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The Government Performance and Results Act (GPRA) mandates inclusion of evaluation in federal agency strategic plans, impacting human service programs receiving federal support. Recommended evaluation methods include flexible ongoing and participatory approaches. Yet social work may not be prepared to appropriately respond to the government's demands for accountability. This paper reviews GPRA and its implications for social work practice, evaluation, and research, offering response strategies. The paper suggests that the creation of a National Center for Social Work Research (S. 70/H.R. 663) could help bridge evaluation gaps, offering a centralized mechanism for monitoring evaluation activities and maximizing federal research resources. [ABSTRACT FROM AUTHOR]

In the era of precision health, nursing research has increasingly focused on the analysis of large, multidimensional data sets containing multiple correlated phenotypes (e.g., symptoms). This presents challenges for statistical analyses, especially in genetic association studies. For example, the inclusion of multiple symptoms within a single model can raise concerns about multicollinearity, while individual SNP-symptom analyses may obscure complex relationships. As such, many traditional statistical approaches often fall short in providing a comprehensive understanding of the complexity inherent in many nursing-focused research questions. Multivariate Bayesian approaches offer the unique advantage of allowing researchers to ask questions that are not feasible with traditional approaches. Specifically, these methods support the simultaneous exploration of multiple phenotypes, accounting for the underlying correlational structure between variables, and allow for formal incorporation of existing knowledge into the statistical model. By doing so, they may provide a more realistic view of statistical relationships within a biological system , potentially uncovering new insights into well-established and undiscovered connections, such as the probabilities of association and direct versus indirect effects. This valuable information can help us better understand our phenotypes of interest, leading to more effective nurse-led intervention and prevention programs. To illustrate these concepts, this paper includes an application section covering two specific multivariate Bayesian analysis software programs, bnlearn and mvBIMBAM , with an emphasis on interpretation and extension to nursing research. To complement the paper, we provide access to a detailed online tutorial, including executable R code and a synthetic data set, so the concepts can be more easily extended to other research questions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Here, we describe patterns of reproduction and flight phenology of putative Phloeosinus punctatus in giant sequoia groves and compare morphology and genotypes of beetles from sympatric giant sequoia (Sequoiadendron giganteum) and California incense-cedar (Calocedrus decurrens). Surveys conducted in 2022 revealed that numerous branches fall from giant sequoia crowns (on average ~30 branches/tree), with 20%-50% of trees per site shedding branches, depositing breeding material for beetles on the forest floor that subsequently becomes colonized. When noninfested branches cut from mature giant sequoias were placed at the ground surface, they were colonized by P. punctatus and produced an average of 28 beetles/kg branch. Climbing and examination of sequoia crowns in 2023 showed that 75% of mature trees across 11 groves showed evidence of adult beetle entrance holes in their crowns. In 2021, tests with sticky traps showed that beetles alighted on fallen branches from 20th May to 20th August (peak landing: 2nd July); a logistic model developed from emergence data in 2021 and 2022 predicts the emergence of F1 offspring from branches between 10th July and 1st September (peak emergence: 8th August). Beetles emerging from giant sequoia preferred to settle on giant sequoia, did not reproduce in incense-cedar, and diverged morphologically from beetles emerging from incense-cedar. However, phylogenetic analysis of three genes (28S, CAD, and COI) revealed no clear pattern of sequence divergence, suggesting a single species (P. punctatus) that colonizes both hosts, though cryptic speciation may not be detectable with standard barcoding genes. Ecological and potential management implications are discussed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America.)

Understanding the spatiotemporal dynamics of neural signal propagation is fundamental to unraveling the complexities of brain function. Emerging evidence suggests that cortico-cortical evoked potentials (CCEPs) resulting from single-pulse electrical stimulation may be used to characterize the patterns of information flow between and within brain networks. At present, the basic spatiotemporal dynamics of CCEP propagation cortically and subcortically are incompletely understood. We hypothesized that single-pulse electrical stimulation evokes neural traveling waves detectable in the three-dimensional space sampled by intracranial stereoelectroencephalography. Across a cohort of 21 adult patients with intractable epilepsy, we delivered 17,631 stimulation pulses and recorded CCEP responses in 1,019 electrode contacts. The distance between each pair of electrode contacts was approximated using three different metrics (Euclidean distance, path length, and geodesic distance), representing direct, tractographic, and transcortical propagation, respectively. For each robust CCEP, we extracted amplitude-, spectral-, and phase-based features to identify traveling waves emanating from the site of stimulation. Many evoked responses to stimulation appear to propagate as traveling waves (~14-28%), despite sparse sampling throughout the brain. These stimulation-evoked traveling waves exhibited biologically plausible propagation velocities (range 0.1-9.6 m/s). Our results reveal that direct electrical stimulation elicits neural activity with variable spatiotemporal dynamics, including the initiation of neural traveling waves., Competing Interests: Conflicts of Interest: None

Background: Mastoiditis frequently occurs in children as they are more susceptible to middle ear infections, but infrequently occurs in adults. A rare complication that results from mastoiditis and an obstructing cholesteatoma is a Bezold's abscess, of which there are less than 100 reported cases in literature to date., Case Presentation: Here, we present a case of a 72-year-old Caucasian man who has had no history of prior ear infections and was found to have a cholesteatoma and advanced acute coalescent mastoiditis complicated by a Bezold's abscess., Conclusions: Bezold's abscess is a rare entity infrequently encountered in the modern era, likely owing to more prompt treatment of otitis media. Cholesteatoma poses a great risk for both the development of otitis media and further progression to mastoiditis and its associated complications, such as Bezold's abscess. Knowledge of said abscess is crucial; without prompt recognition, further spread of infection can occur with vascular or mediastinal involvement., (© 2024. The Author(s).)

Objectives: To explore genes in the nuclear factor E2-related factor 2 antioxidative response elements (Nrf2-ARE) signaling pathway using a multiomics approach for associations with variability of cancer-related fatigue (CRF) in postmenopausal women with early-stage hormone receptor-positive breast cancer., Sample & Setting: Postmenopausal women (N = 116) with early-stage hormone receptor-positive breast cancer were recruited from western Pennsylvania., Methods & Variables: Candidate genes from the Nrf2-ARE pathway were investigated for associations with CRF occurrence and severity. Associations were evaluated using logistic regression for occurrence and linear regression for severity., Results: The rs2706110 TT genotype in NFE2L2 was associated with a 3.5-fold increase in odds of CRF occurrence. The cytosine-phosphate-guanine (CpG) site cg22820568 in PRDX1 was associated with CRF occurrence and severity., Implications for Nursing: Biomarkers based on Nrf2-ARE genes may help to identify women at increased risk for more severe CRF and to develop targeted interventions.

Objective: Interictal epileptiform discharges (IEDs) are intermittent high-amplitude electrical signals that occur between seizures. They have been shown to propagate through the brain as traveling waves when recorded with epicortical grid-type electrodes and small penetrating microelectrode arrays. However, little work has been done to translate experimental IED analyses to more clinically relevant platforms such as stereoelectroencephalography (SEEG). In this pilot study, the authors aimed to define a computational method to identify and characterize IEDs recorded from clinical SEEG electrodes and leverage the directionality of IED traveling waves to localize the seizure onset zone (SOZ)., Methods: Continuous SEEG recordings from 15 patients with medically refractory epilepsy were collected, and IEDs were detected by identifying overlapping peaks of a minimum prominence. IED pathways of propagation were defined and compared to the SOZ location determined by a clinical neurologist based on the ictal recordings. For further analysis of the IED pathways of propagation, IED detections were divided into triplets, defined as a set of 3 consecutive contacts within the same IED detection. Univariate and multivariate linear regression models were employed to associate IED characteristics with colocalization to the SOZ., Results: A median (range) of 22.6 (4.4-183.9) IEDs were detected per hour from 15 patients over a mean of 23.2 hours of recording. Depending on the definition of the SOZ, a median (range) of 20.8% (0.0%-54.5%) to 62.1% (19.2%-99.4%) of IEDs per patient traversed the SOZ. IEDs passing through the SOZ followed discrete pathways that had little overlap with those of the IEDs passing outside the SOZ. Contact triplets that occurred more than once were significantly more likely to be detected in an IED passing through the SOZ (p < 0.001). Per our multivariate model, patients with a greater proportion of IED traveling waves had a significantly greater proportion of IEDs that localized to the SOZ (β = 0.64, 95% CI 0.01-1.27, p = 0.045)., Conclusions: By using computational methods, IEDs can be meaningfully detected from clinical-grade SEEG recordings of patients with epilepsy. In some patients, a high proportion of IEDs are traveling waves according to multiple metrics that colocalize to the SOZ, offering hope that IED detection, with further refinement, could serve as an alternative method for SOZ localization.

