, as well as a subsequent decrease in cancer-related mortality. Otherwise, screening efforts may be uncovering a reservoir of non-progressive and very slowly progressive lesions that were not destined to cause symptoms or suffering during the person's remaining natural lifespan: a phenomenon known as “overdiagnosis.” We provide here a qualitative review of cancer overdiagnosis and discuss specific examples due to extensive population-based screening, including neuroblastoma, prostate cancer, thyroid cancer, lung cancer, melanoma, and breast cancer. The harms of unnecessary diagnosis and cancer therapy call for a balanced presentation to people considering undergoing screening, even with a test of accepted benefit, with a goal of informed decision-making. We also discuss proposed strategies to mitigate the adverse sequelae of overdiagnosis.

A potential method for tracking neurovascular disease progression over time in preclinical models is multiphoton fluorescence microscopy (MPM), which can image cerebral vasculature with capillary-level resolution. However, obtaining high-quality, three-dimensional images with traditional point scanning MPM is time-consuming and limits sample sizes for chronic studies. Here, we present a convolutional neural network-based (PSSR Res-U-Net architecture) algorithm for fast upscaling of low-resolution or sparsely sampled images and combine it with a segmentation-less vectorization process for 3D reconstruction and statistical analysis of vascular network structure. In doing so, we also demonstrate that the use of semi-synthetic training data can replace the expensive and arduous process of acquiring low- and high-resolution training pairs without compromising vectorization outcomes, and thus open the possibility of utilizing such approaches for other MPM tasks where collecting training data is challenging. We applied our approach to images with large fields of view from a mouse model and show that our method generalizes across imaging depths, disease states and other differences in neurovasculature. Our pretrained models and lightweight architecture can be used to reduce MPM imaging time by up to fourfold without any changes in underlying hardware, thereby enabling deployability across a range of settings.

ObjectiveTo compare efficacy of oral versus intravenous (IV) methadone on postoperative pain and opioid requirements after spine surgery.MethodsThis was a retrospective, single-academic center cohort study evaluating 1010 patients who underwent >3 level spine surgery from January 2017 to May 2020 and received a one-time dose of oral or intravenous methadone prior to surgery. The primary outcome measured was postoperative opioid use in oral morphine equivalents (ME) and verbal response scale (VRS) pain scores up to postoperative day (POD) three. Secondary outcomes were time to first bowel movement and adverse effects (reintubation, myocardial infarction, and QTc prolongation) up to POD 3.ResultsA total of 687 patients received oral and 317 received IV methadone, six patients were excluded. The IV group received a significantly greater methadone morphine equivalent (ME) dose preoperatively (112.4 ± 83.0 mg ME versus 59.3 ± 60.9 mg ME, p < 0.001) and greater total (methadone and non-methadone) opioid dose (119.1 ± 81.4 mg ME versus 63.9 ± 62.5 mg ME, p < 0.001), intraoperatively. Although pain scores for the oral group were non-inferior to the IV group for all postoperative days (POD), non-inferiority for postoperative opioid requirements was demonstrated only on POD 3. Based on the joint hypothesis for the co-primary outcomes, oral methadone was non-inferior to IV methadone on POD 3 only. No differences in secondary outcomes, including QTc prolongation and arrhythmias, were noted between the groups.ConclusionsOral methadone is a feasible alternative to IV methadone for patients undergoing spine surgery regarding both pain scores and postoperative opioid consumption.

Plain English summary Health data from routine care can be pseudonymised (with a link remaining to the patient but identifying features removed) or anonymised (with identifying features removed and the link to the patient severed) and used for research and health planning; termed “secondary use”. The National Health Service (NHS) is a single publicly-funded health service for the United Kingdom (UK). The NHS supports secondary data use with a National Data opt-out system. The potential benefits of data secondary use are clear but concerns have been raised. Although the Data Opt-Out is publicised, it is unclear how much public awareness there is of this scheme. We report a patient and publicly created and delivered series of activities including > 350 people; with young adults, patients, NHS staff and the public; to assess concerns, knowledge and acceptance of data sharing. Perceptions of and support for secondary health data use varied depending on who was asked (by age, gender) and their experience of health services (Staff member, patient, member of the public). Knowledge of schemes to limit secondary data use (such as the UK National Data Op-Out) was low, even among NHS staff. The main concerns of sharing health data included onward data use, the potential for discrimination and exploitation and commercial gain from data use with no benefit to patients. Despite this, most participants agreed with health data sharing with NHS, academic and commercial health-based entities. Agreed, co-created themes to increase the acceptability of health data secondary use included education about ‘Opt-out’ schemes, health service oversight of data use (as the most trusted partner), public and patient involvement in data sharing decisions and public transparency.

