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Abstract Background Epigenome analysis relies on defined sets of genomic regions output by widely used assays such as ChIP-seq and ATAC-seq. Statistical analysis and visualization of genomic region sets is essential to answer biological questions in gene regulation. As the epigenomics community continues generating data, there will be an increasing need for software tools that can efficiently deal with more abundant and larger genomic region sets. Here, we introduce GenomicDistributions, an R package for fast and easy summarization and visualization of genomic region data. Results GenomicDistributions offers a broad selection of functions to calculate properties of genomic region sets, such as feature distances, genomic partition overlaps, and more. GenomicDistributions functions are meticulously optimized for best-in-class speed and generally outperform comparable functions in existing R packages. GenomicDistributions also offers plotting functions that produce editable ggplot objects. All GenomicDistributions functions follow a uniform naming scheme and can handle either single or multiple region set inputs. Conclusions GenomicDistributions offers a fast and scalable tool for exploratory genomic region set analysis and visualization. GenomicDistributions excels in user-friendliness, flexibility of outputs, breadth of functions, and computational performance. GenomicDistributions is available from Bioconductor ( https://bioconductor.org/packages/release/bioc/html/GenomicDistributions.html ).

Abstract Nascent RNA profiling is growing in popularity; however, there is no standard analysis pipeline to uniformly process the data and assess quality. Here, we introduce PEPPRO, a comprehensive, scalable workflow for GRO-seq, PRO-seq, and ChRO-seq data. PEPPRO produces uniformly processed output files for downstream analysis and assesses adapter abundance, RNA integrity, library complexity, nascent RNA purity, and run-on efficiency. PEPPRO is restartable and fault-tolerant, records copious logs, and provides a web-based project report. PEPPRO can be run locally or using a cluster, providing a portable first step for genomic nascent RNA analysis.

Abstract A key challenge in epigenetics is to determine the biological significance of epigenetic variation among individuals. We present Coordinate Covariation Analysis (COCOA), a computational framework that uses covariation of epigenetic signals across individuals and a database of region sets to annotate epigenetic heterogeneity. COCOA is the first such tool for DNA methylation data and can also analyze any epigenetic signal with genomic coordinates. We demonstrate COCOA’s utility by analyzing DNA methylation, ATAC-seq, and multi-omic data in supervised and unsupervised analyses, showing that COCOA provides new understanding of inter-sample epigenetic variation. COCOA is available on Bioconductor ( http://bioconductor.org/packages/COCOA ).

In motor-related brain regions, movement intention has been successfully decoded from in-vivo spike train by isolating a lower-dimension manifold that the high-dimensional spiking activity is constrained to. The mechanism enforcing this constraint remains unclear, although it has been hypothesized to be implemented by the connectivity of the sampled neurons. We test this idea and explore the interactions between local synaptic connectivity and its ability to encode information in a lower dimensional manifold through simulations of a detailed microcircuit model with realistic sources of noise. We confirm that even in isolation such a model can encode the identity of different stimuli in a lower-dimensional space. We then demonstrate that the reliability of the encoding depends on the connectivity between the sampled neurons by specifically sampling populations whose connectivity maximizes certain topological metrics. Finally, we developed an alternative method for determining stimulus identity from the activity of neurons by combining their spike trains with their recurrent connectivity. We found that this method performs better for sampled groups of neurons that perform worse under the classical approach, predicting the possibility of two separate encoding strategies in a single microcircuit.

In the past decade, defective DNA repair has been increasingly linked with cancer progression. Human tumors with markers of defective DNA repair and increased replication stress exhibit genomic instability and poor survival rates across tumor types. Seminal studies have demonstrated that genomic instability develops following inactivation of BRCA1, BRCA2, or BRCA-related genes. However, it is recognized that many tumors exhibit genomic instability but lack BRCA inactivation. We sought to identify a pan-cancer mechanism that underpins genomic instability and cancer progression in BRCA-wildtype tumors. Methods: Using multi-omics data from two independent consortia, we analyzed data from dozens of tumor types to identify patient cohorts characterized by poor outcomes, genomic instability, and wildtype BRCA genes. We developed several novel metrics to identify the genetic underpinnings of genomic instability in tumors with wildtype BRCA. Associated clinical data was mined to analyze patient responses to standard of care therapies and potential differences in metastatic dissemination. Results: Systematic analysis of the DNA repair landscape revealed that defective single-strand break repair, translesion synthesis, and non-homologous end-joining effectors drive genomic instability in tumors with wildtype BRCA and BRCA-related genes. Importantly, we find that loss of these effectors promotes replication stress, therapy resistance, and increased primary carcinoma to brain metastasis. Conclusions: Our results have defined a new pan-cancer class of tumors characterized by replicative instability (RIN). RIN is defined by the accumulation of intra-chromosomal, gene-level gain and loss events at replication stress sensitive (RSS) genome sites. We find that RIN accelerates cancer progression by driving copy number alterations and transcriptional program rewiring that promote tumor evolution. Clinically, we find that RIN drives therapy resistance and distant metastases across multiple tumor types.

