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Abstract The popularity of the term polycrisis suggests a growing demand for new thinking about the world's intersecting crises, but loose and haphazard uses of the concept impede knowledge generation. The special issue, ‘Polycrisis in the Anthropocene’, aims to close the gap. This introductory comment first elaborates upon three key contributions of the lead article ‘Global Polycrisis: The Causal mechanisms of Crisis Entanglement’: a conceptualization of crisis as systemic disequilibrium; the distinction between the slow-moving stresses and the fast-moving trigger events that interact to generate a crisis; and a grammar with which to map the causality of crisis interactions. The commentary then explores three key debates around the polycrisis concept: Are we in a polycrisis, at risk of a polycrisis, or neither? Is the present polycrisis truly unique and unprecedented? And where are power and agency in a systemic approach to polycrisis? These ongoing debates suggest promising directions for polycrisis research that could feature in this special issue and advance the field of polycrisis analysis. Non-technical summary This commentary introduces the special issue ‘Polycrisis in the Anthropocene’ by elaborating upon three major contributions of its lead article, ‘Global Polycrisis: The Causal Mechanisms of Crisis Entanglement’, and exploring three key debates surrounding the polycrisis concept. It invites others to contribute to the special issue in order to advance polycrisis analysis, build a community of knowledge and practice, and generate new insights and strategies with which to address the world's worsening crises. Technical summary The popularity of the term polycrisis suggests a growing demand for new thinking about the world's intersecting crises, but loose and haphazard uses of the concept impede knowledge generation. The special issue, ‘Polycrisis in the Anthropocene’, aims to close the gap. This introductory comment first elaborates upon three key contributions of the lead article ‘Global Polycrisis: The Causal mechanisms of Crisis Entanglement’: a conceptualization of crisis as systemic disequilibrium; the distinction between the slow-moving stresses and the fast-moving trigger events that interact to generate a crisis; and a grammar with which to map the causality of crisis interactions. The commentary then explores three key debates around the polycrisis concept: Are we in a polycrisis, at risk of a polycrisis, or neither? Is the present polycrisis truly unique and unprecedented? And where are power and agency in a systemic approach to polycrisis? These ongoing debates suggest promising directions for polycrisis research that could feature in this special issue and advance the field of polycrisis analysis. Social media summary Inviting contributions and debates to Global Sustainability journal's special issue ‘Polycrisis in the Anthropocene’.

Vascular endothelial cells are exposed to mechanical forces due to their presence at the interface between the vessel wall and flowing blood. The patterns of these mechanical forces (laminar vs. turbulent) regulate endothelial cell function and play an important role in determining endothelial phenotype and ultimately cardiovascular health. One of the key transcriptional mediators of the positive effects of laminar flow patterns on endothelial cell phenotype is the zinc-finger transcription factor, krüppel-like factor 2 (KLF2). Given its importance in maintaining a healthy endothelium, we sought to identify endothelial regulators of the KLF2 transcriptional program as potential new therapeutic approaches to treating cardiovascular disease. Using an approach that utilized both bioinformatics and targeted gene knockdown, we identified endothelial GPCRs capable of modulating KLF2 expression. Genetic screening using siRNAs directed to these GPCRs identified 12 potential GPCR targets that could modulate the KLF2 program, including a subset capable of regulating flow-induced KLF2 expression in primary endothelial cells. Among these targets, we describe the ability of several GPCRs (GPR116, SSTR3, GPR101, LGR4) to affect KLF2 transcriptional activation. We also identify these targets as potential validated targets for the development of novel treatments targeting the endothelium. Finally, we highlight the initiation of drug discovery efforts for LGR4 and report the identification of the first known synthetic ligands to this receptor as a proof-of-concept for pathway-directed phenotypic screening to identify novel drug targets.