Objectives: Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS., Methods: We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up., Results: Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures)., Significance: These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Orodynia (OD) manifests as an unexplained burning sensation in the oral cavity, often persisting for years without clear clinical findings. Currently, there is no clear protocol for managing OD. We propose a systematic approach that aims to exclude common potential causes and attempt proactive treatments. Anecdotally, we have found that our structured approach improves clinical outcomes.

The genus Dendroctonus is a Holarctic taxon composed of 21 nominal species; some of these species are well known in the world as disturbance agents of forest ecosystems. Under the bark of the host tree, these insects are involved in complex and dynamic associations with phoretic ectosymbiotic and endosymbiotic communities. Unlike filamentous fungi and bacteria, the ecological role of yeasts in the bark beetle holobiont is poorly understood, though yeasts were the first group to be recorded as microbial symbionts of these beetles. Our aim was characterize and compare the gut fungal assemblages associated to 14 species of Dendroctonus using the internal transcribed spacer 2 (ITS2) region. A total of 615,542 sequences were recovered yielding 248 fungal amplicon sequence variants (ASVs). The fungal diversity was represented by 4 phyla, 16 classes, 34 orders, 54 families, and 71 genera with different relative abundances among Dendroctonus species. The α-diversity consisted of 32 genera of yeasts and 39 genera of filamentous fungi. An analysis of β-diversity indicated differences in the composition of the gut fungal assemblages among bark beetle species, with differences in species and phylogenetic diversity. A common core mycobiome was recognized at the genus level, integrated mainly by Candida present in all bark beetles, Nakazawaea , Cladosporium , Ogataea , and Yamadazyma . The bipartite networks confirmed that these fungal genera showed a strong association between beetle species and dominant fungi, which are key to maintaining the structure and stability of the fungal community. The functional variation in the trophic structure was identified among libraries and species, with pathotroph-saprotroph-symbiotroph represented at the highest frequency, followed by saprotroph-symbiotroph, and saprotroph only. The overall network suggested that yeast and fungal ASVs in the gut of these beetles showed positive and negative associations among them. This study outlines a mycobiome associated with Dendroctonus nutrition and provides a starting point for future in vitro and omics approaches addressing potential ecological functions and interactions among fungal assemblages and beetle hosts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pineda-Mendoza, Gutiérrez-Ávila, Salazar, Rivera-Orduña, Davis and Zúñiga.)

In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In North American conifer forests, a variety of federally initiated thinning programs are implemented to restore pre-European settlement forest structures, but these changes may impact ecosystem function via impacts on sensitive biotic communities. Across the wildland-urban interface of the Front Range region of Colorado, agencies associated with the Collaborative Forest Landscape Restoration Program (CFLRP) have implemented thinning treatments across thousands of hectares of ponderosa pine forest; here we leverage these treatments as an experimental framework to examine thinning effects on a pollinator community. We measured variation in forest structure and sampled bee community assemblages using multiple methods (trapping and netting) to compare bee biodiversity and patterns of floral visitation by bees (bee-flower networks) between mechanically thinned stands that were 3-10 years after treatment and nonthinned stands. Three key findings emerged: (1) Native bee abundance, richness, and diversity were 120%, 53%, and 37% greater, respectively, in thinned stands. In addition, nestedness, richness, and abundance of bee-flower interactions were all substantially higher in thinned stands, and there was increased functional redundancy in bee assemblages after thinning. (2) Structural equation modeling indicated that variation in temperature and floral abundance were mediated by canopy openness and correlated with bee richness and abundance, thereby indirectly driving variation in bee-flower interactions. (3) Four floral species (Penstemon virens, Cerastium arvense, Erysimum capitatum, and Geranium caespitosum) were identified as key connectors in bee-flower interaction networks, though these were not necessarily the most abundant flowering plants. Our analyses indicate that native bee α-diversity and bee-flower interactions positively responded to thinning treatments, and these effects were indirectly driven by canopy removal. We conclude that CFLRP treatments have conservation value for native bee communities. Further monitoring is warranted to evaluate the longevity of these effects., (© 2023 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Pain is a complex experience involving sensory, emotional, and cognitive aspects, and multiple networks manage its processing in the brain. Examining how pain transforms into a behavioral response can shed light on the networks' relationships and facilitate interventions to treat chronic pain. However, studies using high spatial and temporal resolution methods to investigate the neural encoding of pain and its psychophysical correlates have been limited. We recorded from intracranial stereo-EEG (sEEG) electrodes implanted in sixteen different brain regions of twenty patients who underwent psychophysical pain testing consisting of a tonic thermal stimulus to the hand. Broadband high-frequency local field potential amplitude (HFA; 70-150 Hz) was isolated to investigate the relationship between the ongoing neural activity and the resulting psychophysical pain evaluations. Two different generalized linear mixed-effects models (GLME) were employed to assess the neural representations underlying binary and graded pain psychophysics. The first model examined the relationship between HFA and whether the patient responded "yes" or "no" to whether the trial was painful. The second model investigated the relationship between HFA and how painful the stimulus was rated on a visual analog scale. GLMEs revealed that HFA in the inferior temporal gyrus (ITG), superior frontal gyrus (SFG), and superior temporal gyrus (STG) predicted painful responses at stimulus onset. An increase in HFA in the orbitofrontal cortex (OFC), SFG, and striatum predicted pain responses at stimulus offset. Numerous regions, including the anterior cingulate cortex, hippocampus, IFG, MTG, OFC, and striatum, predicted the pain rating at stimulus onset. However, only the amygdala and fusiform gyrus predicted increased pain ratings at stimulus offset. We characterized the spatiotemporal representations of binary and graded painful responses during tonic pain stimuli. Our study provides evidence from intracranial recordings that the neural encoding of psychophysical pain changes over time during a tonic thermal stimulus, with different brain regions being predictive of pain at the beginning and end of the stimulus., Competing Interests: JDR has received consulting fees from Medtronic, NeuroPace, and Corlieve Therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Caston et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To better understand functional ecology of bark beetle-microbial symbioses, we characterized yeast associates of North American spruce beetle (Dendroctous rufipennis Kirby) across populations. Seven yeast species were detected; Wickerhamomyces canadensis (Wickerham) Kurtzman et al. (Sachharomycetales: Saccharomycetaceae) was the most common (74% of isolates) and found in all populations. Isolates of W. canadensis were subsequently tested for competitive interactions with symbiotic (Leptographium abietinum, = Grosmannia abietina) and pathogenic (Beauvaria bassiana) filamentous fungi, and isolates were nutritionally profiled (protein and P content). Exposure to yeast headspace emissions had isolate-dependent effects on colony growth of symbiotic and pathogenic fungi; most isolates of W. canadensis slightly inhibited growth rates of symbiotic (L. abietinum, mean effect: - 4%) and entomopathogenic (B. bassiana, mean effect: - 6%) fungi. However, overall variation was high (range: - 35.4 to + 88.6%) and some yeasts enhanced growth of filamentous fungi whereas others were consistently inhibitory. The volatile 2-phenylethanol was produced by W. canadensis and synthetic 2-phenylethanol reduced growth rates of both L. abietinum and B. bassiana by 36% on average. Mean protein and P content of Wickerhamomyces canadensis cultures were 0.8% and 7.2%, respectively, but isolates varied in nutritional content and protein content was similar to that of host tree phloem. We conclude that W. canadensis is a primary yeast symbiont of D. rufipennis in the Rocky Mountains and emits volatiles that can affect growth of associated microbes. Wickerhamomyces canadensis isolates vary substantially in limiting nutrients (protein and P), but concentrations are less than reported for the symbiotic filamentous fungus L. abietinum., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Social determinants of health (SDoH) impact health and wellness. The link between SDoH and adverse health outcomes, including symptom occurrence and severity, may be explained by an individual's physiologic response to one or more SDoH. One potential mechanism underlying this physiologic response linking SDoH and symptoms is the dynamic epigenome. The purpose of this scoping review of the literature was to examine differential susceptibility for symptoms by identifying and summarizing research linking SDoH and symptoms through epigenomic mechanisms. PubMed was searched to identify empirical research where at least one SDoH was an independent or dependent variable, at least one symptom was investigated, and the investigation included an epigenomic measure. Of the 484 articles initially retrieved, after thorough vetting, 41 articles met eligibility. The most studied symptom was depressive symptoms followed by anxiety, cognitive function, sleep dysfunction, and pain. The most frequently studied SDoH were: 1) stress, particularly early life stress and acculturative stress; and 2) trauma, predominantly childhood trauma. DNA methylation and telomere length were the most studied epigenomic measures. Four genes ( SLC6A4, BDNF, NR3C1, OXTR ) had evidence from multiple studies and across methodological approaches linking SDoH to symptoms. This review supports the inclusion of epigenomic approaches to better understand the link between SDoH and symptoms and provides evidence that SDoH impact telomere length and the methylation of genes involved in neurotransmitter signaling, neuronal survival, behavior, inflammation and stress response.