Abstract Background Elucidating the effect of source-sink relations on berry composition is of interest for wine grape production as it represents a mechanistic link between yield, photosynthetic capacity and wine quality. However, the specific effects of carbohydrate supply on berry composition are difficult to study in isolation as leaf area or crop adjustments can also change fruit exposure, or lead to compensatory growth or photosynthetic responses. A new experimental system was therefore devised to slow berry sugar accumulation without changing canopy structure or yield. This consisted of six transparent 1.2 m3 chambers to enclose large pot-grown grapevines, and large soda-lime filled scrubbers that reduced carbon dioxide (CO2) concentration of day-time supply air by approximately 200 ppm below ambient. Results In the first full scale test of the system, the chambers were installed on mature Shiraz grapevines for 14 days from the onset of berry sugar accumulation. Three chambers were run at sub-ambient CO2 for 10 days before returning to ambient. Canopy gas exchange, and juice hexose concentrations were determined. Net CO2 exchange was reduced from 65.2 to 30 g vine− 1 day− 1, or 54%, by the sub-ambient treatment. At the end of the 10 day period, total sugar concentration was reduced from 95 to 77 g L− 1 from an average starting value of 23 g L− 1, representing a 25% reduction. Scaling to a per vine basis, it was estimated that 223 g of berry sugars accumulated under ambient supply compared to 166 g under sub-ambient, an amount equivalent to 50 and 72% of total C assimilated. Conclusions Through supply of sub-ambient CO2 using whole canopy gas exchange chambers system, an effective method was developed for reducing photosynthesis and slowing the rate of berry sugar accumulation without modifying yield or leaf area. While in this case developed for further investigations of grape and wine composition, the system has broader applications for the manipulation and of study of grapevine source-sink relations.

We present a new computing package Flagser, designed to construct the directed flag complex of a finite directed graph, and compute persistent homology for flexibly defined filtrations on the graph and the resulting complex. The persistent homology computation part of Flagser is based on the program Ripser by U. Bauer, but is optimised specifically for large computations. The construction of the directed flag complex is done in a way that allows easy parallelisation by arbitrarily many cores. Flagser also has the option of working with undirected graphs. For homology computations Flagser has an approximate option, which shortens compute time with remarkable accuracy. We demonstrate the power of Flagser by applying it to the construction of the directed flag complex of digital reconstructions of brain microcircuitry by the Blue Brain Project and several other examples. In some instances we perform computation of homology. For a more complete performance analysis, we also apply Flagser to some other data collections. In all cases the hardware used in the computation, the use of memory and the compute time are recorded.

Mammalian α-defensins are a family of abundant effector peptides of the mucosal innate immune system. Although primarily considered to be antimicrobial, α-defensins can increase rather than block infection by certain prominent bacterial and viral pathogens in cell culture and in vivo. We have shown previously that exposure of mouse and human adenoviruses (HAdVs) to α-defensins is able to overcome competitive inhibitors that block cell binding, leading us to hypothesize a defensin-mediated binding mechanism that is independent of known viral receptors. To test this hypothesis, we used genetic approaches to demonstrate that none of several primary receptors nor integrin co-receptors are needed for human α-defensin-mediated binding of HAdV to cells; however, infection remains integrin dependent. Thus, our studies have revealed a novel pathway for HAdV binding to cells that bypasses viral primary receptors. We speculate that this pathway functions in parallel with receptor-mediated entry and contributes to α-defensin-enhanced infection of susceptible cells. Remarkably, we also found that in the presence of α-defensins, HAdV tropism is expanded to non-susceptible cells, even when viruses are exposed to a mixture of both susceptible and non-susceptible cells. Therefore, we propose that in the presence of sufficient concentrations of α-defensins, such as in the lung or gut, integrin expression rather than primary receptor expression will dictate HAdV tropism in vivo. In summary, α-defensins may contribute to tissue tropism not only through the neutralization of susceptible viruses but also by allowing certain defensin-resistant viruses to bind to cells independently of previously described mechanisms.