An expansion of bioenergy has been proposed to help reduce fossil-fuel greenhouse gas emissions, and short-rotation forestry (SRF) can contribute to this expansion. However, SRF plantations could also be sources of biogenic volatile organic compound (BVOC) emissions, which can impact atmospheric air quality. In this study, emissions of isoprene and 11 monoterpenes from the branches and forest floor of hybrid aspen, Italian alder and Sitka spruce stands in an SRF field trial in central Scotland were measured during two years (2018–2019) and used to derive emission potentials for different seasons. Sitka spruce was included as a comparison as it is the most extensive plantation species in the UK. Winter and spring emissions of isoprene and monoterpenes were small compared to those in summer. Sitka spruce had a standardised mean emission rate of 15 µgCg-1h-1 for isoprene in the dry and warm summer of 2018 – more than double the emissions in 2019. However, standardised mean isoprene emissions from hybrid aspen were similar across both years, approximately 23 µgCg-1h-1, and standardised mean isoprene emissions from Italian alder were very low. Mean standardised total monoterpene emissions for these species followed a similar pattern of higher standardised emissions in the warmer year: Sitka spruce emitting 4.5 and 2.3 µgCg-1h-1 for 2018 and 2019, aspen emitting 0.3 and 0.09 µgCg-1h-1, and Italian alder emitting 1.5 and 0.2 µgCg-1h-1, respectively. In contrast to these foliage emissions, the forest floor was only a small source of monoterpenes, typically 1 or 2 orders of magnitude lower than foliage emissions on a unit of ground area basis. Estimates of total annual emissions from each plantation type per hectare were derived using the MEGAN 2.1 model. The modelled total BVOC (isoprene and monoterpenes) emissions of SRF hybrid aspen plantations were approximately half those of Sitka spruce for plantations of the same age. Italian alder SRF emissions were 20 times smaller than from Sitka spruce. The expansion of bioenergy plantations to 0.7 Mha has been suggested for the UK to help achieve net-zero greenhouse gas emissions by 2050. The model estimates show that, with such an expansion, total UK BVOC emissions would increase between % and 35 %, depending on the tree species planted. Whereas increases might be small on a national scale, regional increases might have a larger impact on local air quality.

Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both Zaire Ebolavirus (EBOV) and COVID-19 patient cohorts. We also show unique characteristics absent in Respiratory Syncytial Virus or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risk off-target effects.

ABSTRACT Interbacterial competition is prevalent in host-associated microbiota, where it can shape community structure and function, impacting host health in both positive and negative ways. However, the factors that permit bacteria to discriminate among their various neighbors for targeted elimination of competitors remain elusive. We identified a putative lipoprotein (TasL) in Vibrio species that mediates cell-cell attachment with a subset of target strains, allowing inhibitors to target specific competitors for elimination. Here, we describe this putative lipoprotein, which is associated with the broadly distributed type VI secretion system (T6SS), by studying symbiotic Vibrio fischeri, which uses the T6SS to compete for colonization sites in their squid host. We demonstrate that TasL allows V. fischeri cells to restrict T6SS-dependent killing to certain genotypes by selectively integrating competitor cells into aggregates while excluding other cell types. TasL is also required for T6SS-dependent competition within juvenile squid, indicating that the adhesion factor is active in the host. Because TasL homologs are found in other host-associated bacterial species, this newly described cell-cell attachment mechanism has the potential to impact microbiome structure within diverse hosts. IMPORTANCE T6SSs are broadly distributed interbacterial weapons that share an evolutionary history with bacteriophage. Because the T6SS can be used to kill neighboring cells, it can impact the spatial distribution and biological function of both free-living and host-associated microbial communities. Like their phage relatives, T6SS+ cells must sufficiently bind competitor cells to deliver their toxic effector proteins through the syringe-like apparatus. Although phage use receptor-binding proteins (RBPs) and tail fibers to selectively bind prey cells, the biophysical properties that mediate this cell-cell contact for T6SS-mediated killing remain unknown. Here, we identified a large, predicted lipoprotein that is coordinately expressed with T6SS proteins and facilitates the contact that is necessary for the T6SS-dependent elimination of competitors in a natural host. Similar to phage RBPs and tail fibers, this lipoprotein is required for T6SS+ cells to discriminate between prey and nonprey cell types, revealing new insight into prey selection during T6SS-mediated competition.