Abstract: The concept for creating the Northeastern Society of Plastic Surgeons originated in May 1982, at the American Association of Plastic Surgeons in Colorado Springs Colorado. The new society would supplement, not supplant, existing state and small regional societies. Two hundred fifty-seven northeastern plastic surgeons joined the charter membership. The inaugural meeting of the Northeastern Society of Plastic Surgeons was held in Philadelphia, September 1984. The following historical account highlights our society's founding principles and leadership throughout the first 40 years., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study examined the feasibility, acceptability, and preliminary effectiveness of an oncology financial navigation (OFN) intervention, Coverage and Cost-of-Care Links ( CC Links ), among patients with hematologic cancer and their caregivers who are at increased risk of experiencing financial toxicity (FT)., Methods: All patients who presented to the Division of Hematology and Bone and Marrow Transplant (BMT) at an National Cancer Institute-designated cancer center between April 2021 and January 2022 were screened for FT during inpatient and outpatient visits. Patients who screened positive for FT and met the inclusion criteria were recruited to participate in CC Links that provided financial navigation and assistance via a financial navigator. Caregivers of patients undergoing BMTs were also recruited to participate. Primary outcomes were defined as improvements in FT, distress, and physical and mental quality of life., Results: Fifty-four patients and 32 caregivers completed the intervention and pre-/postintervention surveys. CC Links resulted in statistically significant decreases in the Comprehensive Score for FT for both patients (| t | = 2.42, P = .019) and caregivers (| t | = 2.43, P = .021) and total FT (| t | = 2.13, P = .041) and material conditions scores (| t | = 2.25, P = .031) for caregivers only. Only 27% of eligible patients participated in the study, whereas 100% of eligible caregivers participated. The majority of participants rated the intervention highly for acceptability (89%) and appropriateness (88%). An average of $2,500 (USD) in financial benefits was secured per participant via CC Links., Conclusion: CC Links was effective in decreasing FT among patients with hematologic cancer and their caregivers while demonstrating high acceptability and appropriateness ratings.

Epigenomic modifications of the brain-derived neurotrophic factor (BDNF) gene have been postulated to underlie the pathogenesis of neurodevelopmental, psychiatric, and neurological conditions. This systematic review summarizes current evidence investigating the association of BDNF epigenomic modifications (DNA methylation, non-coding RNA, histone modifications) with brain-related phenotypes in humans. A novel contribution is our creation of an open access web-based application, the BDNF DNA Methylation Map, to interactively visualize specific positions of CpG sites investigated across all studies for which relevant data were available. Our literature search of four databases through September 27, 2021 returned 1701 articles, of which 153 met inclusion criteria. Our review revealed exceptional heterogeneity in methodological approaches, hindering the identification of clear patterns of robust and/or replicated results. We summarize key findings and provide recommendations for future epigenomic research. The existing literature appears to remain in its infancy and requires additional rigorous research to fulfill its potential to explain BDNF-linked risk for brain-related conditions and improve our understanding of the molecular mechanisms underlying their pathogenesis., Competing Interests: Declaration of Competing Interest Dr. Treble-Barna, Dr. Heinsberg, Dr. Weeks, Dr. Conley, Dr. Breazeale, and Ms. Davis reported receiving grants from the NIH during the conduct of the study. Dr. Kochanek reported receiving grants from the NIH, the U.S. Department of Defense, the Chuck Noll foundation, the Laerdal Foundation, and the Zoll Foundation during the conduct of the study and serves as an expert witness in cases related to neurocritical care and traumatic brain injury. Dr. Yeates reported receiving grant support from the Ronald and Irene Ward Chair in Pediatric Brain injury from Alberta Children's Hospital Foundation., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Cerebral projections of nociceptive stimuli are of great interest as targets for neuromodulation in chronic pain. To study cerebral networks involved in processing noxious stimuli, researchers often rely on thermo-nociception to induce pain. However, various limitations exist in many pain-inducing techniques, such as not accounting for individual variations in pain and trial structure predictability., Methods: We propose an improved and reliable psychometric experimental method to evaluate human nociceptive processing to overcome some of these limitations. The developed testing paradigm leverages a custom-built, open-source, thermoelectric device (TED). The device construction and hardware are described. A maximum-likelihood adaptive algorithm is integrated into the TED software, facilitating individual psychometric functions representative of both hot and cold pain perception. In addition to testing only hot or cold thresholds, the TED may also be used to induce the thermal grill illusion (TGI), where the bars are set to alternating warm and cool temperatures., Results: Here, we validated the TED's capability to adjust between different temperatures and showed that the device quickly and automatically changes temperature without any experimenter input. We also validated the device and integrated psychometric pain task in 21 healthy human subjects. Hot and cold pain thresholds (HPT, CPT) were determined in human subjects with <1 °C of variation. Thresholds were anticorrelated, meaning a volunteer with a low CPT likely had a high HPT. We also showed how the TED can be used to induce the TGI., Conclusion: The TED can induce thermo-nociception and provide probabilistic measures of hot and cold pain thresholds. Based on the findings presented, we discuss how the TED could be used to study thermo-nociceptive cerebral projections if paired with intracranial electrode monitoring., Competing Interests: Declaration of Competing Interest We have no competing interests. Disclosures are mentioned in the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction The objective of this study was to identify barriers that affect adherence to the management of diabetic retinopathy (DR) in an urban ophthalmology clinic. Patient beliefs regarding diabetic eye care, transportation to the eye clinic, the COVID-19 pandemic, and treatment with panretinal photocoagulation (PRP) or anti-vascular endothelial growth factor (anti-VEGF) injections were investigated. Materials and methods The original Compliance with Annual Diabetic Eye Exams Survey (CADEES) included 44 statements designed with a 5-point Likert scale to assess patients' beliefs and understanding of their eye health and the importance of diabetic eye examinations. This survey was modified to include additional statements regarding the COVID-19 pandemic and free-response questions about transportation barriers and patients' subjective experiences with PRP or anti-VEGF injections. A total of 365 patients with a diagnosis of any stage of DR from SLUCare Ophthalmology were identified as potential participants to complete the telephone survey. Patients were classified as non-adherent if they did not have a dilated eye examination within the past year, missed a scheduled follow-up appointment for DR care within the past year, or missed an appointment for anti-VEGF injections or PRP. The mean Likert scores for each CADEES statement were compared between the adherent and non-adherent groups using independent samples t-tests. Demographics and clinical indicators were also reported and compared between the two groups. Results Out of 365 patients, 68 completed the modified CADEES. Twenty-nine patients were adherent, and 39 patients were non-adherent. Results from six of the 54 CADEES statements were significantly different between the adherent and non-adherent groups. These statements addressed patients' perception of their eye health, self-confidence in making an eye appointment, knowing someone with diabetic eye complications, self-confidence in controlling blood sugar, ability to use public transportation during the COVID-19 pandemic, and prioritizing eye health during the pandemic. There were no significant differences in clinical indicators or demographics between the adherent and non-adherent groups. Of the participants, 39.7% offered reasons for why transportation to the eye clinic was difficult. Patients suggested three novel reasons for missing eye appointments that were not specifically addressed in the CADEES. Fourteen unique barriers were reported for non-adherence with PRP or anti-VEGF injections. Conclusions The CADEES is a thorough tool for evaluating social barriers impacting adherence with DR appointments in an urban ophthalmology clinic. The survey did not identify any clinical or demographic risk factors for non-adherence in this patient population. Decreased patient self-efficacy may lead to non-adherence with the management of DR. The COVID-19 pandemic impacted the adherence of a small percentage of patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Davis et al.)