Abstract Background Early blood transfusion improves survival in patients with life-threatening bleeding, but the optimal transfusion strategy in the pre-hospital setting has yet to be established. Although there is some evidence of benefit with the use of whole blood, there have been no randomised controlled trials exploring the clinical and cost effectiveness of pre-hospital administration of whole blood versus component therapy for trauma patients with life-threatening bleeding. The aim of this trial is to determine whether pre-hospital leukocyte-depleted whole blood transfusion is better than standard care (blood component transfusion) in reducing the proportion of participants who experience death or massive transfusion at 24 h. Methods This is a multi-centre, superiority, open-label, randomised controlled trial with internal pilot and within-trial cost-effectiveness analysis. Patients of any age will be eligible if they have suffered major traumatic haemorrhage and are attended by a participating air ambulance service. The primary outcome is the proportion of participants with traumatic haemorrhage who have died (all-cause mortality) or received massive transfusion in the first 24 h from randomisation. A number of secondary clinical, process, and safety endpoints will be collected and analysed. Cost (provision of whole blood, hospital, health, and wider care resource use) and outcome data will be synthesised to present incremental cost-effectiveness ratios for the trial primary outcome and cost per quality-adjusted life year at 90 days after injury. We plan to recruit 848 participants (a two-sided test with 85% power, 5% type I error, 1-1 allocation, and one interim analysis would require 602 participants—after allowing for 25% of participants in traumatic cardiac arrest and an additional 5% drop out, the sample size is 848). Discussion The SWiFT trial will recruit 848 participants across at least ten air ambulances services in the UK. It will investigate the clinical and cost-effectiveness of whole blood transfusion versus component therapy in the management of patients with life-threatening bleeding in the pre-hospital setting. Trial registration ISRCTN: 23657907; EudraCT: 2021-006876-18; IRAS Number: 300414; REC: 22/SC/0072, 21 Dec 2021.

Abstract Context Patient experience is an important component of high‐quality care and is linked to improved clinical outcomes across a range of different conditions. Patient‐reported experience measures (PREMs) are psychometrically validated instruments designed to identify where strengths and vulnerabilities in care exist. Currently, there is no validated instrument available to measure patient experience among people aged over 65 years attending the emergency department (ED). Objective This paper aims to describe the process of generating, refining and prioritising candidate items for inclusion in a new PREM measuring older adults' experiences in ED (PREM‐ED 65). Design One hundred and thirty‐six draft items were generated via a systematic review, interviews with patients and focus groups with ED staff exploring older adults' experiences in the ED. A 1‐day multiple stakeholder workshop was then convened to refine and prioritise these items. The workshop entailed a modified nominal groups technique exercise comprised of three discrete parts—(i) item familiarisation and comprehension assessment, (ii) initial voting and (iii) final adjudication. Setting and Participants Twenty‐nine participants attended the stakeholder workshop, conducted in a nonhealthcare setting (Buckfast Abbey). The average age of participants was 65.6 years. Self‐reported prior experiences of emergency care among the participants included attending the ED as a patient (n = 16, 55.2%); accompanying person (n = 11, 37.9%) and/or as a healthcare provider (n = 7, 24.1%). Results Participants were allocated time to familiarise themselves with the draft items, suggest any improvements to the item structure or content, and suggest new items. Two additional items were proposed by participants, yielding a total of 138 items for prioritisation. Initial prioritisation deemed most items ‘critically important’ (priority 7–9 out of 9, n = 104, 75.4%). Of these, 70 items demonstrated suitable inter‐rater agreement (mean average deviation from the median

Introduction Pharmacists provide a spectrum of services and comprehensive medication management for patients with substance use disorders (SUDs) with many providing timely and increased access to care for patients. Prior studies have evaluated other healthcare professionals’ attitudes, knowledge and practice in regard to SUD treatment and harm reduction services. However, no reviews to date summarise the available literature on the attitudes, knowledge and practice in regard to SUD treatment and harm reduction services from the pharmacist perspective. This scoping review aims to systematically map the extent, range and nature of available evidence and identify and describe gaps in knowledge, practice and attitudes towards SUD treatment among pharmacists with the goal of providing information for meaningful integration of pharmacists into SUD care.Methods and analysis We will use the framework proposed by Arksey and O’Malley (2005) updated with recommendations by Levac et al (2010) and the Joanna Briggs Institute (2020). The protocol is registered via Open Science Framework (https://osf.io/92dek). We will search for peer-reviewed literature containing empirical evidence investigating SUD treatment or harm reduction with outcomes pertaining to the knowledge, practice or attitudes of pharmacists. Findings will be guided and assessed by research objectives and summarised using descriptive statistics and thematically for quantitative and qualitative findings, respectively. This review will be conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews.Ethics and dissemination Our findings will provide crucial information and support for future interventions and programmes which aim to meaningfully integrate pharmacists into SUD care. We will disseminate findings at conferences and publish in a peer-reviewed journal. In addition, we will integrate feedback on search strategy, data extraction and our dissemination approach from multidisciplinary collaborators including those within our team’s institution and outside experts with clinical or administrative knowledge in SUD care.