IntroductionImproved understanding of the relationship between post-stroke rehabilitation interventions and functional motor outcomes could result in improvements in the efficacy of post-stroke physical rehabilitation. The laterality of motor cortex activity (M1-LAT) during paretic upper-extremity movement has been documented as a useful biomarker of post-stroke motor recovery. However, the expensive, labor intensive, and laboratory-based equipment required to take measurements of M1-LAT limit its potential clinical utility in improving post-stroke physical rehabilitation. The present study tested the ability of a mobile functional near-infrared spectroscopy (fNIRS) system (designed to enable independent measurement by stroke survivors) to measure cerebral hemodynamics at the motor cortex in the homes of chronic stroke survivors.MethodsEleven chronic stroke survivors, ranging widely in their level of upper-extremity motor deficit, used their stroke-affected upper-extremity to perform a simple unilateral movement protocol in their homes while a wireless prototype fNIRS headband took measurements at the motor cortex. Measures of participants' upper-extremity impairment and function were taken.ResultsParticipants demonstrated either a typically lateralized response, with an increase in contralateral relative oxyhemoglobin (ΔHbO), or response showing a bilateral pattern of increase in ΔHbO during the motor task. During the simple unilateral task, M1-LAT correlated significantly with measures of both upper-extremity impairment and function, indicating that participants with more severe motor deficits had more a more atypical (i.e., bilateral) pattern of lateralization.DiscussionThese results indicate it is feasible to gain M1-LAT measures from stroke survivors in their homes using fNIRS. These findings represent a preliminary step toward the goals of using ergonomic functional neuroimaging to improve post-stroke rehabilitative care, via the capture of neural biomarkers of post-stroke motor recovery, and/or via use as part of an accessible rehabilitation brain-computer-interface.

Abstract Drug‐resistant focal epilepsy with regional neocortical seizure onsets originating from the posterior quadrant can be particularly difficult to treat with resective surgery due to the overlap with eloquent cortex. Published reports indicate that corticothalamic treatment targeting the anterior or centromedian nucleus of the thalamus with direct brain‐responsive stimulation may be an effective approach to treat regional neocortical epilepsy. The pulvinar has remained largely unstudied as a neurostimulation target to treat refractory epilepsy. Because the pulvinar has connections with the posterior quadrant, neurostimulation may be effective if applied to seizures originating in this area. We performed a retrospective chart review of patients with regional neocortical seizure onsets in the posterior quadrant treated with the RNS System. Demographics, epilepsy history, clinical seizure frequencies, and neuropsychological testing results were obtained from the chart. Electrocorticogram (ECoG) records stored by the RNS System were reviewed to evaluate electrographic seizure onset patterns. Our patients were followed for 10, 12.5, and 15 months. All patients were responders (≥50% seizure reduction), and two of the three patients experienced a ≥90% reduction in seizures at the last follow‐up. Pre‐ and postsurgical neuropsychological evaluations were compared for two of the patients, and there was no evidence of cognitive decline found in either patient. Interestingly, mild cognitive improvements were reported. The third patient had only postimplant neuropsychological testing data available. Findings for this patient suggested executive dysfunction that was present prior to the RNS System which did not worsen with surgery. A visual inspection of ECoGs revealed near‐simultaneous seizure onsets in neocortical and pulvinar leads in two patients. Seizure onsets in the third patient were more variable. This is the first published report of brain‐responsive neurostimulation targeting the pulvinar to treat refractory regional onset epilepsy of posterior quadrant origin.

Abstract The immunosuppressive regimen for clinical allogeneic islet transplantation uses beta cell–toxic compounds such as tacrolimus that cause islet graft loss. Previously we reported that the plant-derived steroidal lactone Withaferin A (WA) can protect islet grafts by inhibiting nuclear factor-kappa B (NF-κB). Since the NF-κB signaling pathway is essential for T-cell activation, we hypothesized that long-term WA administration may also provide an immunosuppressive effect. Treatment of BALB/c donor islets and C57BL/6N recipients with WA alone resulted in 80% islet graft long-term survival vs. 40% in low-dose FK506-treated mice. In vitro, WA significantly blocked mouse and human T-cell proliferation by CD3/CD28 bead stimulation and in mixed lymphocyte reaction assay. Treatment of immature dendritic cells with WA prevented their maturation in response to inflammatory stimuli, as seen by decreased expression of CD83 and human leukocyte antigen–DR isotype. Exosomes released by islets treated with WA contained significantly fewer proinflammatory molecules interleukin-6, interleukin-8, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, inducible nitric oxide synthase, and cyclooxygenase-2. In conclusion, WA treatment not only reduced inflammation but also prolonged allograft survival, possibly through suppression of dendritic cell maturation and T-cell proliferation. WA has the potential to inhibit both the innate and adaptive immune response to prolong allograft survival.