A changing climate is altering ecosystem carbon dynamics with consequences for natural systems and human economies, but there are few tools available for land managers to meaningfully incorporate carbon trajectories into planning efforts. To address uncertainties wrought by rapidly changing conditions, many practitioners adopt resistance and resilience as ecosystem management goals, but these concepts have proven difficult to monitor across landscapes. Here, we address the growing need to understand and plan for ecosystem carbon with concepts of resistance and resilience. Using time series of carbon fixation (n = 103), we evaluate forest management treatments and their relative impacts on resistance and resilience in the context of an expansive and severe natural disturbance. Using subalpine spruce-fir forest with a known management history as a study system, we match metrics of ecosystem productivity (net primary production, g C m -2  year -1 ) with site-level forest structural measurements to evaluate (1) whether past management efforts impacted forest resistance and resilience during a spruce beetle (Dendroctonus rufipennis) outbreak, and (2) how forest structure and physiography contribute to anomalies in carbon trajectories. Our analyses have several important implications. First, we show that the framework we applied was robust for detecting forest treatment impacts on carbon trajectories, closely tracked changes in site-level biomass, and was supported by multiple evaluation methods converging on similar management effects on resistance and resilience. Second, we found that stand species composition, site productivity, and elevation predicted resistance, but resilience was only related to elevation and aspect. Our analyses demonstrate application of a practical approach for comparing forest treatments and isolating specific site and physiographic factors associated with resistance and resilience to biotic disturbance in a forest system, which can be used by managers to monitor and plan for both outcomes. More broadly, the approach we take here can be applied to many scenarios, which can facilitate integrated management and monitoring efforts., (© 2022 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of The Ecological Society of America. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Disturbances alter biodiversity via their specific characteristics, including severity and extent in the landscape, which act at different temporal and spatial scales. Biodiversity response to disturbance also depends on the community characteristics and habitat requirements of species. Untangling the mechanistic interplay of these factors has guided disturbance ecology for decades, generating mixed scientific evidence of biodiversity responses to disturbance. Understanding the impact of natural disturbances on biodiversity is increasingly important due to human-induced changes in natural disturbance regimes. In many areas, major natural forest disturbances, such as wildfires, windstorms, and insect outbreaks, are becoming more frequent, intense, severe, and widespread due to climate change and land-use change. Conversely, the suppression of natural disturbances threatens disturbance-dependent biota. Using a meta-analytic approach, we analysed a global data set (with most sampling concentrated in temperate and boreal secondary forests) of species assemblages of 26 taxonomic groups, including plants, animals, and fungi collected from forests affected by wildfires, windstorms, and insect outbreaks. The overall effect of natural disturbances on α-diversity did not differ significantly from zero, but some taxonomic groups responded positively to disturbance, while others tended to respond negatively. Disturbance was beneficial for taxonomic groups preferring conditions associated with open canopies (e.g. hymenopterans and hoverflies), whereas ground-dwelling groups and/or groups typically associated with shady conditions (e.g. epigeic lichens and mycorrhizal fungi) were more likely to be negatively impacted by disturbance. Across all taxonomic groups, the highest α-diversity in disturbed forest patches occurred under moderate disturbance severity, i.e. with approximately 55% of trees killed by disturbance. We further extended our meta-analysis by applying a unified diversity concept based on Hill numbers to estimate α-diversity changes in different taxonomic groups across a gradient of disturbance severity measured at the stand scale and incorporating other disturbance features. We found that disturbance severity negatively affected diversity for Hill number q = 0 but not for q = 1 and q = 2, indicating that diversity-disturbance relationships are shaped by species relative abundances. Our synthesis of α-diversity was extended by a synthesis of disturbance-induced change in species assemblages, and revealed that disturbance changes the β-diversity of multiple taxonomic groups, including some groups that were not affected at the α-diversity level (birds and woody plants). Finally, we used mixed rarefaction/extrapolation to estimate biodiversity change as a function of the proportion of forests that were disturbed, i.e. the disturbance extent measured at the landscape scale. The comparison of intact and naturally disturbed forests revealed that both types of forests provide habitat for unique species assemblages, whereas species diversity in the mixture of disturbed and undisturbed forests peaked at intermediate values of disturbance extent in the simulated landscape. Hence, the relationship between α-diversity and disturbance severity in disturbed forest stands was strikingly similar to the relationship between species richness and disturbance extent in a landscape consisting of both disturbed and undisturbed forest habitats. This result suggests that both moderate disturbance severity and moderate disturbance extent support the highest levels of biodiversity in contemporary forest landscapes., (© 2022 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Dendroctonus -bark beetles are associated with microbes that can detoxify terpenes, degrade complex molecules, supplement and recycle nutrients, fix nitrogen, produce semiochemicals, and regulate ecological interactions between microbes. Females of some Dendroctonus species harbor microbes in specialized organs called mycetangia; yet little is known about the microbial diversity contained in these structures. Here, we use metabarcoding to characterize mycetangial fungi from beetle species in the Dendroctonus frontalis complex, and analyze variation in biodiversity of microbial assemblages between beetle species. Overall fungal diversity was represented by 4 phyla, 13 classes, 25 orders, 39 families, and 48 genera, including 33 filamentous fungi, and 15 yeasts. The most abundant genera were Entomocorticium , Candida , Ophiostoma-Sporothrix , Ogataea , Nakazawaea , Yamadazyma , Ceratocystiopsis , Grosmannia-Leptographium , Absidia , and Cyberlindnera . Analysis of α-diversity indicated that fungal assemblages of D . vitei showed the highest richness and diversity, whereas those associated with D . brevicomis and D . barberi had the lowest richness and diversity, respectively. Analysis of β-diversity showed clear differentiation in the assemblages associated with D . adjunctus , D . barberi , and D . brevicomis , but not between closely related species, including D . frontalis and D . mesoamericanus and D . mexicanus and D . vitei . A core mycobiome was not statistically identified; however, the genus Ceratocystiopsis was shared among seven beetle species. Interpretation of a tanglegram suggests evolutionary congruence between fungal assemblages and species of the D . frontalis complex. The presence of different amplicon sequence variants (ASVs) of the same genus in assemblages from species of the D . frontalis complex outlines the complexity of molecular networks, with the most complex assemblages identified from D . vitei , D . mesoamericanus , D . adjunctus , and D . frontalis . Analysis of functional variation of fungal assemblages indicated multiple trophic groupings, symbiotroph/saprotroph guilds represented with the highest frequency (∼31% of identified genera). These findings improve our knowledge about the diversity of mycetangial communities in species of the D . frontalis complex and suggest that minimal apparently specific assemblages are maintained and regulated within mycetangia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vazquez-Ortiz, Pineda-Mendoza, González-Escobedo, Davis, Salazar, Rivera-Orduña and Zúñiga.)