ObjectivesTo assess whether different cervical spine immobilisation strategies (full immobilisation, movement minimisation or no immobilisation), impact neurological and/or other outcomes for patients with suspected cervical spinal injury in the pre-hospital and emergency department setting.DesignSystematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesMEDLINE, EMBASE, CINAHL, Cochrane Library and two research registers were searched until September 2023.Eligibility criteriaAll comparative studies (prospective or retrospective) that examined the potential benefits and/or harms of immobilisation practices during pre-hospital and emergency care of patients with a potential cervical spine injury (pre-imaging) following blunt trauma.Data extraction and synthesisTwo authors independently selected and extracted data. Risk of bias was appraised using the Cochrane ROBINS-I tool for non-randomised studies. Data were synthesised without meta-analysis.ResultsSix observational studies met the inclusion criteria. The methodological quality was variable, with most studies having serious or critical risk of bias. The effect of cervical spine immobilisation practices such as full immobilisation or movement minimisation during pre-hospital and emergency care did not show clear evidence of benefit for the prevention of neurological deterioration, spinal injuries and death compared with no immobilisation. However, increased pain, discomfort and anatomical complications were associated with collar application during immobilisation.ConclusionsDespite the limited evidence, weak designs and limited generalisability, the available data suggest that pre-hospital cervical spine immobilisation (full immobilisation or movement minimisation) was of uncertain value due to the lack of demonstrable benefit and may lead to potential complications and adverse outcomes. High-quality randomised comparative studies are required to address this important question.Trial registrationPROSPERO REGISTRATION Fiona Lecky, Abdullah Pandor, Munira Essat, Anthea Sutton, Carl Marincowitz, Gordon Fuller, Stuart Reid, Jason Smith. A systematic review of cervical spine immobilisation following blunt trauma in pre-hospital and emergency care. PROSPERO 2022 CRD42022349600 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022349600.

The distinction between weak and strong islands has been extensively explored in the literature from both a descriptive and analytical perspective. In this paper, I document and analyze island constructions and constraints in Mende, an understudied Mande language spoken in Sierra Leone. Mende has both weak islands (left branch and wh-islands) and strong islands (adjunct clauses, sentential subjects, and coordinate structures). Intriguingly, it has a third class of islands, that I call mixed islands which show a subject–non-subject asymmetry in allowing for movement out of relative clauses, only when they modify the subject. As such, subject-modifying RCs cannot be classified as (strong/weak) islands in Mende. This is the first systematic work on islands and island constraints in the Mande language family, and, as such, it brings novel data from an understudied language family to bear on our understanding of A-bar dependencies and the study of island escape in African languages. It also calls into question a neat paradigm of cross-linguistic island constraints. Importantly, this work also lays down a baseline for future research on island constraints in the broader Mande language family. In order to discuss island constraints, this paper also lays out the first analysis of relative clauses in Mende, while integrating new research on the left periphery, focus constructions, and wh-constructions.

Antivirals with broad coronavirus activity are important for treating high-risk individuals exposed to the constantly evolving SARS-CoV-2 variants of concern (VOCs) as well as emerging drug-resistant variants. We developed and characterized a novel class of active-site-directed 3-chymotrypsin-like protease (3CLpro) inhibitors (C2–C5a). Our lead direct-acting antiviral (DAA), C5a, is a non-covalent, non-peptide with a dissociation constant of 170 nM against recombinant SARS-CoV-2 3CLpro. The compounds C2–C5a exhibit broad-spectrum activity against Omicron subvariants (BA.5, BQ.1.1, and XBB.1.5) and seasonal human coronavirus-229E infection in human cells. Notably, C5a has median effective concentrations of 30–50 nM against BQ.1.1 and XBB.1.5 in two different human cell lines. X-ray crystallography has confirmed the unique binding modes of C2–C5a to the 3CLpro, which can limit virus cross-resistance to emerging Paxlovid-resistant variants. We tested the effect of C5a with two of our newly discovered host-directed antivirals (HDAs): N-0385, a TMPRSS2 inhibitor, and bafilomycin D (BafD), a human vacuolar H+-ATPase [V-ATPase] inhibitor. We demonstrated a synergistic action of C5a in combination with N-0385 and BafD against Omicron BA.5 infection in human Calu-3 lung cells. Our findings underscore that a SARS-CoV-2 multi-targeted treatment for circulating Omicron subvariants based on DAAs (C5a) and HDAs (N-0385 or BafD) can lead to therapeutic benefits by enhancing treatment efficacy. Furthermore, the high-resolution structures of SARS-CoV-2 3CLpro in complex with C2–C5a will facilitate future rational optimization of our novel broad-spectrum active-site-directed 3C-like protease inhibitors.