This study's purpose is to characterize the performance of a prototype functional near-infrared spectroscopy (fNIRS) headband meant to enable quick and easy measurements from the sensorimotor cortices. The fact that fNIRS is well-suited to ergonomic designs (i.e., their ability to be made wireless, their relative robustness to movement artifacts among other characteristics) has resulted in many recent examples of novel ergonomic fNIRS systems; however, the optical nature of fNIRS measurement presents an inherent challenge to measurement at areas of the brain underlying haired parts of the head. It is for this reason that the majority of ergonomic fNIRS systems that have been developed to date target the prefrontal cortex. In the present study we compared the performance of a novel, portable fNIRS headband compared with a stationary full headcap fNIRS system to measure sensorimotor activity during simple upper- and lower-extremity tasks, in healthy individuals >50 years of age. Both fNIRS systems demonstrated the expected pattern of hemodynamic activity in both upper- and lower-extremity tasks, and a comparison of the contrast-to-noise ratio between the two systems suggests the prototype fNIRS headband is non-inferior to a full head cap fNIRS system regarding the ability to detect a physiological response at the sensorimotor cortex during these tasks. These results suggest the use of a wireless and fibreless fNIRS design is feasible for measurement at the sensorimotor cortex.

Sixty years of research on chimpanzees (Pan troglodytes) at Gombe National Park, Tanzania have revealed many similarities with human behaviour, including hunting, tool use and coalitionary killing. The close phylogenetic relationship between chimpanzees and humans suggests that these traits were present in the last common ancestor of Pan and Homo (LCAPH). However, findings emerging from studies of our other closest living relative, the bonobo (Pan paniscus), indicate that either bonobos are derived in these respects, or the many similarities between chimpanzees and humans evolved convergently. In either case, field studies provide opportunities to test hypotheses for how and why our lineage has followed its peculiar path through the adaptive landscape. Evidence from primate field studies suggests that the hominin path depends on our heritage as apes: inefficient quadrupeds with grasping hands, orthograde posture and digestive systems that require high-quality foods. Key steps along this path include: (a) changes in diet; (b) increased use of tools; (c) bipedal gait; (d) multilevel societies; (e) collective foraging, including a sexual division of labour and extensive food transfers; and (f) language. Here I consider some possible explanations for these transitions, with an emphasis on contributions from Gombe.

Total pancreatectomy with islet autotransplantation (TPIAT) is a promising treatment for refractory chronic pancreatitis (CP). Pathological features of CP include progressive fibrosis in pancreas parenchyma, atrophy, and/or ductal occlusion. Complete acinar atrophy (CAA) caused by chronic fibrosis and necroinflammation results in exocrine sufficiency and may influence islet isolation characteristics during TPIAT. In this analysis of patients who underwent TPIAT at our center, we compared transplant outcomes among those with CAA ( n = 5) vs non-acinar atrophy (NAA; matching controls, n = 36). Data were analyzed using one-way analysis of variance with Bonferroni post hoc test or Student’s t test. Pancreas digestion was longer in CAA than in NAA cases (18.6 vs 14.6 min) despite a lower pancreas weight (55.2 vs 91.2 g). Obtained tissue volume was 1.0 ml in the CAA group and 12.1 ml in the NAA group. Both groups had similar islet viability (96%) and islet dose (CAA, 3,391 IEQ/kg; NAA, 4141.1 IEQ/kg). During islet infusion, serum cytokine (IL-6, IL-8, and MCP-1) levels and plasma hsa-miR-375 levels were lower in the CAA group than in the NAA group, but not significantly. Serum tumor necrosis factor α levels at 3 h after infusion were significantly higher in CAA group than in NAA group. After TPIAT, the metabolic outcomes of the CAA group were comparable with that of the NAA group. Narcotics usage decreased significantly over 24 months in both groups, with the CAA group reporting being pain free at 12 months. Complete atrophy of acinar cells of pancreas did not significantly impact islet yield or endocrine function after TPIAT.

Abstract Bioconductor is a widely used R-based platform for genomics, but its host of complex genomic data structures places a cognitive burden on the user. For most tasks, the GRanges object would suffice, but there are gaps in the API that prevent its general use. By recognizing that the GRanges class follows “tidy” data principles, we create a grammar of genomic data transformation, defining verbs for performing actions on and between genomic interval data and providing a way of performing common data analysis tasks through a coherent interface to existing Bioconductor infrastructure. We implement this grammar as a Bioconductor/R package called plyranges.