Objective: Responsive neurostimulation is an effective therapy for patients with refractory mesial temporal lobe epilepsy. However, clinical outcomes are variable, few patients become seizure-free, and the optimal stimulation location is currently undefined. The aim of this study was to quantify responsive neurostimulation in the mesial temporal lobe, identify stimulation-dependent networks associated with seizure reduction, and determine if stimulation location or stimulation-dependent networks inform outcomes., Methods: We modeled patient-specific volumes of tissue activated and created probabilistic stimulation maps of local regions of stimulation across a retrospective cohort of 22 patients with mesial temporal lobe epilepsy. We then mapped the network stimulation effects by seeding tractography from the volume of tissue activated with both patient-specific and normative diffusion-weighted imaging. We identified networks associated with seizure reduction across patients using the patient-specific tractography maps and then predicted seizure reduction across the cohort., Results: Patient-specific stimulation-dependent connectivity was correlated with responsive neurostimulation effectiveness after cross-validation (p = .03); however, normative connectivity derived from healthy subjects was not (p = .44). Increased connectivity from the volume of tissue activated to the medial prefrontal cortex, cingulate cortex, and precuneus was associated with greater seizure reduction., Significance: Overall, our results suggest that the therapeutic effect of responsive neurostimulation may be mediated by specific networks connected to the volume of tissue activated. In addition, patient-specific tractography was required to identify structural networks correlated with outcomes. It is therefore likely that altered connectivity in patients with epilepsy may be associated with the therapeutic effect and that utilizing patient-specific imaging could be important for future studies. The structural networks identified here may be utilized to target stimulation in the mesial temporal lobe and to improve seizure reduction for patients treated with responsive neurostimulation., (© 2022 International League Against Epilepsy.)

Global temperatures are generally increasing, and this is leading to a well documented advancement and extension of seasonal activity of many pest insects. Effects of changing precipitation have received less attention, but might be complex because rain and snow are increasing in some places but decreasing in others. This raises the possibility that altered precipitation could accentuate, or even reverse, the effects of rising temperatures on pest outbreaks. We used >592 K aphid suction-trap captures over 15 years, in the heavily farmed central USA, to examine how the activity of Aphis glycines (soybean aphid), Rhopalosiphum maidis (corn aphid), and Rhopalosiphum padi (bird cherry-oat aphid) changed with variation in both temperature and precipitation. Increasing precipitation caused late-season flight activity of A. glycines and early-season activity of R. padi to shift earlier, while increasing temperature did the same for early-season activity of A. glycines and R. maidis. In these cases, precipitation and temperature exhibited directionally similar, but independent, effects. However, precipitation sometimes mediated temperature effects in complex ways. At relatively low temperatures, greater precipitation generally caused late-season flights of R. maidis to occur earlier. However, this pattern was reversed at higher temperatures with precipitation delaying late-season activity. In contrast, greater precipitation delayed peak flights of R. padi at lower temperatures, but caused them to occur earlier at higher temperatures. So, in these two cases the interactive effects of precipitation on temperature were mirror images of one another. When projecting future aphid flight phenology, models that excluded precipitation covariates consistently underpredicted the degree of phenological advance for A. glycines and R. padi, and underpredicted the degree of phenological delay for R. maidis under expected future climates. Overall, we found broad evidence that changing patterns of aphid flight phenology could only be understood by considering both temperature and precipitation changes. In our study region, temperature and precipitation are expected to increase in tandem, but these correlations will be reversed elsewhere. This reinforces the need to include both main and interactive effects of precipitation and temperature when seeking to accurately predict how pest pressure will change with a changing climate., (© 2022 The Ecological Society of America.)

In this study, we quantified the coverage of gray and white matter during intracranial electroencephalography in a cohort of epilepsy patients with surface and depth electrodes. We included 65 patients with strip electrodes (n = 12), strip and grid electrodes (n = 24), strip, grid, and depth electrodes (n = 7), or depth electrodes only (n = 22). Patient-specific imaging was used to generate probabilistic gray and white matter maps and atlas segmentations. Gray and white matter coverage was quantified using spherical volumes centered on electrode centroids, with radii ranging from 1 to 15 mm, along with detailed finite element models of local electric fields. Gray matter coverage was highly dependent on the chosen radius of influence (RoI). Using a 2.5 mm RoI, depth electrodes covered more gray matter than surface electrodes; however, surface electrodes covered more gray matter at RoI larger than 4 mm. White matter coverage and amygdala and hippocampal coverage was greatest for depth electrodes at all RoIs. This study provides the first probabilistic analysis to quantify coverage for different intracranial recording configurations. Depth electrodes offer increased coverage of gray matter over other recording strategies if the desired signals are local, while subdural grids and strips sample more gray matter if the desired signals are diffuse., (© 2021. The Author(s).)

Accurate anatomical localization of intracranial electrodes is important for identifying the seizure foci in patients with epilepsy and for interpreting effects from cognitive studies employing intracranial electroencephalography. Localization is typically performed by coregistering postimplant computed tomography (CT) with preoperative magnetic resonance imaging (MRI). Electrodes are then detected in the CT, and the corresponding brain region is identified using the MRI. Many existing software packages for electrode localization chain together separate preexisting programs or rely on command line instructions to perform the various localization steps, making them difficult to install and operate for a typical user. Further, many packages provide solutions for some, but not all, of the steps needed for confident localization. We have developed software, Locate electrodes Graphical User Interface (LeGUI), that consists of a single interface to perform all steps needed to localize both surface and depth/penetrating intracranial electrodes, including coregistration of the CT to MRI, normalization of the MRI to the Montreal Neurological Institute template, automated electrode detection for multiple types of electrodes, electrode spacing correction and projection to the brain surface, electrode labeling, and anatomical targeting. The software is written in MATLAB, core image processing is performed using the Statistical Parametric Mapping toolbox, and standalone executable binaries are available for Windows, Mac, and Linux platforms. LeGUI was tested and validated on 51 datasets from two universities. The total user and computational time required to process a single dataset was approximately 1 h. Automatic electrode detection correctly identified 4362 of 4695 surface and depth electrodes with only 71 false positives. Anatomical targeting was verified by comparing electrode locations from LeGUI to locations that were assigned by an experienced neuroanatomist. LeGUI showed a 94% match with the 482 neuroanatomist-assigned locations. LeGUI combines all the features needed for fast and accurate anatomical localization of intracranial electrodes into a single interface, making it a valuable tool for intracranial electrophysiology research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Davis, Caston, Philip, Charlebois, Anderson, Weaver, Smith and Rolston.)

BACKGROUNDA long-held goal of vision therapy is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists.METHODSWe implanted an intracortical microelectrode array consisting of 96 electrodes in the visual cortex of a 57-year-old person with complete blindness for a 6-month period. We measured thresholds and the characteristics of the visual percepts elicited by intracortical microstimulation.RESULTSImplantation and subsequent explantation of intracortical microelectrodes were carried out without complications. The mean stimulation threshold for single electrodes was 66.8 ± 36.5 μA. We consistently obtained high-quality recordings from visually deprived neurons and the stimulation parameters remained stable over time. Simultaneous stimulation via multiple electrodes was associated with a significant reduction in thresholds (P < 0.001, ANOVA) and evoked discriminable phosphene percepts, allowing the blind participant to identify some letters and recognize object boundaries.CONCLUSIONSOur results demonstrate the safety and efficacy of chronic intracortical microstimulation via a large number of electrodes in human visual cortex, showing its high potential for restoring functional vision in the blind.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02983370.FUNDINGThe Spanish Ministerio de Ciencia Innovación y Universidades, the Generalitat Valenciana (Spain), the Europan Union's Horizon 2020 programme, the Bidons Egara Research Chair of the University Miguel Hernández (Spain), and the John Moran Eye Center of the University of Utah.