Obesity produces a systemic low-grade inflammation associated with many adverse health conditions and, as we recently learned, with complications of COVID-19. Functional studies in animal models have demonstrated that asperuloside, an iridoid glycoside found in many medicinal plants, has produced promising anti-obesity results. However, the safety profile and the anti-inflammatory properties of asperuloside remain unknown. Here, we confirmed the previously reported anti-obesity properties of asperuloside, and, importantly, we performed toxicity studies assessing cell viability providing a dose reference for future animal experiments. Asperuloside significantly reduced blood levels of leptin and the mRNA levels of orexigenic peptides, such as NPY and AgRP in mice consuming HFD, with no effect on mice eating a standard chow diet. In addition, our results indicate that ASP reduced both hypothalamic and hepatic mRNA levels of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α as well as the blood levels of plasminogen activator inhibitor-1 (PAI-1), which are known to play a major role in the development of insulin resistance and cardiovascular complications. Collectively, our findings suggest that asperuloside is a safe compound for long-term use in animal models and that it reduces the elevated levels of pro-inflammatory cytokines occurring in obesity.

Background: Topical lidocaine patches, applied over rib fractures, have been suggested as a non-invasive method of local anaesthetic delivery to improve respiratory function, reduce opioid consumption and consequently reduce pulmonary complications. Older patients may gain most benefit from improved analgesic regimens yet lidocaine patches are untested as an early intervention in the Emergency Department (ED). The aim of this trial is to investigate uncertainties around trial design and conduct, to establish whether a definitive randomised trial of topical lidocaine patches in older patients with rib fractures is feasible. Methods: RELIEF is an open label, multicentre, parallel group, individually randomised, feasibility randomised controlled trial with economic scoping and nested qualitative study. Patients aged ≥ 65 years presenting to the ED with traumatic rib fracture(s) requiring admission will be randomised 1:1 to lidocaine patches (intervention), in addition to standard clinical management, or standard clinical management alone. Lidocaine patches will be applied immediately after diagnosis in ED and continued daily for 72 hours or until discharge. Feasibility outcomes will focus on recruitment, adherence and follow-up data with a total sample size of 100. Clinical outcomes, such as 30-day pulmonary complications, and resource use will be collected to understand feasibility of data collection. Qualitative interviews will explore details of the trial design, trial acceptability and recruitment processes. An evaluation of the feasibility of measuring health economics outcomes data will be completed. Discussion: Interventions to improve outcomes in elderly patients with rib fractures are urgently required. This feasibility trial will test a novel early intervention which has the potential of fulfilling this unmet need. The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF) feasibility trial will determine whether a definitive trial is feasible. ISRCTN Registration: ISRCTN14813929 (22/04/2021).

In the late fall of 2018, foliar rust (referred to as ironwood/hophornbeam leaf rust [IHLR]) was discovered in several counties in Florida, United States, on ironwood (Carpinus caroliniana) and hophornbeam (Ostrya virginiana), both members of the Betulaceae. Uredinia were observed on leaves and, in some cases, samaras of both species at numerous locations on trees of all age classes. Similar reports across the southeastern United States (Georgia, the Carolinas, Tennessee, and Texas) were detected the following year, with European hornbeam (Carpinus betulus) being reported as an additional host, while Ostrya virginiana var. guatemalensis in El Salvador was also discovered showing signs of uredinial infection. Field observations and analyses of morphological data obtained with light and scanning electron microscopy on IHLR and related Melampsoridium herbarium samples and combined molecular data from the ITS and LSU loci indicate that (i) IHLR across samples from the southeastern United States and El Salvador belong to the same taxon; (ii) IHLR is closely affiliated to M. asiaticum; and (iii) some taxonomic modifications might be necessary at the genus level. No alternative (gametophyte) host has been identified, and the rust is likely overwintering in the uredinial stage. This disease represents a novel leaf pathogen on these hosts in North America, and efforts are needed to monitor future disease epidemiology and impacts on these native and cultivated tree species.