Objective This was a retrospective, cohort study investigating the efficacy and safety of continuous low-dose postoperative tranexamic acid (PTXA) on drain output and transfusion requirements following adult spinal deformity surgery. Methods One hundred forty-seven patients undergoing posterior instrumented thoracolumbar fusion of ≥ 3 vertebral levels at a single institution who received low-dose PTXA infusion (0.5–1 mg/kg/hr) for 24 hours were compared to 292 control patients who did not receive PTXA. The cohorts were propensity matched based on age, sex, American Society of Anesthesiologist physical status classification, body mass index, number of surgical levels, revision surgery, operative duration, and total intraoperative TXA dose (n = 106 in each group). Primary outcome was 72-hour postoperative drain output. Secondary outcomes were number of allogeneic blood transfusions. Results There was no significant difference in postoperative drain output in the PTXA group compared to control (660 ±420 mL vs. 710 ±490 mL, p = 0.46). The PTXA group received significantly more crystalloid (6,100 ±3,100 mL vs. 4,600 ±2,400 mL, p < 0.001) and red blood cell transfusions postoperatively (median [interquartile range]: 1 [0–2] units vs. 0 [0–1] units; incidence rate ratio [95% confidence interval], 1.6 [1.2–2.2]; p = 0.001). Rates of adverse events were comparable between groups. Conclusion Continuous low-dose PTXA infusion was not associated with reduced drain output after spinal deformity surgery. No difference in thromboembolic incidence was observed. A prospective dose escalation study is warranted to investigate the efficacy of higher dose PTXA.

Recent advances in two-photon fluorescence microscopy (2PM) have allowed large scale imaging and analysis of blood vessel networks in living mice. However, extracting network graphs and vector representations for the dense capillary bed remains a bottleneck in many applications. Vascular vectorization is algorithmically difficult because blood vessels have many shapes and sizes, the samples are often unevenly illuminated, and large image volumes are required to achieve good statistical power. State-of-the-art, three-dimensional, vascular vectorization approaches often require a segmented (binary) image, relying on manual or supervised-machine annotation. Therefore, voxel-by-voxel image segmentation is biased by the human annotator or trainer. Furthermore, segmented images oftentimes require remedial morphological filtering before skeletonization or vectorization. To address these limitations, we present a vectorization method to extract vascular objects directly from unsegmented images without the need for machine learning or training. The Segmentation-Less, Automated, Vascular Vectorization (SLAVV) source code in MATLAB is openly available on GitHub. This novel method uses simple models of vascular anatomy, efficient linear filtering, and vector extraction algorithms to remove the image segmentation requirement, replacing it with manual or automated vector classification. Semi-automated SLAVV is demonstrated on three in vivo 2PM image volumes of microvascular networks (capillaries, arterioles and venules) in the mouse cortex. Vectorization performance is proven robust to the choice of plasma- or endothelial-labeled contrast, and processing costs are shown to scale with input image volume. Fully-automated SLAVV performance is evaluated on simulated 2PM images of varying quality all based on the large (1.4×0.9×0.6 mm3 and 1.6×108 voxel) input image. Vascular statistics of interest (e.g. volume fraction, surface area density) calculated from automatically vectorized images show greater robustness to image quality than those calculated from intensity-thresholded images.

Middle Ordovician phosphatic ironstone of the Welsh Basin provides new insight into the paleoenvironmental significance of ironstone and Ordovician ocean chemistry. Deposition occurred in a back-arc basin along the southern margin of Avalonia as the Rheic Ocean opened to the south. Ironstone is interpreted to have accumulated as part of an aggradational parasequence on a storm-dominated shelf with coastal upwelling. This parasequence has a laminated pyritic mudstone base that grades upward into variably bioturbated mudstone and coated grain-rich, intraclastic ironstone, which is overlain in turn by cross-stratified grainstone composed entirely of coated Fe grains. A coarser clastic parasequence composed of more proximal lithofacies rests conformably above and suggests the contact between the two parasequences is a maximum flooding surface marking the onset of highstand conditions. Lithofacies associations suggest that sustained coastal upwelling created a wedge of nutrient-rich, ferruginous seawater on the middle shelf that stimulated high surface ocean productivities. Large, coated Fe grains (granule size) composed of discontinuous and concentric carbonate fluorapatite, hematite, and chamosite cortical layers record fluctuations in pore water Eh that are interpreted to have been related to changes in upwelling intensity and intermittent storm reworking of the seafloor. Results support an emerging model for Ordovician ironstone underpinned by the development of ferruginous bottom water that was periodically tapped by coastal upwelling. Expanding, semi-restricted seaways such as the Rheic Ocean were ideal locations for the ponding of this anoxic, hydrothermally enriched seawater, especially during the early Paleozoic when the deep ocean was variably and inconsistently oxygenated. The coincidence of ironstone depositional episodes with graptolite diversification events suggests that, in addition to Fe, the sustained supply of upwelling-related P may have driven the radiation of some planktonic ecosystems during the Great Ordovician Biodiversification Event. Concomitant minor extinctions of benthic trilobites occurred as these ferruginous waters impinged on the shelf.