Commercial prosthetic hands are frequently abandoned due to unintuitive control methods and a lack of sensory feedback from the prosthesis. Advanced neuromyoelectric prostheses can restore intuitive control and sensory feedback to prosthesis users and potentially reduce abandonment. However, not all advanced prosthetic systems are deployable for home use on portable systems with limited computational power. In this work, we use a commercially available portable neural interface processor (the Ripple Neuro Nomad), and a multi-degree-of-freedom bionic arm (the DEKA LUKE Arm) to create a closed-loop neuromyoelectric prosthesis. The system restores intuitive, independent, continuous control over the arm's six-degrees-of-freedom and provides sensory feedback for up to 288 neural and six vibrotactile channels. Additionally, the large storage capacity of the system enables high-resolution logging of EMG, hand positions, prosthesis sensors, and stimulation parameters. We developed two GUIs enabling wireless, real-time adjustments to motor control and feedback parameters: one with nearly full control over motor control and feedback parameters for investigators, and one with restricted capabilities enabling end-user safety. We verified the system's closed-loop function through a fragile egg task with vibrotactile sensory feedback. We tested the neural stimulation with an amplifier capable of eliciting transcutaneous percepts. This neuromyoelectric prosthetic system will be used for an extended take-home trial that could provide strong clinical justification for advanced, closed-loop prostheses.Clinical Relevance- This work establishes an advanced, intuitive, sensorized prosthesis that can be used in home and clinical settings.

Understanding whether pollinator behaviors and species richness drive crop yields is a key area of investigation in pollination ecology. Using sunflower as a study species we describe variation in mean floral visitation times among bee taxa and test how interactions between bee richness and the proportion of bumblebees in localized communities impact seed yield. Seven bee genera commonly visited sunflower including Agapostemon, Bombus, Halictus, Lasioglossum, Megachile, Melissodes, and Svastra. Mean visitation times to sunflower varied across genera and Bombus and Halictus spp. spent the most time foraging on inflorescences, but the number of visits by Bombus spp. was the only parameter associated with increased yields. Experimental pollination deficit reduced seed development and yields, and these effects were stronger in stands of wild-type sunflower in the field compared to a confection variety grown in the greenhouse. Relationships between bee richness and pollination services differed for potted and wild sunflower: when bees had short-term access to potted sunflower, bee richness and relative Bombus abundances were not associated with pollination quotients. When bees had long-term access to wild sunflower, relative Bombus abundances predicted pollination services but were modified by site-level bee richness: as richness increased, the effects of Bombus abundance decreased. Our studies demonstrate that bee species richness is not always a clear predictor of pollination services; instead, our results underscore the importance of specific taxa when species richness is low (here, bumblebees), and show that the effects of bee functional groups important for pollination may be modified by changes in site-level species richness., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Many animals change feeding habits as they progress through life stages, exploiting resources that vary in space and time. However, complex life histories may bring new risks if rapid environmental change disrupts the timing of these switches. Here, we use abundance times series for a diverse group of herbivorous insects, aphids, to search for trait and environmental characteristics associated with declines. Our meta dataset spanned three world regions and >300 aphid species, tracked at 75 individual sites for 10-50 years. Abundances were generally falling, with median changes of -8.3%, -5.6%, and -0.1% per year in the central USA, northwestern USA, and United Kingdom, respectively. Aphids that obligately alternated between host plants annually and those that were agricultural pests exhibited the steepest declines, relative to species able to persist on the same host plant year-round or those in natural areas. This suggests that host alternation might expose aphids to climate-induced phenology mismatches with one or more of their host plant species, with additional risks from exposure to insecticides and other management efforts. Warming temperatures through time were associated with milder aphid declines or even abundance increases, particularly at higher latitudes. Altogether, while a warming world appeared to benefit some aphid species in some places, most aphid species that had time-sensitive movements among multiple host plants seemed to face greater risk of decline. More generally, this suggests that recent human-induced rapid environmental change is rebalancing the risks and rewards associated with complex life histories., (© 2021 John Wiley & Sons Ltd.)

There is considerable interest in applying entomopathogenic fungi as a biological control to limit insect populations due to their low environmental and human applicator impacts. However, despite many promising laboratory tests, there are few examples where these fungi were successfully applied to manage bark beetles. Here, we explore how environmental conditions unique to bark beetle habitats may have limited previous entomopathogenic fungus applications, including variable temperatures, ultraviolet light, bark beetle symbiotic microorganisms, tree phytochemicals, and cryptic bark beetle behaviors. Based on the existing literature, we provide a framework for interpreting the pathogenicity of entomopathogenic fungi to bark beetles, with emphasis on both standardizing and improving laboratory approaches to enhance field applications. Our synthesis indicates that most previous laboratory evaluations are conducted under conditions that are not representative of actual bark beetle systems; this may render fungal isolates functionally non-pathogenic in field settings. We recommend that future studies place particular effort into understanding entomopathogen response to the presence of bark beetle symbiotic microorganisms, plant phytochemicals, and potential as a tree endophyte. Additionally, field application methods should aid entomopathogens in overcoming stressful conditions and allow the fungus to infect multiple bark beetle life stages. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Differences in defensive traits of tree species may predict why some conifers are susceptible to bark beetle-fungal complexes and others are not. A symbiotic fungus (Leptographium abietinum (Peck) M.J. Wingf.) associated with the tree-killing bark beetle (Dendroctonus rufipennis Kirby) is phytopathogenic to host trees and may hasten tree decline during colonization by beetles, but defense responses of mature trees to the fungus have not been experimentally examined. To test the hypothesis that interspecific variation in spruce resistance is explained by defense traits we compared constitutive (bark thickness and constitutive resin ducts) and induced defenses (resin flow, monoterpene composition, concentration, phloem lesion formation and traumatic resin ducts) between two sympatric spruces: Engelmann spruce (Picea engelmannii Parry ex Engelm.-a susceptible host) and blue spruce (Picea pungens Engelm.-a resistant host) in response to fungal inoculation. Four central findings emerged: (i) blue spruce has thicker outer bark and thinner phloem than Engelmann spruce, which may restrict fungal access to phloem and result in less beetle-available resource overall; (ii) both spruce species induce monoterpenes in response to inoculation but blue spruce has higher constitutive monoterpene levels, induces monoterpenes more rapidly, and induces higher concentrations over a period of time consistent with spruce beetle attack duration; (iii) Engelmann and blue spruce differed in the monoterpenes they upregulated in response to fungal inoculation: blue spruce upregulated α-pinene, terpinolene and γ-terpinene, but Engelmann spruce upregulated 3-carene and linalool; and (iv) blue spruce has a higher frequency of constitutive resin ducts and produces more traumatic resin ducts in annual growth increments than Engelmann spruce, though Engelmann spruce produces more resin following aseptic wounding or fungal inoculation. These findings suggest that higher constitutive resin duct densities and monoterpene concentrations, as well as the ability to rapidly induce specific monoterpenes in response to L. abietinum inoculation, are phenotypic traits associated with hosts resistant to spruce beetle colonization., (Published by Oxford University Press 2021.)

Background: Advanced prostheses can restore function and improve quality of life for individuals with amputations. Unfortunately, most commercial control strategies do not fully utilize the rich control information from residual nerves and musculature. Continuous decoders can provide more intuitive prosthesis control using multi-channel neural or electromyographic recordings. Three components influence continuous decoder performance: the data used to train the algorithm, the algorithm, and smoothing filters on the algorithm's output. Individual groups often focus on a single decoder, so very few studies compare different decoders using otherwise similar experimental conditions., Methods: We completed a two-phase, head-to-head comparison of 12 continuous decoders using activities of daily living. In phase one, we compared two training types and a smoothing filter with three algorithms (modified Kalman filter, multi-layer perceptron, and convolutional neural network) in a clothespin relocation task. We compared training types that included only individual digit and wrist movements vs. combination movements (e.g., simultaneous grasp and wrist flexion). We also compared raw vs. nonlinearly smoothed algorithm outputs. In phase two, we compared the three algorithms in fragile egg, zipping, pouring, and folding tasks using the combination training and smoothing found beneficial in phase one. In both phases, we collected objective, performance-based (e.g., success rate), and subjective, user-focused (e.g., preference) measures., Results: Phase one showed that combination training improved prosthesis control accuracy and speed, and that the nonlinear smoothing improved accuracy but generally reduced speed. Phase one importantly showed simultaneous movements were used in the task, and that the modified Kalman filter and multi-layer perceptron predicted more simultaneous movements than the convolutional neural network. In phase two, user-focused metrics favored the convolutional neural network and modified Kalman filter, whereas performance-based metrics were generally similar among all algorithms., Conclusions: These results confirm that state-of-the-art algorithms, whether linear or nonlinear in nature, functionally benefit from training on more complex data and from output smoothing. These studies will be used to select a decoder for a long-term take-home trial with implanted neuromyoelectric devices. Overall, clinical considerations may favor the mKF as it is similar in performance, faster to train, and computationally less expensive than neural networks.