Objectives Our understanding of blunt cerebrovascular injury (BCVI) has changed significantly in recent decades, resulting in a heterogeneous description of diagnosis, treatment, and outcomes in the literature which is not suitable for data pooling. Therefore, we endeavored to develop a core outcome set (COS) to help guide future BCVI research and overcome the challenge of heterogeneous outcomes reporting.Methods After a review of landmark BCVI publications, content experts were invited to participate in a modified Delphi study. For round 1, participants submitted a list of proposed core outcomes. In subsequent rounds, panelists used a 9-point Likert scale to score the proposed outcomes for importance. Core outcomes consensus was defined as >70% of scores receiving 7 to 9 and

Förster resonance energy transfer (FRET) microscopy is used in numerous biophysical and biomedical applications to monitor inter- and intramolecular interactions and conformational changes in the 2–10 nm range. FRET is currently being extended to in vivo optical imaging, its main application being in quantifying drug-target engagement or drug release in animal models of cancer using organic dye or nanoparticle-labeled probes. Herein, we compared FRET quantification using intensity-based FRET (sensitized emission FRET analysis with the three-cube approach using an IVIS imager) and macroscopic fluorescence lifetime (MFLI) FRET using a custom system using a time-gated-intensified charge-coupled device, for small animal optical in vivo imaging. The analytical expressions and experimental protocols required to quantify the product fDE of the FRET efficiency E and the fraction of donor molecules involved in FRET, fD, are described in detail for both methodologies. Dynamic in vivo FRET quantification of transferrin receptor-transferrin binding was acquired in live intact nude mice upon intravenous injection of a near-infrared-labeled transferrin FRET pair and benchmarked against in vitro FRET using hybridized oligonucleotides. Even though both in vivo imaging techniques provided similar dynamic trends for receptor-ligand engagement, we demonstrate that MFLI-FRET has significant advantages. Whereas the sensitized emission FRET approach using the IVIS imager required nine measurements (six of which are used for calibration) acquired from three mice, MFLI-FRET needed only one measurement collected from a single mouse, although a control mouse might be needed in a more general situation. Based on our study, MFLI therefore represents the method of choice for longitudinal preclinical FRET studies such as that of targeted drug delivery in intact, live mice.

Ecosystem alterations to Lake Michigan (LM), such as the invasion of dreissenid mussels, have decreased the abundance of phytoplankton and, subsequently, zooplankton, which has implications for Great Lake fisheries. The community composition of zooplankton has also been altered over the past 20 years in LM, shifting the summer dominance from cladoceran to calanoid taxa. However, most of our information on zooplankton community dynamics is from deeper pelagic zones. The nearshore beach (≤1 m) habitat, which serves as a critical nursery for some larvae and juvenile fish, is composed of different zooplankton taxa than deeper zones, but limited data are available for comparison. We conducted a standardized summer sampling campaign to characterize the zooplankton community across 32 beaches in LM. We found the lowest crustacean zooplankton density and biomass on northern LM beaches and a higher zooplankton density and biomass on Greater Green Bay and central LM beaches, which had warmer water temperatures. Smaller-bodied cladocera (mainly Bosmina) and cyclopoid taxa were the most abundant groups on beaches. Our results provide the first comprehensive characterization of zooplankton on beaches in the Great Lakes, with applications for other lake systems. These results may help identify potential “hot spots” of fish recruitment for management.

Post-harvest Salmonella mitigation techniques are insufficient at addressing Salmonella harbored in cattle lymph nodes, necessitating the exploration of pre-harvest alternatives that reduce Salmonella prior to dissemination to the lymph nodes. A 2 × 2, unbalanced experiment was conducted to determine the effectiveness of pre-harvest treatments applied to the pen surface for Salmonella mitigation in cattle. Treatments included manure slurry intended to mimic pen run-off water (n = 4 pens), a bacteriophage cocktail (n = 4), a combination of both treatments (n = 5), and a control group (n = 5) that received no treatment. Environment samples from 18 feedlot pens and fecal grabs, hide swabs, and subiliac lymph nodes from 178 cattle were collected and selectively enriched for Salmonella, and Salmonella isolates were sequenced. The combination treatment was most effective at reducing Salmonella, and the prevalence was significantly lower compared with the control group for rump swabs on Days 14 and 21. The treatment impact on Salmonella in the lymph nodes could not be determined due to low prevalence. The reduction on cattle hides suggests that bacteriophage or water treatments applied to the feedlot pen surface may reduce Salmonella populations in cattle during the pre-harvest period, resulting in reduced contamination during slaughter and processing.