Science depends on collaboration, result reproduction, and the development of supporting software tools. Each of these requires careful management of software versions. We present a unified model for installing, managing, and publishing software contexts in R. It introduces the package manifest as a central data structure for representing versionspecific, decentralized package cohorts. The manifest points to package sources on arbitrary hosts and in various forms, including tarballs and directories under version control. We provide a high-level interface for creating and switching between side-by-side package libraries derived from manifests. Finally, we extend package installation to support the retrieval of exact package versions as indicated by manifests, and to maintain provenance for installed packages. The provenance information enables the user to publish libraries or sessions as manifests, hence completing the loop between publication and deployment. We have implemented this model across three software packages, switchr, switchrGist and GRANBase, and have released the source code under the Artistic 2.0 license.

Abstract Background Genome editing technologies developed around the CRISPR-Cas9 nuclease system have facilitated the investigation of a broad range of biological questions. These nucleases also hold tremendous promise for treating a variety of genetic disorders. In the context of their therapeutic application, it is important to identify the spectrum of genomic sequences that are cleaved by a candidate nuclease when programmed with a particular guide RNA, as well as the cleavage efficiency of these sites. Powerful new experimental approaches, such as GUIDE-seq, facilitate the sensitive, unbiased genome-wide detection of nuclease cleavage sites within the genome. Flexible bioinformatics analysis tools for processing GUIDE-seq data are needed. Results Here, we describe an open source, open development software suite, GUIDEseq, for GUIDE-seq data analysis and annotation as a Bioconductor package in R. The GUIDEseq package provides a flexible platform with more than 60 adjustable parameters for the analysis of datasets associated with custom nuclease applications. These parameters allow data analysis to be tailored to different nuclease platforms with different length and complexity in their guide and PAM recognition sequences or their DNA cleavage position. They also enable users to customize sequence aggregation criteria, and vary peak calling thresholds that can influence the number of potential off-target sites recovered. GUIDEseq also annotates potential off-target sites that overlap with genes based on genome annotation information, as these may be the most important off-target sites for further characterization. In addition, GUIDEseq enables the comparison and visualization of off-target site overlap between different datasets for a rapid comparison of different nuclease configurations or experimental conditions. For each identified off-target, the GUIDEseq package outputs mapped GUIDE-Seq read count as well as cleavage score from a user specified off-target cleavage score prediction algorithm permitting the identification of genomic sequences with unexpected cleavage activity. Conclusion The GUIDEseq package enables analysis of GUIDE-data from various nuclease platforms for any species with a defined genomic sequence. This software package has been used successfully to analyze several GUIDE-seq datasets. The software, source code and documentation are freely available at http://www.bioconductor.org/packages/release/bioc/html/GUIDEseq.html .

Background: There are few validated tools to measure stigma, particularly among children living with HIV and their families. Methods: This study was nested within a larger study that followed 240 child–caregiver dyads (children aged 10-15 years) at 8 clinics in western Kenya. The stigma instrument was administered to all child–caregiver dyads at 2 time points 6 months apart. The primary end point was to construct validity assessed by comparison to criterion constructs using generalized estimating equation models. Results: Mean age of child participants was 12.3 years and 52% were female. Generally, caregivers reported experiencing higher levels of HIV stigma compared to their children. Children (9%) and caregivers (14%) reported that HIV stigma made them feel stressed, anxious, and depressed. Child and caregiver stigma items showed high construct validity by emotional and behavioral outcomes. Conclusions: The stigma instrument showed high validity when compared to emotional and behavioral outcomes.

Patterned two-photon (2P) photolysis via holographic illumination is a powerful method to investigate neuronal function because of its capability to emulate multiple synaptic inputs in three dimensions (3D) simultaneously. However, like any optical system, holographic projectors have a finite space-bandwidth product that restricts the spatial range of patterned illumination or field-of-view (FOV) for a desired resolution. Such trade-off between holographic FOV and resolution restricts the coverage within a limited domain of the neuron's dendritic tree to perform highly resolved patterned 2P photolysis on individual spines. Here, we integrate a holographic projector into a commercial 2P galvanometer-based 2D scanning microscope with an uncaging unit and extend the accessible holographic FOV by using the galvanometer scanning mirrors to reposition the holographic FOV arbitrarily across the imaging FOV. The projector system utilizes the microscope's built-in imaging functions. Stimulation positions can be selected from within an acquired 3D image stack (the volume-of-interest, VOI) and the holographic projector then generates 3D illumination patterns with multiple uncaging foci. The imaging FOV of our system is 800×800 μm2 within which a holographic VOI of 70×70×70 μm3 can be chosen at arbitrary positions and also moved during experiments without moving the sample. We describe the design and alignment protocol as well as the custom software plugin that controls the 3D positioning of stimulation sites. We demonstrate the neurobiological application of the system by simultaneously uncaging glutamate at multiple spines within dendritic domains and consequently observing summation of postsynaptic potentials at the soma, eventually resulting in action potentials. At the same time, it is possible to perform two-photon Ca2+ imaging in 2D in the dendrite and thus to monitor synaptic Ca2+ entry in selected spines and also local regenerative events such as dendritic action potentials.