Background: Electrical stimulation of residual afferent nerve fibers can evoke sensations from a missing limb after amputation, and bionic arms endowed with artificial sensory feedback have been shown to confer functional and psychological benefits. Here we explore the extent to which artificial sensations can be discriminated based on location, quality, and intensity., Methods: We implanted Utah Slanted Electrode Arrays (USEAs) in the arm nerves of three transradial amputees and delivered electrical stimulation via different electrodes and frequencies to produce sensations on the missing hand with various locations, qualities, and intensities. Participants performed blind discrimination trials to discriminate among these artificial sensations., Results: Participants successfully discriminated cutaneous and proprioceptive sensations ranging in location, quality and intensity. Performance was significantly greater than chance for all discrimination tasks, including discrimination among up to ten different cutaneous location-intensity combinations (15/30 successes, p < 0.0001) and seven different proprioceptive location-intensity combinations (21/40 successes, p < 0.0001). Variations in the site of stimulation within the nerve, via electrode selection, enabled discrimination among up to five locations and qualities (35/35 successes, p < 0.0001). Variations in the stimulation frequency enabled discrimination among four different intensities at the same location (13/20 successes, p < 0.0005). One participant also discriminated among individual stimulation of two different USEA electrodes, simultaneous stimulation on both electrodes, and interleaved stimulation on both electrodes (20/24 successes, p < 0.0001)., Conclusion: Electrode location, stimulation frequency, and stimulation pattern can be modulated to evoke functionally discriminable sensations with a range of locations, qualities, and intensities. This rich source of artificial sensory feedback may enhance functional performance and embodiment of bionic arms endowed with a sense of touch.

Livestock grazing and non-native plant species affect rangeland habitats globally. These factors may have important effects on ecosystem services including pollination, yet, interactions between pollinators, grazing, and invasive plants are poorly understood. To address this, we tested the hypothesis that cattle grazing and site colonization by cheatgrass (Bromus tectorum) impact bee foraging and nesting habitats, and the biodiversity of wild bee communities, in a shortgrass prairie system. Bee nesting habitats (litter and wood cover) were marginally improved in non-grazed sites with low cheatgrass cover, though foraging habitat (floral cover and richness, bare soil) did not differ among cattle-grazed sites or non-grazed sites with low or high cheatgrass cover. However, floral cover was a good predictor of bee abundance and functional dispersion. Mean bee abundance, richness, diversity and functional diversity were significantly lower in cattle-grazed habitats than in non-grazed habitats. Differences in bee diversity among habitats were pronounced early in the growing season (May) but by late-season (August) these differences eroded as Melissodes spp. and Bombus spp. became more abundant at study sites. Fourth-corner analysis revealed that sites with high floral cover tended to support large, social, polylectic bees; sites with high grass cover tended to support oligolectic solitary bees. Both cattle-grazed sites and sites with high cheatgrass cover were associated with lower abundances of above-ground nesting bees but higher abundance of below-ground nesters than non-grazed sites with low cheatgrass cover. We conclude that high cheatgrass cover is not associated with reduced bee biodiversity or abundance, but cattle grazing was negatively associated with bee abundances and altered species composition. Although floral cover is an important predictor of bee assemblages, this was not impacted by cattle grazing and our study suggests that cattle likely impact bee communities through effects other than those mediated by forbs, including soil disturbance or nest destruction. Efforts aimed at pollinator conservation in prairie habitats should focus on managing cattle impacts early in the growing season to benefit sensitive bee species., Competing Interests: The authors have declared that no competing interests exist.

Objective: We explore the long-term performance and stability of seven percutaneous Utah Slanted Electrode Arrays (USEAs) and intramuscular recording leads (iEMGs) implanted chronically in the residual arm nerves and muscles of three human participants as a means to permanently restore sensorimotor function after transradial amputations., Approach: We quantify the number of functional recording and functional stimulating electrodes over time. We also calculate the signal-to-noise ratio (SNR) of USEA and iEMG recordings and quantify the stimulation current necessary to evoke detectable sensory percepts. Furthermore, we quantify the consistency of the sensory modality, receptive field location, and receptive field size of USEA-evoked percepts., Main Results: In the most recent subject, involving USEAs with technical improvements, neural recordings persisted for 502 d (entire implant duration) and the number of functional recording electrodes for one USEA increased over time. However, for six out of seven USEAs across the three participants, the number of functional recording electrodes decreased within the first 2 months after implantation. The SNR of neural recordings and electromyographic recordings stayed relatively consistent over time. Sensory percepts were consistently evoked over the span of 14 months, were not significantly different in size, and highlighted the nerves' fascicular organization. The percentage of percepts with consistent modality or consistent receptive field location between sessions (∼1 month apart) varied between 0%-86.2% and 9.1%-100%, respectively. Stimulation thresholds and electrode impedances increased initially but then remained relatively stable over time., Significance: This work demonstrates improved performance of USEAs, and provides a basis for comparing the longevity and stability of USEAs to that of other neural interfaces. USEAs provide a rich repertoire of neural recordings and sensory percepts. Although their performance still generally declines over time, functionality can persist long-term. Future work should leverage the results presented here to further improve USEA design or to develop adaptive algorithms that can maintain a high level of performance.

Landscape-scale bark beetle outbreaks alter forest structure with direct and indirect effects on plants and animals in forest ecosystems. Using alpine spruce forest and a native bee community as a study system, we tested how tree mortality from bark beetles impacts bee foraging habitats and populations. Bees were collected across the growing season (early-, middle-, and late-season) for two years using passive trapping methods, and collections were used to analyze patterns in species abundances and diversity. Three important findings emerged: (1) forest stands that were post-outbreak had 62% higher floral density and 68% more floral species during peak bloom, respectively, than non-affected stands; (2) bee captures were highest early-season (June) and were not strongly affected by bark beetle outbreak; however, mean number of bee species and Shannon-Weiner diversity were significantly higher in post-outbreak stands and this effect was pronounced early in the growing season. Corresponding analysis of β-diversity indicated higher accumulation of bee biodiversity in post-outbreak stands and a turnover in the ratio of Bombus: Osmia; (3) bee captures were linked to variation in foraging habitat, but number of bee species and diversity were more strongly predicted by forest structure. Our results provide evidence of increased alpine bee biodiversity in post-outbreak stands and increased availability of floral resources. We conclude that large-scale disturbance from bark beetle outbreaks may drive shifts in pollinator community composition through cascading effects on floral resources, mediated via mortality of overstory trees.