Tobacco smoking imposes a staggering burden on public health, underscoring the urgency of developing a deeper understanding of the processes that maintain addiction. Clinical and experience-sampling data highlight the importance of anxious withdrawal symptoms, but the underlying neurobiology has remained elusive. Mechanistic work in animals implicates the central extended amygdala (EAc)-including the central nucleus of the amygdala and the neighboring bed nucleus of the stria terminalis-but the translational relevance of these discoveries remains unexplored. Here we leveraged a randomized trial design, well-established threat-anticipation paradigm, and multidimensional battery of assessments to understand the consequences of 24-hour nicotine abstinence. The threat-anticipation paradigm had the expected consequences, amplifying subjective distress and arousal, and recruiting the canonical threat-anticipation network. Abstinence increased smoking urges and withdrawal symptoms, and potentiated threat-evoked distress, but had negligible consequences for EAc threat reactivity, raising questions about the translational relevance of prominent animal and human models of addiction. These observations provide a framework for conceptualizing nicotine abstinence and withdrawal, with implications for basic, translational, and clinical science.

Abstract Introduction Cognitive training can potentially reduce risk of cognitive decline and dementia in older adults. To support implementation of cognitive training in the broader population of older adults, it is critical to evaluate intervention implementation and efficacy among representative samples, particularly those at highest risk of cognitive decline. Hearing and vision impairments are highly prevalent among older adults and confer increased risk of cognitive decline/dementia. Whether cognitive training interventions enroll and are designed to include this important subgroup is unknown. Methods A scoping review of PubMed and PsycINFO was conducted to examine the inclusion of older adults with hearing and vision impairment in cognitive training interventions. Two independent reviewers completed a full‐text review of eligible articles. Eligible articles included cognitive training and multimodal randomized controlled trials and a study population that was cognitively unimpaired, aged ≥55‐years, and community dwelling. Articles were primary outcome papers published in English. Results Among the 130 articles included in the review, 103 were cognitive training interventions (79%) and 27 were multimodal interventions (21%). More than half the trials systematically excluded participants with hearing and/or vision impairment (n = 60, 58%). Few studies reported hearing and vision measurement (cognitive: n = 16, 16%; multimodal: n = 3, 11%) or incorporated universal design and accessibility into intervention design (cognitive: n = 7, 7%; multimodal: n = 0, 0%). Discussion Older adults with hearing and vision impairment are underrepresented in cognitive training interventions. Reporting of hearing and vision measurement, proper justification of exclusions, and inclusion of accessibility and universal intervention design are also lacking. These findings raise concerns about whether current trial findings apply to those with hearing and vision impairment and generalize to the broader population of older adults. It is critical to include more diverse study populations and integrate accessibility into intervention design to include and better represent older adults with hearing and vision impairment. Highlights Cognitive training interventions underrepresent hearing and vision impairment. Sensory measurement and proper justification of exclusions are rarely reported. Interventions lack inclusion of accessibility and universal intervention design. More diverse study populations are needed in cognitive training interventions. Integration of accessibility into cognitive training intervention design is needed

Background: Acute brain death (ABD) is associated with inflammation and lung injury. Direct peritoneal resuscitation (DPR) improves blood flow to the vital organs after ABD. DPR reduces lung injury, but the mechanism for this is unknown. Methods: Male Sprague-Dawley rats were randomized to five groups (n = 8/group): (1) Sham (no ABD); (2) Targeted intravenous fluid (TIVF) (ABD plus enough IVF to maintain a MAP of 80 mmHg) at 2 hours post-resuscitation (RES); (3) ABD + TIVF + DPR (TIVF and 30 cc intraperitoneal 2.5% Delflex) at 2 hours post-RES; (4) ABD + TIVF at 4 hours post-RES; and (5) ABD + TIVF + DPR at 4 hours post-RES. Messenger RNA (mRNA) levels were measured using Qiagen qRT PCR. Protein levels were assessed using quantitative ELISAs and the Luminex MagPix system. Results: Use of DPR caused 5.8-fold downregulation of mRNA expression for TNF-α and 2.7-fold decrease for the TNF receptor compared to TIVF alone. Caspase 8 mRNA was also downregulated. Protein levels for TNF-α, TNF receptor, caspase 8, NFκB, and NFκB inhibitor kinase, which promotes dissociation of NFκB inhibitor, were reduced by DPR. Cell death markers M30 and M65 were also decreased with DPR. Conclusions: Use of DPR caused changes in the expression of multiple mRNAs and proteins in the caspase 8 apoptotic pathway. These data represent a mechanism through which DPR exerts its beneficial effects within the lung tissue.