Background: There are few validated tools to measure adherence for children living with HIV. We identified questionnaire items for caregivers of Kenyan children aged

The security sector reform literature is increasingly turning towards the inclusion of non-state security providers, but the long-term patterns of political development to which such engagement might contribute remain underexplored. This article thus provides several lenses with which to understand the relationship between non-state security provision and political development. It first presents three perspectives (functionalism, political economy, and communitarianism) with which to understand the nature and behavior of non-state security providers. Second, it outlines five possible long-term trajectories of political formation and the role of non-state security providers in each. These discussions highlight the idea of hybridity, and the remainder of the paper argues that the concept can be usefully applied in (at least) two ways. The third section proposes that hybridity can help overcome longstanding but misleading conceptual binaries, while the fourth rearticulates hybridity as a dynamic developmental process – 'hybridization' – that can be contrasted with security politics as the underlying logic by which security providers (both state and non-state) interact and change over time.

Broadly neutralizing antibodies targeting the stalk region of influenza A virus (IAV) hemagglutinin (HA) are effective in blocking virus infection both in vitro and in vivo. The highly conserved epitopes recognized by these antibodies are critical for the membrane fusion function of HA and therefore less likely to be permissive for virus mutational escape. Here we report three resistant viruses of the A/Perth/16/2009 strain that were selected in the presence of a broadly neutralizing stalk-binding antibody. The three resistant viruses harbor three different mutations in the HA stalk: (1) Gln387Lys; (2) Asp391Tyr; (3) Asp391Gly. The Gln387Lys mutation completely abolishes binding of the antibody to the HA stalk epitope. The other two mutations, Asp391Tyr and Asp391Gly, do not affect antibody binding at neutral pH and only slightly reduce binding at low pH. Interestingly, they enhance the fusion ability of the HA, representing a novel mechanism that allows productive membrane fusion even in the presence of antibody and hence virus escape from antibody neutralization. Therefore, these mutations illustrate two different resistance mechanisms used by IAV to escape broadly neutralizing stalk-binding antibodies. Compared to the wild type virus, the resistant viruses release fewer progeny viral particles during replication and are more sensitive to Tamiflu, suggesting reduced viral fitness.

Analysis of splice variants from short read RNA-seq data remains a challenging problem. Here we present a novel method for the genome-guided prediction and quantification of splice events from RNA-seq data, which enables the analysis of unannotated and complex splice events. Splice junctions and exons are predicted from reads mapped to a reference genome and are assembled into a genome-wide splice graph. Splice events are identified recursively from the graph and are quantified locally based on reads extending across the start or end of each splice variant. We assess prediction accuracy based on simulated and real RNA-seq data, and illustrate how different read aligners (GSNAP, HISAT2, STAR, TopHat2) affect prediction results. We validate our approach for quantification based on simulated data, and compare local estimates of relative splice variant usage with those from other methods (MISO, Cufflinks) based on simulated and real RNA-seq data. In a proof-of-concept study of splice variants in 16 normal human tissues (Illumina Body Map 2.0) we identify 249 internal exons that belong to known genes but are not related to annotated exons. Using independent RNA samples from 14 matched normal human tissues, we validate 9/9 of these exons by RT-PCR and 216/249 by paired-end RNA-seq (2 x 250 bp). These results indicate that de novo prediction of splice variants remains beneficial even in well-studied systems. An implementation of our method is freely available as an R/Bioconductor package [Formula: see text].

Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD) pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y) cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

Cannabis use is increasingly pervasive among adolescents today, even more common than cigarette smoking. The evolving policy surrounding the legalization of cannabis reaffirms the need to understand the relationship between cannabis exposure early in life and psychiatric illnesses. Cannabis contains psychoactive components, notably Δ9-tetrahydrocannbinol (THC), that interfere with the brain’s endogenous endocannabinoid system, which is critically involved in both pre- and post-natal neurodevelopment. Consequently, THC and related compounds could potentially usurp normal adolescent neurodevelopment, shifting the brain’s developmental trajectory towards a disease-vulnerable state, predisposing early cannabis-users to motivational, affective and psychotic disorders. Numerous human studies, including prospective longitudinal studies, demonstrate that early cannabis use is associated with major depressive disorder and drug addiction. A strong association between schizophrenia and cannabis use is also apparent, especially when considering genetic factors that interact with this environmental exposure. These human studies set a foundation for carefully controlled animal studies which demonstrate similar patterns following early cannabinoid exposure. Given the vulnerable nature of adolescent neurodevelopment and the persistent changes that follow early cannabis exposure, the experimental findings outlined should be carefully considered by policymakers. In order to fully address the growing issues of psychiatric illnesses and to ensure a healthy future, measures should be taken to reduce cannabis use among teens.

We describe Bioconductor infrastructure for representing and computing on annotated genomic ranges and integrating genomic data with the statistical computing features of R and its extensions. At the core of the infrastructure are three packages: IRanges, GenomicRanges, and GenomicFeatures. These packages provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization.

Graphical user interfaces (GUIs) are growing in popularity as a complement or alternative to the traditional command line interfaces to R. RGtk2 is an R package for creating GUIs in R. The package provides programmatic access to GTK+ 2.0, an open-source GUI toolkit written in C. To construct a GUI, the R programmer calls RGtk2 functions that map to functions in the underlying GTK+ library. This paper introduces the basic concepts underlying GTK+ and explains how to use RGtk2 to construct GUIs from R. The tutorial is based on simple and pratical programming examples. We also provide more complex examples illustrating the advanced features of the package. The design of the RGtk2 API and the low-level interface from R to GTK+ are discussed at length. We compare RGtk2 to alternative GUI toolkits for R.

The datasets being produced by high-throughput biological experiments, such as microarrays, have forced biologists to turn to sophisticated statistical analysis and visualization tools in order to understand their data. We address the particular need for an open-source exploratory data analysis tool that applies numerical methods in coordination with interactive graphics to the analysis of experimental data. The software package, known as explorase, provides a graphical user interface (GUI) on top of the R platform for statistical computing and the GGobi software for multivariate interactive graphics. The GUI is designed for use by biologists, many of whom are unfamiliar with the R language. It displays metadata about experimental design and biological entities in tables that are sortable and filterable. There are menu shortcuts to the analysis methods implemented in R, including graphical interfaces to linear modeling tools. The GUI is linked to data plots in GGobi through a brush tool that simultaneously colors rows in the entity information table and points in the GGobi plots.

Staff in skilled nursing facilities (SNFs) are essential health care workers, yet they can also be a source of COVID-19 transmission. We used detailed staffing data to examine the relationship between a novel measure of staff size (that is, the number of unique employees working daily), conventional measures of staffing quality, and COVID-19 outcomes among SNFs in the United States without confirmed COVID-19 cases by June 2020. By the end of September 2020, sample SNFs in the lowest quartile of staff size had 6.2 resident cases and 0.9 deaths per 100 beds, compared with 11.9 resident cases and 2.1 deaths per 100 beds among facilities in the highest quartile. Staff size, including staff members not involved in resident care, was strongly associated with SNFs' COVID-19 outcomes, even after facility size was accounted for. Conventional staffing quality measures, including direct care staff-to-resident ratios and skill mix, were not significant predictors of COVID-19 cases or deaths. Reducing the number of unique staff members without decreasing direct care hours, such as by relying on full-time rather than part-time staff, could help prevent outbreaks.

Black learners and workers face particular disadvantages in the labor market: casual and explicit racism, stereotypes about skills and professionalism, and limited access to the social networks and social capital required to connect to opportunity. Numerous research studies confirm that Black employees in the same fields and with the same degrees as their White counterparts earn substantially less. This article examines the growing field of short-term noncredit credentials and asks for whom and under what circumstances they are a good choice. Do such credentials teach enough about how work "works" to put completers on a path to economic mobility despite the barriers they may face? The authors also ask what higher education institutions can contribute to student access to good jobs and economic mobility. They focus on how Black learners might best navigate the many available options rather than assume that short-term credentials are the best choice for these learners while their White peers choose bachelor's degrees.