Background: Brain activity is constrained by and evolves over a network of structural and functional connections. Corticocortical evoked potentials (CCEPs) have been used to measure this connectivity and to discern brain areas involved in both brain function and disease. However, how varying stimulation parameters influences the measured CCEP across brain areas has not been well characterized., Objective: To better understand the factors that influence the amplitude of the CCEPs as well as evoked gamma-band power (70-150 Hz) resulting from single-pulse stimulation via cortical surface and depth electrodes., Methods: CCEPs from 4370 stimulation-response channel pairs were recorded across a range of stimulation parameters and brain regions in 11 patients undergoing long-term monitoring for epilepsy. A generalized mixed-effects model was used to model cortical response amplitudes from 5 to 100 ms post-stimulation., Results: Stimulation levels <5.5 mA generated variable CCEPs with low amplitude and reduced spatial spread. Stimulation at ≥5.5 mA yielded a reliable and maximal CCEP across stimulation-response pairs over all regions. These findings were similar when examining the evoked gamma-band power. The amplitude of both measures was inversely correlated with distance. CCEPs and evoked gamma power were largest when measured in the hippocampus compared with other areas. Larger CCEP size and evoked gamma power were measured within the seizure onset zone compared with outside this zone., Conclusion: These results will help guide future stimulation protocols directed at quantifying network connectivity across cognitive and disease states., Competing Interests: Declaration of competing interest The authors confirm there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that influenced its outcome., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Traumatic meningeal enhancement (TME) is a novel biomarker observed on post-contrast fluid-attenuated inversion recovery (FLAIR) in patients who undergo contrast-enhanced magnetic resonance imaging (MRI) after suspected traumatic brain injury (TBI). TME may be seen on acute MRI despite the absence of other trauma-related intracranial findings. In this study we compare conspicuity of TME on FLAIR post-contrast and T1 weighted imaging (T1WI) post-contrast, and investigate if TME is best detected by FLAIR post-contrast or T1WI post-contrast sequences. Subjects selected for analysis enrolled in the parent study (NCT01132937) in 2016 and underwent contrast-enhanced MRI within 48 hours of suspected TBI. Two blinded readers reviewed pairs of pre- and post-contrast T1WI and FLAIR images for presence or absence of TME. Discordant pairs between the two blinded readers were reviewed by a third reader. Cohen's kappa coefficient was used to calculate agreement. Twenty-five subjects (15 males, 10 females; median age 48 (Q1:35-Q3:62; IQR: 27)) were included. The blinded readers had high agreement for presence of TME on FLAIR (Kappa of 0.90), but had no agreement for presence of TME on T1WI (Kappa of -0.24). The FLAIR and T1WI scans were compared among all three readers and 62% of the cases positive on FLAIR could be seen on T1WI. However, 38% of the cases who were read positive on FLAIR for TME were read negative for TME on T1WI. Conspicuity of TME is higher on post-contrast FLAIR MRI than on post-contrast T1WI. TME as seen on post-contrast FLAIR MRI can aid in the identification of patients with TBI., Competing Interests: The authors have declared that no competing interests exist.

Millions of people in the United States are affected by chronic pain, and the financial cost of pain treatment is weighing on the healthcare system. In some cases, current pharmacological treatments may do more harm than good, as with the United States opioid crisis. Direct electrical stimulation of the brain is one potential non-pharmacological treatment with a long history of investigation. Yet brain stimulation has been far less successful than peripheral or spinal cord stimulation, perhaps because of our limited understanding of the neural circuits involved in pain perception. In this paper, we review the history of using electrical stimulation of the brain to treat pain, as well as contemporary studies identifying the structures involved in pain networks, such as the thalamus, insula, and anterior cingulate. We propose that the thermal grill illusion, an experimental pain model, can facilitate further investigation of these structures. Pairing this model with intracranial recording will provide insight toward disentangling the neural correlates from the described anatomic areas. Finally, the possibility of altering pain perception with brain stimulation in these regions could be highly informative for the development of novel brain stimulation therapies for chronic pain.

Williams syndrome is a multisystem, congenital disorder which is commonly associated with arterial stenoses: supravalvar aortic stenosis and peripheral pulmonary artery stenosis. Venous abnormalities have not been previously reported in children with Williams syndrome. We present a case of a 3-year-old girl with Williams syndrome and diffuse venous ectasia as detected by MRI.

Sarcophyton glaucum is one of the most abundant and chemically studied soft corals with over 100 natural products reported in the literature, primarily cembrane diterpenoids. Yet, wide variation in the chemistry observed from S. glaucum over the past 50 years has led to its reputation as a capricious producer of bioactive metabolites. Recent molecular phylogenetic analysis revealed that S. glaucum is not a single species but a complex of at least seven genetically distinct species not distinguishable using traditional taxonomic criteria. We hypothesized that perceived intraspecific chemical variation observed in S. glaucum was actually due to differences between cryptic species (interspecific variation). To test this hypothesis, we collected Sarcophyton samples in Palau, performed molecular phylogenetic analysis, and prepared chemical profiles of sample extracts using gas chromatography-flame ionization detection. Both unsupervised (principal component analysis) and supervised (linear discriminant analysis) statistical analyses of these profiles revealed a strong relationship between cryptic species membership and chemical profiles. Liquid chromatography with tandem mass spectrometry-based analysis using feature-based molecular networking permitted identification of the chemical drivers of this difference between clades, including cembranoid diterpenes (2 R ,11 R ,12 R )-isosarcophytoxide ( 5 ), (2 S ,11 R ,12 R )-isosarcophytoxide ( 6 ), and isosarcophine ( 7 ). Our results suggest that early chemical studies of Sarcophyton may have unknowingly conflated different cryptic species of S. glaucum , leading to apparently idiosyncratic chemical variation.

Background: Multi-articulate prostheses are capable of performing dexterous hand movements. However, clinically available control strategies fail to provide users with intuitive, independent and proportional control over multiple degrees of freedom (DOFs) in real-time., New Method: We detail the use of a modified Kalman filter (MKF) to provide intuitive, independent and proportional control over six-DOF prostheses such as the DEKA "LUKE" arm. Input features include neural firing rates recorded from Utah Slanted Electrode Arrays and mean absolute value of intramuscular electromyographic (EMG) recordings. Ad-hoc modifications include thresholds and non-unity gains on the output of a Kalman filter., Results: We demonstrate that both neural and EMG data can be combined effectively. We also highlight that modifications can be optimized to significantly improve performance relative to an unmodified Kalman filter. Thresholds significantly reduced unintended movement and promoted more independent control of the different DOFs. Gains were significantly greater than one and served to ease movement initiation. Optimal modifications can be determined quickly offline and translate to functional improvements online. Using a portable take-home system, participants performed various activities of daily living., Comparison With Existing Methods: In contrast to pattern recognition, the MKF allows users to continuously modulate their force output, which is critical for fine dexterity. The MKF is also computationally efficient and can be trained in less than five minutes., Conclusions: The MKF can be used to explore the functional and psychological benefits associated with long-term, at-home control of dexterous prosthetic hands., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Significance: The performance of traditional approaches to decoding movement intent from electromyograms (EMGs) and other biological signals commonly degrade over time. Furthermore, conventional algorithms for training neural network based decoders may not perform well outside the domain of the state transitions observed during training. The work presented in this paper mitigates both these problems, resulting in an approach that has the potential to substantially improve the quality of life of the people with limb loss., Objective: This paper presents and evaluates the performance of four decoding methods for volitional movement intent from intramuscular EMG signals., Methods: The decoders are trained using the dataset aggregation (DAgger) algorithm, in which the training dataset is augmented during each training iteration based on the decoded estimates from previous iterations. Four competing decoding methods, namely polynomial Kalman filters (KFs), multilayer perceptron (MLP) networks, convolutional neural networks (CNN), and long short-term memory (LSTM) networks, were developed. The performances of the four decoding methods were evaluated using EMG datasets recorded from two human volunteers with transradial amputation. Short-term analyses, in which the training and cross-validation data came from the same dataset, and long-term analyses, in which the training and testing were done in different datasets, were performed., Results: Short-term analyses of the decoders demonstrated that CNN and MLP decoders performed significantly better than KF and LSTM decoders, showing an improvement of up to 60% in the normalized mean-square decoding error in cross-validation tests. Long-term analyses indicated that the CNN, MLP, and LSTM decoders performed significantly better than a KF-based decoder at most analyzed cases of temporal separations (0-150 days) between the acquisition of the training and testing datasets., Conclusion: The short-term and long-term performances of MLP- and CNN-based decoders trained with DAgger demonstrated their potential to provide more accurate and naturalistic control of prosthetic hands than alternate approaches.