Separation of B cells into different subsets has been useful to understand their different functions in various immune scenarios. In some instances, the subsets defined by phenotypic FACS separation are relatively homogeneous and so establishing the functions associated with them is straightforward. Other subsets, such as the “Double negative” (DN, CD19+CD27-IgD-) population, are more complex with reports of differing functionality which could indicate a heterogeneous population. Recent advances in single-cell techniques enable an alternative route to characterize cells based on their transcriptome. To maximize immunological insight, we need to match prior data from phenotype-based studies with the finer granularity of the single-cell transcriptomic signatures. We also need to be able to define meaningful B cell subsets from single cell analyses performed on PBMCs, where the relative paucity of a B cell signature means that defining B cell subsets within the whole is challenging. Here we provide a reference single-cell dataset based on phenotypically sorted B cells and an unbiased procedure to better classify functional B cell subsets in the peripheral blood, particularly useful in establishing a baseline cellular landscape and in extracting significant changes with respect to this baseline from single-cell datasets. We find 10 different clusters of B cells and applied a novel, geometry-inspired, method to RNA velocity estimates in order to evaluate the dynamic transitions between B cell clusters. This indicated the presence of two main developmental branches of memory B cells. A T-independent branch that involves IgM memory cells and two DN subpopulations, culminating in a population thought to be associated with Age related B cells and the extrafollicular response. The other, T-dependent, branch involves a third DN cluster which appears to be a precursor of classical memory cells. In addition, we identify a novel DN4 population, which is IgE rich and closely linked to the classical/precursor memory branch suggesting an IgE specific T-dependent cell population.

The term “big data” refers broadly to large volumes of data, often gathered from several sources, that are then analyzed, for example, for predictive analytics. Combining and mining genetic data from varied sources including clinical genetic testing, for example, electronic health records, what might be termed as “recreational” genetic testing such as ancestry testing, as well as research studies, provide one type of “big data.” Challenges and cautions in analyzing big data include recognizing the lack of systematic collection of the source data, the variety of assay technologies used, the potential variation in classification and interpretation of genetic variants. While advanced technologies such as microarrays and, more recently, next-generation sequencing, that enable testing an individual's DNA for thousands of genes and variants simultaneously are briefly discussed, attention is focused more closely on challenges to analysis of the massive data generated by these genomic technologies. The main theme of this review is to evaluate challenges associated with big data in general and specifically to bring the sophisticated technology of genetic/genomic testing down to the individual level, keeping in mind the human aspect of the data source and considering where the impact of the data will be translated and applied. Considerations in this “humanizing” process include providing adequate counseling and consent for genetic testing in all settings, as well as understanding the strengths and limitations of assays and their interpretation.

An understanding of suspended particulate matter (SPM) dynamics is of great importance to design awareness and management strategies of estuaries. Using a Laser In Situ Scattering and Transmissiometry (LISST) instrument, variations in suspended particle size volumetric concentrations (VC) and particle size distributions (PSD) were measured at six sites within Port Curtis estuary (Australia). The port is a macrotidal estuary with significant economic and environmental importance. Observed VC and SPM sizes demonstrated spatial and temporal trends strongly controlled by the variable energy conditions operating on the neap and spring cycle timescale, with a clear trend towards increasing concentrations and decreasing SPM sizes with increasing tidal ranges. Mid-estuary sites were characterized by the greatest depth-averaged VC under transitional and spring conditions. Estuary-wide mean spring tide total water profile concentrations revealed a near 300% increase in comparison to neap tide condition concentrations. In the upper-estuary sites the mean contribution of the combined 2.5–35 µm size classes to the total profile PSDs was greatest during all tidal conditions, whilst within the lower-estuary site the combined 35–130 µm size classes were greatest. Mean contributions of the largest size class (300–500 µm) dominated surface-waters throughout the estuary during the neap tide period, which when compared with the transitional and spring tide conditions, demonstrated changes of −82% to −48% and −82% to −40%, respectively. Overall, the results from this case study provides further evidence of the important influence of neap and spring tidal regimes on SPM dynamics within estuarine settings and the need to observe parameter dynamics on such timescales.