Species in the Laetiporus sulphureus species complex, also known as “chicken of the woods” mushrooms, are wood-decay fungi that cause brown rot within the heartwood of their tree hosts. The common name “chicken of the woods” is given to some species in this group because they are tasty edible mushrooms. Several Laetiporus species have been harvested to use as food colorants, to dye natural products such as wool, and for human consumption. This new 4-page publication of the UF/IFAS Plant Pathology Department, written by Brianna Benitez, Claudia A. Paez, Matthew E. Smith, and Jason A. Smith, describes these fungi as well as their ecology, management, and potential edibility. https://edis.ifas.ufl.edu/pp358

The poset P of all permutations ordered by pattern containment is a fundamental object of study in the field of permutation patterns. This poset has a very rich and complex topology and an understanding of its Möbius function has proved particularly elusive, although results have been slowly emerging in the last few years. Using a variety of topological techniques we present a two term formula for the Mo ̈bius function of intervals in P. The first term in this formula is, up to sign, the number of so called normal occurrences of one permutation in another. Our definition of normal occurrences is similar to those that have appeared in several variations in the literature on the Möbius function of this and other posets, but simpler than most of them. The second term in the formula is (still) complicated, but we conjecture that it equals zero for a significant proportion of intervals. We present some cases where the second term vanishes and others where it is nonzero. Computing the Möbius function recursively from its definition has exponential complexity, whereas the computation of the first term in our formula is polynomial and the exponential part is isolated to the second term, which seems to often vanish. This is thus the first polynomial time formula for the Möbius function of what appears to be a large proportion of all intervals of P.

Biscogniauxia canker or dieback (formerly called Hypoxylon canker or dieback) is a common contributor to poor health and decay in a wide range of tree species (Balbalian & Henn 2014). This disease is caused by several species of fungi in the genus Biscogniauxia (formerly Hypoxylon). B. atropunctata or B. mediterranea are usually the species found on Quercus spp. and other hosts in Florida, affecting trees growing in many different habitats, such as forests, parks, green spaces and urban areas (McBride & Appel, 2009). Typically, species of Biscogniauxia are opportunistic pathogens that do not affect healthy and vigorous trees; some species are more virulent than others. However, once they infect trees under stress (water stress, root disease, soil compaction, construction damage etc.) they can quickly colonize the host. Once a tree is infected and fruiting structures of the fungus are evident, the tree is not likely to survive especially if the infection is in the tree's trunk (Anderson et al., 1995).

Ganoderma Karst. is a large and diverse genus of wood decay fungi that can rot the roots and/or lower trunk of many tree species. There are several laccate (varnished or polished) Ganoderma species that are found in the southeastern United States and this six-page fact sheet provides an overview of the different species. Written by Andrew L. Loyd, Jason A. Smith, Brantlee S. Richter, Robert A. Blanchette, and Matthew E. Smith and published by the Plant Pathology Department.­http://edis.ifas.ufl.edu/pp333

This 6-page fact sheet describes the emergence of these two pathogens of oak and grapevine in North America and Florida; the signs and symptoms of infection; mechanism of host disease and death; fungal morphology; origin, host range, and classification; and management options. Written by Sonja Mullerin and Jason A. Smith, and published by the UF Department of School of Forest Resources and Conservation, March 2015. (Photo: Jason Smith, UF/IFAS)

Armillaria root rot is a disease that decays the root system of many common trees and shrubs. It is caused by several species of Armillaria, fungi that can be recognized by the clusters of yellow to honey-colored mushrooms that emerge during moist conditions. The disease is often lethal, and infected trees may have wilting branches, branch dieback, and stunted growth. Infected trees and shrubs should be removed and replaced with resistant species. This 4-page fact sheet was written by Laura Sanagorski, Aaron Trulock, and Jason Smith, and published by the UF Department of Environmental Horticulture, July 2013. http://edis.ifas.ufl.edu/ep478

Thousand cankers disease of walnut is a tree disease of the edible nut-producing and ornamental tree, black walnut. The first diseased trees were observed in New Mexico in the 1990s. The disease has since spread to most of the western states. Until 2009, diseased black walnut trees were only found outside of the natural range of black walnut, which occurs from the mid-Atlantic states to just west of the Mississippi River. In 2009, it was found near Knoxville, Tennessee; it has since spread to Pennsylvania and Virginia. It is possible that within the next decade this disease could naturally spread to Florida. However, if people continue to move TCD infested walnut logs from place to place, this disease could arrive in Florida tomorrow. This 3-page fact sheet was written by Don Spence and Jason A. Smith, and published by the UF Department of School of Forest Resources and Conservation, February 2013. http://edis.ifas.ufl.edu/fr376