Abstract Pure cellulose nanocrystal (CNC) aerogels with controlled 3D structures and inner pore architecture are printed using the direct ink write (DIW) technique. While traditional cellulosic aerogel processing approaches lack the ability to easily fabricate complete aerogel structures, DIW 3D printing followed by freeze drying can overcome this shortcoming and can produce CNC aerogels with minimal structural shrinkage or damage. The resultant products have great potential in applications such as tissue scaffold templates, drug delivery, packaging, etc., due to their inherent sustainability, biocompatibility, and biodegradability. Various 3D structures are successfully printed without support material, and the print quality can be improved with increasing CNC concentration and printing resolution. Dual pore CNC aerogel scaffolds are also successfully printed, where the customizable 3D structure and inner pore architecture can potentially enable advance CNC scaffold designs suited for specific cell integration requirements.

Obesity is associated with increased risk of breast and other cancers. However, the complexity of the underlying mechanisms, together with the interplay of diet and physical activity—contributing to energy balance—and the role of adipose tissue, pose challenges to our understanding of the basis of this increased risk. Epidemiologic studies have documented a higher obesity prevalence in US black women compared to white women. Elucidation of the contribution of potential biological differences among racially distinct groups to their differences in breast cancer (BC) risk and mortality have been topics of considerable interest in recent years. The racial and ethnic variation in body fat distribution may account for at least part of the differences in breast cancer rates in these populations. Yet, while black women exhibit higher rates of obesity compared to white women, this does not translate directly into higher rates of BC. In fact, overall, BC in black women occurs with a lower incidence than BC in white women. Obesity is a known risk factor for postmenopausal breast cancer, and growing evidence suggests that abdominal obesity, also known as central obesity, may increase risk for triple negative breast cancer, which is more common in premenopausal women. The positive association of postmenopausal BC risk and specifically estrogen receptor (ER)-positive BC, is presumably due largely to accumulation of estrogen in the adipose tissue of the breast and other tissues. Of the two main types of adipose tissue—subcutaneous and visceral—visceral adipocytes are more active metabolically. Such adipose tissue harbors multiple molecular entities that promote carcinogenesis: endocrine molecules/hormones, immunologic factors, inflammatory cytokines, metabolic alterations, and other components of the microenvironment. Expression of these culpable entities is largely regulated by epigenetic mechanisms. The interrelationship between these entities and drivers of epigenetic alteration are critical to the regulation of pathways connecting obesity and cancer risk. Initiatives to counteract the carcinogenic effects of obesity have primarily involved modulation of energy balance by diet. However, targeting of specific molecular abnormalities characterizing adiposity offers an alternative approach to preventing cancer. Our goal in this review is to first discuss the major mechanisms contributing to the obesity-breast cancer link. We will also consider race, specifically black/white differences, as they relate to the association of obesity with breast cancer risk. Then we will enumerate strategies targeting these mechanisms to reduce BC risk, in large part by way of dietary interventions with potential to mitigate the cancer-promoting components of adiposity.

Traumatic brain injury (TBI) is associated with increased risk for psychological and substance use disorders. The study aim is to determine incidence and risk factors for persistent opioid prescription after hospitalization for TBI. Electronic medical records of patients age ≥ 18 admitted to a neuroscience intensive care unit between January 2013 and February 2017 for an intracranial injury were retrospectively reviewed. Primary outcome was opioid use through 12 months post-hospital discharge. A total of 298 patients with complete data were included in the analysis. The prevalence of opioid use among preadmission opioid users was 48 (87%), 36 (69%) and 22 (56%) at 1, 6 and 12-months post-discharge, respectively. In the opioid naïve group, 69 (41%), 24 (23%) and 17 (19%) were prescribed opioids at 1, 6 and 12 months, respectively. Preadmission opioid use (OR 324.8, 95% CI 23.1-16907.5, p = 0.0004) and higher opioid requirements during hospitalization (OR 4.5, 95% CI 1.8-16.3, p = 0.006) were independently associated with an increased risk of being prescribed opioids 12 months post-discharge. These factors may be used to identify and target at-risk patients for intervention.